When to treat hypercholesterolaemia

Pedro-Botet, Juan; Climent, Elisenda; Benaiges, David; Llauradó, Gemma
doi:10.1016/j.medcle.2023.09.019
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cholesterol is an essential molecule for modulating the fluidity of cell membranes&#44; the function of cellular transporters and intracellular signalling systems&#59; it is also a precursor of myelin&#44; bile salts&#44; vitamin D&#44; steroid hormones and plays a key role in maintaining skin impermeability&#46; All somatic cells&#44; including astrocytes and oligodendrocytes&#44; synthesise cholesterol via the same pathway used by the liver&#44; even when the plasma concentration of low-density lipoprotein &#40;LDL-C&#41; cholesterol is extremely low&#59; in addition&#44; they can obtain small amounts of cholesterol from high-density lipoprotein &#40;HDL&#41;&#46; In fact&#44; no tissue relies on cholesterol transfer from LDL-C&#59; thus&#44; the ovaries&#44; testes and adrenal cortex produce cholesterol de <span class="elsevierStyleItalic">novo</span> or import it from HDL particles via SR-B1 receptors&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Moreover&#44; the human body is unable to metabolise cholesterol because it cannot break down its central skeleton made up of the cyclopentanoperhydrophenanthrene ring&#44; which highlights the importance of cholesterol homeostasis through the balance between endogenous synthesis&#44; intestinal absorption and bile acid excretion&#46; This undoubtedly justifies the interest in the mechanisms of cholesterol synthesis and intestinal absorption as therapeutic targets for reducing cholesterolaemia&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Hypercholesterolaemia and the resulting accumulation of cholesterol in tissues such as the sclera&#44; dermis and tendons&#44; but mainly in the arterial wall&#44; can lead to serious clinical complications&#46; In this regard&#44; cardiovascular disease &#40;CVD&#41;&#44; especially coronary heart disease and atherothrombotic ischaemic stroke&#44; is the leading cause of mortality worldwide and a major factor in disability&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Cholesterol as an aetiological agent of atherosclerosis</span><p id="par0020" class="elsevierStylePara elsevierViewall">Since the description in 1913 of the relationship between hypercholesterolaemia and atherosclerosis by Anichkow when rabbits were fed a cholesterol-rich diet&#44; the pathophysiological understanding of atherosclerosis has advanced considerably&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> concluding that LDL-C is a vascular toxicant&#46; LDL particles are the end product of lipoprotein metabolism&#44; and their main route of elimination is via LDL receptors&#59; when the number of particles is excessive or they are small in size&#44; they are deposited by transcytosis in the arterial wall intima and taken up by macrophages&#46; At this level&#44; LDL particles cause endothelial dysfunction and stimulate inflammatory phenomena and cell proliferation in the vascular wall&#46; According to the Cholesterol Treatment Trialist Collaboration&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> the reduction in cardiovascular risk associated with statin therapy is due to the absolute decrease in serum LDL-C concentrations&#46; Likewise&#44; LDL-C reduction mediated by other drugs such as ezetimibe or proprotein convertase subtilisin&#47;kexin type 9 &#40;PCSK9&#41; inhibitors or even by non-pharmacological interventions such as diet or ileal bypass surgery result in the same risk reduction per unit of reduced LDL-C&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> This association has been corroborated by Mendelian randomisation studies<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and persists for subclinical disease according to the findings of the Progression of Early Subclinical Atherosclerosis &#40;PESA&#41; study&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Modern intravascular ultrasound regression studies using novel image analysis techniques have shown that achieving low LDL-C levels with combined statin and PCSK9 inhibitor therapy is linked to beneficial effects on plaque composition together with a decrease in atherosclerotic burden<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#59; therefore&#44; in this clinical scenario&#44; we are performing an aetiological treatment of the disease&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Cholesterol and clinical guidelines</span><p id="par0030" class="elsevierStylePara elsevierViewall">The foregoing explains why LDL-C is considered the main therapeutic target in cardiovascular prevention by the clinical guidelines for the management of dyslipidaemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;13</span></a> These are a set of recommendations based on the systematic review of the available evidence and on the evaluation of the different alternatives to optimise patient care&#44; providing algorithms&#44; calculators and risk charts&#46; However&#44; the recommendations issued by the different clinical guidelines reveal similarities in many aspects and relevant discrepancies in others&#46; The main sources of variation are differences in cardiovascular risk according to ethnicity but&#44; surprisingly&#44; they come to different conclusions despite evaluating the same scientific evidence&#46; In addition&#44; most clinical guidelines are not without limitations&#44; including inadequate personalisation of care&#44; slow incorporation of new knowledge&#44; relatively conservative therapeutic strategies&#44; and being too long and complex&#44; which makes them unattractive to many professionals and therefore under-consulted&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Current guidelines stress the need to achieve LDL-C targets in adults over 40 years of age at high&#47;very high cardiovascular risk&#46; However&#44; it should not be forgotten that clinical complications start at an earlier age&#44; with approximately half of all cardiovascular events occurring before the age of 65 years&#44; and a quarter as a form of presentation in males under 55 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Furthermore&#44; early diagnosis of familial hypercholesterolaemia &#40;FH&#41; and other monogenic dyslipidaemias with high cardiovascular risk is necessary in order to initiate treatment at an early age&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Recommendations on cholesterolaemia management in adults aged 20&#8211;40 years without FH&#44; diabetes mellitus&#44; chronic kidney disease or CVD from the National Lipid Association&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> American College of Cardiology&#47;American Heart Association &#40;ACC&#47;AHA&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> European Society of Cardiology&#47;European Atherosclerosis Society<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> &#40;ESC&#47;EAS&#41; or the Canadian Cardiovascular Society<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> are less robust &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Focusing on the ESC&#47;EAS 2019 guidelines<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> for the management of dyslipidaemia&#44; the indication for therapy with HMG-CoA reductase inhibitors or statins in patients aged 40 years and older is based on the 10-year cardiovascular risk&#44; estimated using the Systematic COronary Risk Evaluation &#40;SCORE2&#41; prediction algorithm&#46; Although the guidelines do not provide a risk prediction for those under 40&#44; it includes a relative risk figure for younger individuals&#44; highlighting possible changes with increasing cholesterolaemia and blood pressure&#46; The European guidelines recommend lifestyle modification for younger patients with elevated cardiovascular risk but does not provide specific guidance on the use of lipid-lowering drugs for those under 40 without FH&#44; diabetes or chronic kidney disease&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">According to the World Health Organisation &#40;WHO&#41;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> the global prevalence of total cholesterolaemia &#8805;190&#8239;mg&#47;dL in people over 18 years of age as of 2008 is close to 40&#37;&#46; In the general Spanish population&#44; the prevalence is between 30 and 50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> It should be noted that LDL-C concentrations measured before adulthood predict the risk of CVD or subclinical atherosclerosis&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> On the other hand&#44; some studies have shown that clinical guidelines would not have recommended lipid-lowering therapy for at least half of the patients who subsequently present with premature myocardial infarction&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> This explains&#44; at least in part&#44; the underuse of statins in young adults with moderately elevated LDL-C in actual clinical practice&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The risks and benefits of early lipid-lowering therapy in younger hypercholesterolaemic adults without CVD&#44; FH&#44; diabetes or renal dysfunction&#44; a clinical scenario not specifically addressed in current clinical practice guidelines&#44; are discussed below&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Atherosclerosis starts early in life</span><p id="par0060" class="elsevierStylePara elsevierViewall">Atherosclerosis is a chronic disease that begins in early childhood and&#44; without intervention&#44; progresses and inevitably worsens throughout life&#44; sometimes at an accelerated rate&#46; The initiator of atherogenesis is the deposition of apolipoprotein &#40;apo&#41; B-containing lipoproteins&#44; including LDL&#44; in the subendothelial space&#46; In the absence of lipid deposition in the arterial wall&#44; there is little or no inflammation and no atherosclerosis&#46; In other words&#44; without LDL-C there is no atherosclerosis&#44; so the course of the disease is modifiable and even reversible&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Necropsy studies have documented atherosclerotic lesions in the coronary tree of young adults killed in the Korean War&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> as well as in young victims &#40;12&#8211;35 years&#41; of traumatic causes&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> The lasting effect of elevated LDL-C on the progression of atherosclerosis is illustrated by individuals with FH who&#44; exposed to very high LDL-C concentrations from birth&#44; develop cardiovascular complications before the age of 15 in the homozygous form and in young adulthood in the heterozygous form if they do not receive lipid-lowering drug treatment&#46; In contrast&#44; carriers of certain genetic mutations that cause low LDL-C levels are protected from CVD&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Lifestyle changes are beneficial&#44; but&#8230;</span><p id="par0070" class="elsevierStylePara elsevierViewall">If LDL-C could be maintained below the recommended targets by a healthy lifestyle alone&#44; the benefit would be immense&#46; In this regard&#44; we refer the reader to the national evidence on the Mediterranean diet from the PREDIMED and CORDIOPREV studies in primary and secondary prevention of CVD&#44; respectively&#46; However&#44; the current rates of childhood obesity and metabolic syndrome generate an inevitable scepticism in the ability to correct and&#47;or improve the lifestyle of industrialised societies&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">As with other cardiovascular risk factors&#44; such as smoking&#44; high blood pressure or diabetes&#44; the fact that it is not only the concentration of cholesterol&#44; but also the cumulative exposure time&#44; provides a positive incentive to optimise current strategies&#46; Moreover&#44; we must bear in mind that the delay in treatment will continue to expose younger people to an <span class="elsevierStyleItalic">a priori</span> avoidable risk&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Benefits&#47;risks of early statin therapy</span><p id="par0080" class="elsevierStylePara elsevierViewall">The epidemic of diabesity and poor control of LDL-C targets according to cardiovascular risk mean that CVD will continue to be a major health problem&#59; therefore&#44; early initiation of lipid-lowering therapy could reduce the burden of CVD and enhance the benefits in those at highest risk&#46; Although economic data on statin therapy in adults under 40 years of age are limited&#44; a simulated analysis of the impact of statins in subjects aged 18&#8211;39 years with an LDL-C concentration &#62;130&#8239;mg&#47;dL suggested that it would be highly cost-effective in men and moderately cost-effective in women in preventing or delaying cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Since the approval of lovastatin in 1987 for use in humans&#44; statins have demonstrated an excellent safety profile&#46; Although there are no long-term data in young people&#44; evidence accumulated with statins in adults over the past decades confirms that they are safe and well tolerated&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Pharmacovigilance studies in children with FH have also shown no adverse effects&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Statin-associated muscle symptoms &#40;SAMS&#41;&#44; described in up to 30&#37; of people treated with statins&#44; are a common reason for non-adherence and discontinuation of treatment&#46; At this point it is worth mentioning that randomised controlled clinical trials have found no difference in the frequency of muscle symptoms between the active statin treatment group and the placebo group&#44; suggesting a nocebo effect&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> SAMS tend to be more common in older adults&#44; so they do not usually represent a barrier to statin use in younger people&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The possibility of pregnancy is also a factor in the young woman of childbearing age&#46; Classically&#44; statins have been denied to pregnant women or women who might become pregnant due to the theoretical risk of teratogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> In 2021&#44; the Food and Drug Administration &#40;FDA&#41; withdrew this contraindication in the absence of relevant data on statin-related birth defects and recommends continuing statins in women who could become pregnant but discontinuing them during pregnancy and lactation in all but those at very high cardiovascular risk&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Complementary strategies for LDL-C reduction</span><p id="par0100" class="elsevierStylePara elsevierViewall">The conceptual goal of lipid-lowering therapy is to reduce cardiovascular risk by lowering LDL-C to a plasma concentration that prevents the onset&#44; progression or complication of atherosclerotic CVD&#46; This will most likely lead to earlier treatment and lower LDL-C concentrations &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; To identify and treat these individuals earlier&#44; even though their absolute risk may be low&#44; we present below a number of complementary strategies to help manage hypercholesterolaemia&#44; from the more traditional to the more innovative&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Use of cardiovascular risk stratification tools</span><p id="par0105" class="elsevierStylePara elsevierViewall">The current European recommendation for initiation of statin therapy based on estimated 10-year cardiovascular risk from the age of 40 does not facilitate early intervention&#44; when the potential for risk reduction is greatest&#46; For this reason&#44; a 30-year cardiovascular risk estimation model has been designed&#46; Retrospective studies of the applicability of this model have shown considerable progress in predicting clinical events leading to earlier statin use and lower cardiovascular risk in younger individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Estimating lifetime cardiovascular risk is another method of risk stratification&#46; Most young adults considered to be at low or moderate cardiovascular risk with current 10-year risk charts would probably become high-risk if risk were considered over a longer period&#44; such as over the remaining years of life&#46; In this regard&#44; several calculators have been designed to estimate lifetime cardiovascular risk such as the QRISK-LTR equation in the UK or the one developed by the ACC&#47;AHA&#46; More recently&#44; the European guidelines on cardiovascular prevention 2021<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> provided applications for its estimation &#40;LIFE-CVD&#41;&#44; as well as the benefits of treatment in terms of CVD-free life-years gained&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Other tools to improve the identification of young patients most likely to benefit from early treatment lie in imaging or biomarkers&#46; Among the former&#44; coronary artery calcium &#40;CAC&#41; quantification with computed tomography is useful to identify patients at high cardiovascular risk by providing direct evidence of atherosclerotic disease&#46; CAC burden is a strong predictor of cardiovascular events independently of other risk factors&#46; However&#44; the following points should be made&#46; Plaque calcification occurs at advanced stages and therefore does not achieve detection prior to plaque formation&#46; In fact&#44; non-calcified plaque has a high probability of causing intra-arterial thrombosis and has been reported to be present in patients with a CAC score of 0&#46; In the middle-aged and older population&#44; the absence of CAC may be reassuring&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> However&#44; in younger patients who have had less time to develop calcified plaques&#44; the absence of CAC should be interpreted with caution&#46; Indeed&#44; the predictive value of CAC for obstructive coronary artery disease in adults older than 18 years varied by age group&#44; being less predictive in those younger than 40 years and more predictive in those older than 70 years&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> In conclusion&#44; while the presence of CAC in younger patients is highly predictive of CVD&#44; and even more powerful than in older patients&#44; a CAC score of zero in this population should be viewed with caution&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Among the biomarkers for improved cardiovascular risk stratification&#44; lipoprotein&#40;a&#41; &#91;Lp&#40;a&#41;&#93;&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> an LDL particle with a specific apo&#44; apo&#40;a&#41;&#44; bound by a disulfide bridge to apo B&#44; must be mentioned&#46; Scientific evidence from observational&#44; Mendelian randomisation and genome-wide association studies has confirmed that elevated Lp&#40;a&#41; is associated with an increased risk of CVD independently of LDL-C&#44; although the precise mechanism is unknown&#46; Lp&#40;a&#41; concentration is genetically determined and remains stable throughout life&#46; Although Lp&#40;a&#41; concentration is refractory to statin therapy&#44; statin therapy in those with elevated Lp&#40;a&#41; is associated with a decrease in cardiovascular risk&#46; Several therapies are currently in development to reduce elevated Lp&#40;a&#41; levels&#46; Lp&#40;a&#41; quantification in young adults should be considered to identify individuals who have inherited an extremely elevated Lp&#40;a&#41; level &#8805;180&#8239;mg&#47;dL &#40;&#8805;430&#8239;nmol&#47;L&#41; and therefore have a very high lifetime cardiovascular risk&#44; equivalent to the risk associated with heterozygous FH&#46; In addition&#44; this strategy allows the identification of individuals with less extreme Lp&#40;a&#41; elevations who may be at higher risk than that reflected in the SCORE charts and should prompt a more aggressive approach to LDL-C reduction&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Early&#44; potent and intermittent LDL-C lowering strategy</span><p id="par0125" class="elsevierStylePara elsevierViewall">Long-term follow-up of several statin intervention studies in primary prevention provides evidence of a &#34;legacy&#34; effect based on the fact that early and potent LDL-C reduction has a long-lasting and beneficial impact on plaque stabilisation&#44; atherosclerotic burden and risk of cardiovascular events&#46; Thus&#44; participants treated with statins for three to five years continue to have a lower cardiovascular risk over clinical follow-up periods of 11&#8211;20 years&#46; Proponents of this strategy have suggested an initial three-year period of high-intensity cholesterol-lowering therapy aimed at achieving an LDL-C concentration between 20 and 40&#8239;mg&#47;dL&#44; which could be repeated periodically every 10 years to maintain a low plaque burden&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> However&#44; further studies are needed to determine the optimal therapeutic duration needed to stimulate regression&#44; as well as the minimum interval between treatment periods&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Polygenic risk charts</span><p id="par0130" class="elsevierStylePara elsevierViewall">Experts in CVD genetics argue that non-familial forms are mainly related to a combination of common variants with a small effect distributed across the genome and rare variants of moderate effect located in genes known to cause familial forms of the disease&#46; The concept of a polygenic risk score emerged shortly after large-scale genome-wide association studies &#40;GWAS&#41; made progress in identifying genomic <span class="elsevierStyleItalic">loci</span> for CVD-related traits&#44; with the observation that carriers of more risk alleles had a markedly increased risk of cardiovascular events&#46; Although the number of studies with polygenic risk estimates has grown exponentially in recent years&#44; their clinical utility remains limited&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Polygenic risk scores have shown modestly improved predictive ability in the adult population compared to conventional risk assessment and were predictive of response to statins in certain subgroups&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;32</span></a> Overall&#44; it is to be expected that as polygenic risk scores evolve and GWAS cohorts increase in size and diversity&#44; these scores will provide additional predictive value to current cardiovascular risk charts&#44; especially in younger age groups&#46; Their predictive value and cost-effectiveness will need to be carefully assessed for each age group in order to optimise their clinical utility&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Gene editing</span><p id="par0135" class="elsevierStylePara elsevierViewall">Although genetic variants were initially speculated to be non-modifiable and deterministic&#44; the advent of DNA editing technology in 2012 brought with it the potential for genetic correction of monogenic conditions&#44; including CVD&#46; Thus&#44; interest has grown in the application of gene editing to permanently alter genes involved in cholesterol metabolism&#44; obviating the need for future drug therapy&#46; Gene editing tools based on CRISPR-Cas9 and Clustered Regularly Interspaced Short Palindromic Repeats &#40;CRISPR&#41; have the capacity to permanently alter the genome of target tissues&#46; A preclinical study in primates with CRISPR base editors targeting the PCSK9 gene resulted in a decrease in PCSK9 concentration of 90 and 60&#37; in LDL-C after a single infusion and was sustained for at least eight months&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> This experimental study provided the basis for the construction of the human PCSK9 gene-targeted CRISPR base-editing VERVE-101&#44; recently approved for a first-in-human phase 1 clinical trial&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">With regard to hypercholesterolaemia and bearing in mind the <span class="elsevierStyleItalic">continuum</span> of cardiovascular risk on the horizon&#44; when a patient presents with a cardiovascular event&#44; whether coronary or extra-coronary&#44; he or she is in the realm of secondary prevention&#59; this should be interpreted pathophysiologically as a primary prevention failure&#46; Lowering LDL-C to the lowest possible level in people with CVD&#44; advanced subclinical atherosclerosis&#44; myocardial dysfunction&#44; diabetes or renal failure should be considered as the primary aetiological treatment of atherosclerotic disease&#44; not as true prevention&#46; Admittedly&#44; the emphasis of cardiovascular prevention is on treatment from the fourth&#47;fifth decade of life&#44; when there is an advanced disease burden&#46; In this article&#44; we support the hypothesis that LDL-C-lowering therapy earlier in the life course&#44; when atherosclerosis is less severe and more reversible&#44; may be the ideal strategy for effective cardiovascular prevention &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">&#34;Life has no price&#44; but it does have a cost&#34;&#44; and this tends to dominate health policy decisions&#46; Despite advances in our ability to modify cardiovascular risk&#44; there is still a lot of debate about the optimal way to treat adults under 40 years of age with elevated LDL-C without associated comorbidities&#46; We believe that in the not-too-distant future we will have clinical trials that will clarify which young adults should have their LDL-C aggressively lowered&#44; at what age&#44; to what level and with what therapies&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Funding</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have not received any funding for the preparation of this article&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interest</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors had no conflict of interest in the preparation of this article&#46;</p></span></span>"
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          "titulo" => "Cholesterol as an aetiological agent of atherosclerosis"
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          "titulo" => "Lifestyle changes are beneficial&#44; but&#8230;"
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          "titulo" => "Benefits&#47;risks of early statin therapy"
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          "titulo" => "Complementary strategies for LDL-C reduction"
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          "titulo" => "Use of cardiovascular risk stratification tools"
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          "titulo" => "Early&#44; potent and intermittent LDL-C lowering strategy"
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          "titulo" => "Polygenic risk charts"
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          "titulo" => "Gene editing"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ACC&#47;AHA&#58; American College of Cardiology&#47;American Heart Association&#59; CCS&#58; Canadian Cardiovascular Society&#59; CLEM&#58; cardiovascular life expectancy model&#59; CVR&#58; cardiovascular risk&#59; CVD&#58; cardiovascular disease&#59; ESC&#47;EAS&#58; European Society of Cardiology&#47;European Atherosclerosis Society&#59; FH&#58; familial hypercholesterolaemia&#59; FRS&#58; Framigham risk score&#59; LDL-C&#58; low-density lipoprotein cholesterol&#59; NLA&#58; National Lipid Association&#59; SBP&#58; systolic blood pressure&#46;</p>"
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RCV estimation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Assess lifetime CVR&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Assess 30-year or lifetime CVR with the pooled cohort equation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Assess lifetime CVR or relative 10-year risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Assess CVR with validated models &#40;FRS or CLEM&#41;&#46; In subjects aged 30&#8722;59 years without DM&#44; the presence of early CVD in first-degree relatives increases the individual CVR estimated by FRS by almost twofold&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Therapeutic strategy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No age-specific recommendation&#46; First-line statin therapy for all those with therapeutic indication&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lifestyle modification&#46;Consider lipid-lowering therapy if LDL-C &#8805; 160&#8239;mg&#47;dL and familial history of premature CVD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lifestyle recommendations&#46;Lipid-lowering treatment is only considered in the presence of FH or other risk factors&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No age-specific recommendation&#46;In primary prevention&#44; statin therapy according to CVR&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Recommendations from major clinical guidelines on the management of hypercholesterolaemia in adults aged 20-40 years without familial hypercholesterolaemia&#44; diabetes&#44; chronic kidney disease or cardiovascular disease&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:33 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and pathophysiological evidence supporting the safety of extremely low LDL levels &#8211; the zero-LDL hypothesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Masana"
                            1 => "J&#46; Girona"
                            2 => "D&#46; Ibarretxe"
                            3 => "R&#46; Rodr&#237;guez-Calvo"
                            4 => "R&#46; Rosales"
                            5 => "J&#46;C&#46; Vallv&#233;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacl.2017.12.018"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Lipidol&#46;"
                        "fecha" => "2018"
                        "volumen" => "12"
                        "paginaInicial" => "292"
                        "paginaFinal" => "299"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29398429"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global burden of cardiovascular diseases and risk factors&#44; 1990-2019&#58; update from the GBD 2019 study"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;A&#46; Roth"
                            1 => "G&#46;A&#46; Mensah"
                            2 => "C&#46;O&#46; Johnson"
                            3 => "G&#46; Addolorato"
                            4 => "E&#46; Ammirati"
                            5 => "L&#46;M&#46; Baddour"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2020.11.010"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol&#46;"
                        "fecha" => "2020"
                        "volumen" => "76"
                        "paginaInicial" => "2982"
                        "paginaFinal" => "3021"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33309175"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low-density lipoproteins cause atherosclerotic cardiovascular disease&#46; 1&#46; Evidence from genetic&#44; epidemiologic&#44; and clinical studies&#46; A consensus statement from the European Atherosclerosis Society Consensus Panel"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;A&#46; Ference"
                            1 => "H&#46;N&#46; Ginsberg"
                            2 => "I&#46; Graham"
                            3 => "K&#46;K&#46; Ray"
                            4 => "C&#46;J&#46; Packard"
                            5 => "E&#46; Bruckert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehx144"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J&#46;"
                        "fecha" => "2017"
                        "volumen" => "38"
                        "paginaInicial" => "2459"
                        "paginaFinal" => "2472"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28444290"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low-density lipoproteins cause atherosclerotic cardiovascular disease&#58; pathophysiological&#44; genetic&#44; and therapeutic insights&#58; a consensus statement from the European Atherosclerosis Society Consensus Panel"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Bor&#233;n"
                            1 => "M&#46;J&#46; Chapman"
                            2 => "R&#46;M&#46; Krauss"
                            3 => "C&#46;J&#46; Packard"
                            4 => "J&#46;F&#46; Bentzon"
                            5 => "C&#46;J&#46; Binder"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehz962"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J&#46;"
                        "fecha" => "2020"
                        "volumen" => "41"
                        "paginaInicial" => "2313"
                        "paginaFinal" => "2330"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32052833"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of LDL-lowering therapy among men and women&#58; meta-analysis of individual data from 174&#44;000 participants in 27 randomised trials"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "Cholesterol Treatment Trialists&#8217; &#40;CTT&#41; Collaboration"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Fulcher"
                            1 => "R&#46; O&#8217;Connell"
                            2 => "M&#46; Voysey"
                            3 => "J&#46; Emberson"
                            4 => "L&#46; Blackwell"
                            5 => "B&#46; Mihaylova"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(14)61368-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2015"
                        "volumen" => "385"
                        "paginaInicial" => "1397"
                        "paginaFinal" => "1405"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25579834"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;G&#46; Silverman"
                            1 => "B&#46;A&#46; Ference"
                            2 => "K&#46; Im"
                            3 => "S&#46;D&#46; Wiviott"
                            4 => "R&#46;P&#46; Giugliano"
                            5 => "S&#46;M&#46; Grundy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "JAMA&#46;"
                        "fecha" => "2016"
                        "volumen" => "316"
                        "paginaInicial" => "1289"
                        "paginaFinal" => "1297"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Progression of early subclinical atherosclerosis &#40;PESA&#41; study&#58; JACC focus seminar 7&#47;8"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "B&#46; Ibanez"
                            1 => "A&#46; Fern&#225;ndez-Ortiz"
                            2 => "L&#46; Fern&#225;ndez-Friera"
                            3 => "I&#46; Garc&#237;a-Lunar"
                            4 => "V&#46; Andr&#233;s"
                            5 => "V&#46; Fuster"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2021.05.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol&#46;"
                        "fecha" => "2021"
                        "volumen" => "78"
                        "paginaInicial" => "156"
                        "paginaFinal" => "179"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34238438"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intensive lipid lowering agents and coronary atherosclerosis&#58; insights from intravascular imaging"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46; Di Giovanni"
                            1 => "S&#46;J&#46; Nicholls"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Am J Prev Cardiol&#46;"
                        "fecha" => "2022"
                        "volumen" => "11"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "National Lipid Association recommendations for patient-centered management of dyslipidemia&#58; part 1-full report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;A&#46; Jacobson"
                            1 => "M&#46;K&#46; Ito"
                            2 => "K&#46;C&#46; Maki"
                            3 => "C&#46;E&#46; Orringer"
                            4 => "H&#46;E&#46; Bays"
                            5 => "P&#46;H&#46; Jones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacl.2015.02.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Lipidol&#46;"
                        "fecha" => "2015"
                        "volumen" => "9"
                        "paginaInicial" => "129"
                        "paginaFinal" => "169"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25911072"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "National Lipid Association recommendations for patient-centered management of dyslipidemia&#58; part 2"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "NLA Expert Panel"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;A&#46; Jacobson"
                            1 => "K&#46;C&#46; Maki"
                            2 => "C&#46;E&#46; Orringer"
                            3 => "P&#46;H&#46; Jones"
                            4 => "P&#46; Kris-Etherton"
                            5 => "G&#46; Sikand"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacl.2015.09.002"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Lipidol"
                        "fecha" => "2015"
                        "volumen" => "9"
                        "numero" => "Suppl&#46;6"
                        "paginaInicial" => "S1"
                        "paginaFinal" => "122"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26699442"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2018 AHA&#47;ACC&#47;AACVPR&#47;AAPA&#47;ABC&#47;ACPM&#47;ADA&#47;AGS&#47;APhA&#47;ASPC&#47;NLA&#47;PCNA guideline on the management of blood cholesterol&#58; a report of the American College of Cardiology&#47;American Heart Association Task Force on Clinical Practice Guidelines"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;M&#46; Grundy"
                            1 => "N&#46;J&#46; Stone"
                            2 => "A&#46;L&#46; Bailey"
                            3 => "C&#46; Beam"
                            4 => "K&#46;K&#46; Birtcher"
                            5 => "R&#46;S&#46; Blumenthal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIR.0000000000000625"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation&#46;"
                        "fecha" => "2019"
                        "volumen" => "139"
                        "paginaInicial" => "e1082"
                        "paginaFinal" => "143"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30586774"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2019 ESC&#47;EAS guidelines for the management of dyslipidaemias&#58; lipid modification to reduce cardiovascular risk"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "ESC Scientific Document Group"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Mach"
                            1 => "C&#46; Baigent"
                            2 => "A&#46;L&#46; Catapano"
                            3 => "K&#46;C&#46; Koskinas"
                            4 => "M&#46; Casula"
                            5 => "L&#46; Badimon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehz455"
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                        "tituloSerie" => "Eur Heart J&#46;"
                        "fecha" => "2020"
                        "volumen" => "41"
                        "paginaInicial" => "111"
                        "paginaFinal" => "188"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31504418"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2021 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in adults"
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                          "etal" => true
                          "autores" => array:6 [
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                            2 => "T&#46;J&#46; Anderson"
                            3 => "A&#46;R&#46; Barry"
                            4 => "P&#46; Couture"
                            5 => "N&#46; Dayan"
                          ]
                        ]
                      ]
                    ]
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                        "paginaFinal" => "1150"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33781847"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of premature cardiovascular disease vs the number of premature cardiovascular events"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;D&#46; Sniderman"
                            1 => "G&#46; Thanassoulis"
                            2 => "K&#46; Williams"
                            3 => "M&#46; Pencina"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamacardio.2016.0991"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA Cardiol&#46;"
                        "fecha" => "2016"
                        "volumen" => "1"
                        "paginaInicial" => "492"
                        "paginaFinal" => "494"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27438330"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization&#46; Noncommunicable diseases&#58; risk factors 2021 &#91;accessed 8 junio 2023&#93;&#46; Available from&#58; <a target="_blank" href="https://www.who.int/data/gho/data/themes/topics/noncommunicable-diseases-risk-factors">https&#58;&#47;&#47;www&#46;who&#46;int&#47;data&#47;gho&#47;data&#47;themes&#47;topics&#47;noncommunicable-diseases-risk-factors</a>&#46;"
                ]
              ]
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            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Situaci&#243;n actual de la dislipemia en Espa&#241;a&#58; la visi&#243;n del cardi&#243;logo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Cordero"
                            1 => "L&#46; F&#225;cila"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Esp Cardiol Supl&#46;"
                        "fecha" => "2015"
                        "volumen" => "15"
                        "paginaInicial" => "2"
                        "paginaFinal" => "7"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early contributors to healthy arterial aging versus premature atherosclerosis in young adults&#58; the Bogalusa Heart Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;C&#46; Razavi"
                            1 => "L&#46;A&#46; Bazzano"
                            2 => "J&#46; He"
                            3 => "M&#46; Krousel-Wood"
                            4 => "J&#46; Chen"
                            5 => "C&#46; Fernandez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Am Heart Assoc&#46;"
                        "fecha" => "2021"
                        "volumen" => "10"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Performance of guideline recommendations for prevention of myocardial infarction in young adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Zeitouni"
                            1 => "M&#46;G&#46; Nanna"
                            2 => "J&#46;L&#46; Sun"
                            3 => "K&#46; Chiswell"
                            4 => "E&#46;D&#46; Peterson"
                            5 => "A&#46;M&#46; Navar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Coll Cardiol&#46;"
                        "fecha" => "2020"
                        "volumen" => "76"
                        "paginaInicial" => "653"
                        "paginaFinal" => "664"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Landmark article&#44; July 18&#44; 1953&#58; coronary disease among United States soldiers killed in action in Korea&#46; Preliminary report&#46; By William F&#46; Enos&#44; Robert H&#46; Holmes and James Beyer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "W&#46;F&#46; Enos"
                            1 => "R&#46;H&#46; Holmes"
                            2 => "J&#46; Beyer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.256.20.2859"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "1986"
                        "volumen" => "256"
                        "paginaInicial" => "2859"
                        "paginaFinal" => "2862"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3534336"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Preclinical coronary atherosclerosis in a population with low incidence of myocardial infarction&#58; cross sectional autopsy study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Bertomeu"
                            1 => "O&#46; Garc&#237;a-Vidal"
                            2 => "X&#46; Farr&#233;"
                            3 => "A&#46; Galobart"
                            4 => "M&#46; V&#225;zquez"
                            5 => "J&#46;C&#46; Laguna"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmj.327.7415.591"
                      "Revista" => array:6 [
                        "tituloSerie" => "BMJ&#46;"
                        "fecha" => "2003"
                        "volumen" => "327"
                        "paginaInicial" => "591"
                        "paginaFinal" => "592"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12969923"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cost-effectiveness of lipid-lowering treatments in young adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;N&#46; Kohli-Lynch"
                            1 => "B&#46;K&#46; Bellows"
                            2 => "Y&#46; Zhang"
                            3 => "B&#46; Spring"
                            4 => "D&#46;S&#46; Kazi"
                            5 => "M&#46;J&#46; Pletcher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Coll Cardiol&#46;"
                        "fecha" => "2021"
                        "volumen" => "78"
                        "paginaInicial" => "1954"
                        "paginaFinal" => "1964"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Statin-associated muscle symptoms&#58; beware of the nocebo effect"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46; Pedro-Botet"
                            1 => "J&#46; Rubi&#233;s-Prat"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet&#46;"
                        "fecha" => "2017"
                        "volumen" => "389"
                        "paginaInicial" => "2445"
                        "paginaFinal" => "2446"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Statin use in pregnancy&#58; is it time for a paradigm shift&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Mauricio"
                            1 => "A&#46; Khera"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.121.058983"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation&#46;"
                        "fecha" => "2022"
                        "volumen" => "145"
                        "paginaInicial" => "496"
                        "paginaFinal" => "498"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35157518"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The expected 30-year benefits of early versus delayed primary prevention of cardiovascular disease by lipid lowering"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;J&#46; Pencina"
                            1 => "K&#46;M&#46; Pencina"
                            2 => "D&#46; Lloyd-Jones"
                            3 => "A&#46;L&#46; Catapano"
                            4 => "G&#46; Thanassoulis"
                            5 => "A&#46;D&#46; Sniderman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Circulation&#46;"
                        "fecha" => "2020"
                        "volumen" => "130"
                        "paginaInicial" => "827"
                        "paginaFinal" => "837"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2021 ESC guidelines on cardiovascular disease prevention in clinical practice"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "ESC National Cardiac Societies&#59; ESC Scientific Document Group"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;L&#46;J&#46; Visseren"
                            1 => "F&#46; Mach"
                            2 => "Y&#46;M&#46; Smulders"
                            3 => "D&#46; Carballo"
                            4 => "K&#46;C&#46; Koskinas"
                            5 => "M&#46; B&#228;ck"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehab484"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J&#46;"
                        "fecha" => "2021"
                        "volumen" => "42"
                        "paginaInicial" => "3227"
                        "paginaFinal" => "3337"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34458905"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coronary artery calcium versus pooled cohort equations score for primary prevention guidance&#58; randomized feasibility trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;B&#46; Muhlestein"
                            1 => "K&#46;U&#46; Knowlton"
                            2 => "V&#46;T&#46; Le"
                            3 => "D&#46;L&#46; Lappe"
                            4 => "H&#46;T&#46; May"
                            5 => "D&#46;B&#46; Min"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jcmg.2021.11.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "JACC Cardiovasc Imaging&#46;"
                        "fecha" => "2022"
                        "volumen" => "15"
                        "paginaInicial" => "843"
                        "paginaFinal" => "855"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34922872"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association of age with the diagnostic value of coronary artery calcium score for ruling out coronary stenosis in symptomatic patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "S&#46; Gaur"
                            2 => "A&#46; Frimmer"
                            3 => "H&#46;E&#46; B&#248;tker"
                            4 => "H&#46;T&#46; S&#248;rensen"
                            5 => "K&#46;H&#46; Kragholm"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamacardio.2021.4406"
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                        "tituloSerie" => "JAMA Cardiol&#46;"
                        "fecha" => "2022"
                        "volumen" => "7"
                        "paginaInicial" => "36"
                        "paginaFinal" => "44"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34705022"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lipoprotein&#40;a&#41; in atherosclerotic cardiovascular disease and aortic stenosis&#58; a European Atherosclerosis Society consensus statement"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Kronenberg"
                            1 => "S&#46; Mora"
                            2 => "E&#46;S&#46;G&#46; Stroes"
                            3 => "B&#46;A&#46; Ference"
                            4 => "B&#46;J&#46; Arsenault"
                            5 => "L&#46; Berglund"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehac361"
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                        "tituloSerie" => "Eur Heart J&#46;"
                        "fecha" => "2022"
                        "volumen" => "43"
                        "paginaInicial" => "3925"
                        "paginaFinal" => "3946"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36036785"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Frequent questions and responses on the 2022 lipoprotein&#40;a&#41; consensus statement of the European Atherosclerosis Society"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "S&#46; Mora"
                            2 => "E&#46;S&#46;G&#46; Stroes"
                            3 => "B&#46;A&#46; Ference"
                            4 => "B&#46;J&#46; Arsenault"
                            5 => "L&#46; Berglund"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.atherosclerosis.2023.04.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Atherosclerosis&#46;"
                        "fecha" => "2023"
                        "volumen" => "374"
                        "paginaInicial" => "107"
                        "paginaFinal" => "120"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37188555"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "It is now time to focus on risk before age 40"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Gidding SS&#44; Robinson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2019.04.064"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2019"
                        "volumen" => "74"
                        "paginaInicial" => "342"
                        "paginaFinal" => "345"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31319916"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polygenic scores to assess atherosclerotic cardiovascular disease risk&#58; clinical perspectives and basic implications"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46;G&#46; Aragam"
                            1 => "P&#46; Natarajan"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCRESAHA.120.315928"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circ Res&#46;"
                        "fecha" => "2020"
                        "volumen" => "126"
                        "paginaInicial" => "1159"
                        "paginaFinal" => "1177"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32324503"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevention of atherosclerosis from childhood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "O&#46; Raitakari"
                            1 => "K&#46; Pahkala"
                            2 => "C&#46;G&#46; Magnussen"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41569-021-00647-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Cardiol&#46;"
                        "fecha" => "2022"
                        "volumen" => "19"
                        "paginaInicial" => "543"
                        "paginaFinal" => "554"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34987194"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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