Kidney and hypertension in older adults | Medicina Clínica (English Edition)

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Demographics</span><p id="par0005" class="elsevierStylePara elsevierViewall">Ageing is associated with different degrees of chronic kidney disease &#40;CKD&#41;&#44; although 11&#37; of older patients diagnosed with CKD do not have any underlying nephropathy&#44; suggesting that ageing itself may condition a progressive deterioration of kidney function<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; The prevalence of CKD in Spain in those over the age of 65 is above 20&#37;&#44; and approximately 38&#37; of adults over 70 have an estimated glomerular filtration rate &#40;GFR&#41; of less than 60&#160;ml&#47;min&#47;1&#46;73&#160;m<span class="elsevierStyleSup">2</span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; It is estimated that almost half of people over the age of 75 meet the criteria set by the <span class="elsevierStyleItalic">Kidney Disease Improving Global Outcome</span> &#40;KDIGO&#41; guidelines for a diagnosis of CKD<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; The incidence of dialysis initiation has also been shown to increase with age&#46; According to the <span class="elsevierStyleItalic">US Data System</span>&#44; the median age of patients starting dialysis is 65&#160;years&#44; but the fastest growing group is found in those over 75<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; The <span class="elsevierStyleItalic">Kidney Disease Outcomes Quality Initiative</span> &#40;KDOQI&#41; guidelines establish a classification of CKD based on the degree of GFR and&#47;or presence of kidney damage signs and consider the different stages of CKD to be valid for people of all ages<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; However&#44; there is much debate as to what is the normal range of renal function in the elderly&#44; and whether decreased GFR is due to a physiological ageing process or whether it is due to intrinsic renal disease&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Anatomical and functional changes of the ageing process</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Renal structural changes</span><p id="par0010" class="elsevierStylePara elsevierViewall">The main renal structural changes associated with ageing are quite nonspecific and not always easy to distinguish from the changes produced by other processes&#44; such as arterial hypertension &#40;HTN&#41; or diabetes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Perhaps the most characteristic features are the progressive decrease in renal volume&#44; estimated to be around 10&#37; per decade from the fourth decade of life onwards&#44; the decrease in the number of intact glomeruli&#44; which in turn appear hypertrophic&#44; glomerular sclerosis and interstitial fibrosis<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; The earliest descriptions of nephron mass reduction with ageing are quite old and come from autopsy studies&#46; Recently&#44; Denic et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> showed that the number of intact glomeruli decreases from approximately one million in the second decade of life to 600&#44;000 in the eighth decade&#44; with an increase in histologically detectable sclerosed glomeruli of up to 10&#37; and a statistically significant negative relationship between the number of glomeruli and their volume<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Renal functional changes</span><p id="par0015" class="elsevierStylePara elsevierViewall">The GFR decreases with age&#44; but several studies question whether there is an unambiguous relationship between age and the decrease in GFR&#46; The <span class="elsevierStyleItalic">Baltimore Longitudinal Study on Ageing</span>&#44; in a group of 254 people with a 24&#160;year follow-up&#44; without HTN or other causes of CKD showed that the mean decrease in GFR was 0&#46;75&#160;ml&#47;min&#47;year&#44; a third of the individuals had their GFR completely stable&#44; and even a small group showed a small increase in GFR<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; Other longitudinal studies have confirmed similar results&#44; estimating that the reduction in GFR with age can range from 0&#46;4&#160;ml&#47;min to 3&#46;8&#160;ml&#47;min per year<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a>&#46; This variability lies in the different rate of nephron loss in different individuals&#44; but also in the adaptive capacity of intact glomeruli&#46; In fact&#44; the glomeruli of aged kidneys behave like hyperfiltrating glomeruli&#44; with a dissociation between anatomical changes and loss of function &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Ageing is characterised by progressive tubular dysfunction&#46; Basically&#44; the elderly patient usually maintains a sodium balance similar to that of young patients&#59; however&#44; in situations of volume depletion the response to the reduction in sodium excretion is significantly slower&#46; This phenomenon contributes to the susceptibility of the elderly to the development of acute renal failure &#40;ARF&#41;&#46; Potassium excretion is decreased by a reduction in the transtubular potassium gradient&#44; the presence of a certain degree of hyporeninaemic hypoaldosteronism and a decrease in the sodium load reaching the distal nephron in situations of volume depletion&#46; This somewhat explains the predisposition to drug-induced hyperkalaemia in elderly patients<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; The urine concentration and dilution mechanism is also altered&#44; explaining the high incidence of nocturia&#44; the predisposition to dehydration and hypernatremia in cases of low intake&#44; and hyponatremia when excess fluids are administered<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">With age&#44; renal renin production decreases&#44; contributing to a reduction in plasma renin activity and&#44; therefore&#44; angiotensin II and aldosterone synthesis&#44; with their respective impact on electrolyte homeostasis and blood volume<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46; The generation of natriuretic substances such as PGE<span class="elsevierStyleInf">2</span> and dopamine is reduced&#44; increasing sensitivity to salt<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46; Plasma levels of 1&#44;25-dihydroxyvitamin D are generally in the low-normal range&#44; indicating a decrease in renal hydroxylation of vitamin D<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; Serum erythropoietin increases with age&#44; due to a complex mechanism that is not entirely well defined<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46; Finally&#44; renal formation of klotho&#44; a cofactor of FGF23 to which systemic actions are attributed&#44; decreases with age&#44; which may contribute to ageing in other parts of the body<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Mechanisms involved in kidney ageing</span><p id="par0030" class="elsevierStylePara elsevierViewall">Transcriptome analysis of aged kidneys has identified overexpression of genes related to extracellular matrix synthesis and inflammation<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; These two factors play a key role in the development of renal structural and functional alterations with ageing&#44; but they are only the final common pathway of a process that is actively being studied &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The molecular basis of the renal ageing phenomenon includes cellular senescence&#44; which includes genomic instability&#44; loss of telomeres and DNA repeats at the end of chromosomes as a result of loss of telomerase activity&#44; chronic oxidative damage contributing to telomeric shortening resulting in the senescent phenotype&#44; a certain genetic programming favouring accelerated cellular ageing&#44; with subsequent inflammatory phenotype&#44; thus inducing changes in the kidney<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> and finally cell death&#46; This cell damage is essentially determined by chronic inflammation and cellular senescence&#46; The accumulation of non-dividing senescent cells can compromise the tissue&#39;s capacity for renewal and repair&#46; In addition&#44; certain genes that are overexpressed by the senescent response may encode for soluble proteins &#40;cytokines&#44; adhesion molecules and growth factors&#41; that can alter the tissue microenvironment&#44; thereby altering its structure and function<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#8211;24</span></a>&#46; Along with this&#44; environmental and hormonal factors can also influence genetic determinants&#44; affecting renal behaviour in old age &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Clinical implications</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Glomerular filtration rate measurement in clinical practice</span><p id="par0035" class="elsevierStylePara elsevierViewall">In clinical practice&#44; the quantification of renal function often uses formulae developed to estimate GFR from serum creatinine and physical and laboratory parameters&#44; all of which have a certain degree of inaccuracy and are not validated in individuals over 70&#160;years of age&#46; The most accurate and the one most used today is the <span class="elsevierStyleItalic">Chronic Kidney Disease Epidemiology Collaboration</span> &#40;CKD-EPI&#41;&#44; created in 2009<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Clinical guidelines define CKD as the presence for at least 3&#160;months of a GFR of less than 60&#160;ml&#47;min&#47;1&#46;73&#160;m<span class="elsevierStyleSup">2</span> or evidence of structural or functional renal abnormalities other than GFR<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a>&#46; It is these abnormalities that should be evaluated in the elderly and&#44; in their absence&#44; moderate reductions in GFR should not be considered pathological&#44; although they should be considered when administering drugs&#46; In summary&#44; we could conclude that individuals over the age of 75 with a GFR above 45&#160;ml&#47;min&#47;1&#46;73&#160;m<span class="elsevierStyleSup">2</span> and without other renal abnormalities should not be considered nephrological patients&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Clinical problems associated with kidney dysfunction</span><p id="par0045" class="elsevierStylePara elsevierViewall">The reduction in renal haemodynamic and functional reserve that occurs with ageing may compromise the organ&#39;s adaptation to acute ischaemia or following exposure to nephrotoxic drugs&#44; increasing susceptibility to ARF&#46; The existence of previous CKD has been described as the greatest risk factor for developing ARF&#46; Thus&#44; the risk doubles for GFR between 45-59&#160;ml&#47;min compared to GFR &#62;&#160;60&#160;ml&#47;min<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46; Proteinuria also seems to double the risk of ARF regardless of GFR<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46; Other factors&#44; such as the higher prevalence of certain comorbidities in the elderly&#44; polypharmacy&#44; and the fact that certain procedures &#40;contrasts&#44; surgical interventions&#41; are performed more often in this population group&#44; may also contribute to increasing the incidence of ARF<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46; It should be underlined that age over 65 is a risk factor for progression to CKD after an episode of ARF&#46; A meta-analysis reveals that 31&#37; of patients &#62;65 did not recover their previous kidney function after an episode of ARF compared to 26&#37; in younger patients<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">As in younger people&#44; the presence of CKD in the elderly can be associated with a number of complications&#46; In general&#44; the clinical manifestations of CKD develop progressively&#44; with great variability from patient to patient&#44; depending on the rate of progression and the amount of functioning renal mass&#46; A GFR of less than 30&#160;ml&#47;min usually signals the borderline at which CKD becomes symptomatic&#44; after which a wide range of clinical manifestations develop in parallel with the progressive stage&#44; including water and sodium metabolism disorders&#44; which can lead to heart failure &#40;HF&#41;&#44; HTN&#44; oedema and hyponatraemia&#59; electrolyte disturbances&#44; with hyperkalaemia being the most relevant&#44; bone-mineral metabolism disturbances with the occurrence of hypocalcaemia and hyperphosphatemia&#44; responsible for the pruritus typical of CKD&#46; Metabolic acidosis&#44; normocytic normochromic anaemia&#44; altered lipid profile with elevated triglycerides and LDL cholesterol may also occur together with low HDL cholesterol levels&#44; glucose intolerance&#44; hyperuricemia&#44; and increased bleeding time due to platelet dysfunction&#44; thus increasing the risk of bleeding in these patients<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a>&#46; Intervention on these complications of CKD should be individualised according to functional status&#44; accompanying symptoms and disease progression&#46; The ideal treatment should be aimed at improving the patient&#39;s quality of life rather than addressing isolated laboratory figures&#46; Adequate control of cardiovascular risk factors&#44; anaemia&#44; acidosis&#44; and malnutrition are key to achieving this effect&#46; It should be noted that&#44; in the elderly patient&#44; the clinical symptoms of CKD are often absent and that in many cases the casual finding of elevated urea and creatinine levels points to the diagnosis&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The factors for progression of CKD in the elderly patient are the classic ones described for the general population plus hyperfiltration&#46; It is therefore recommended to correct modifiable risk factors and to intervene on the glomerular overload caused by the reduction in renal mass&#46; In this sense&#44; adequate control of blood pressure levels&#44; also modifying intrarenal hemodynamics by blocking angiotensin&#44; is essential to prevent the potential reduction in GFR&#46; Proteinuria is a clinical marker that must be considered&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Medication dose adjustment to glomerular filtration rate</span><p id="par0060" class="elsevierStylePara elsevierViewall">One of the greatest consequences of ageing is the increased susceptibility to drug toxicity&#46; Decreasing renal excretory capacity and&#44; to a lesser extent&#44; changes in hepatic metabolism and changes in body composition that occur with age&#44; contribute to changes in the pharmacokinetics of many drugs<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&#46; The same is true for the pharmacodynamics of many drugs&#58; age regulates the sensitivity and physiological response to their actions&#46; When polypharmacy and polypathology are added to this&#44; the medication dose adjustment becomes a complex problem&#46; It is recommended to adjust the dose to the estimated renal function&#44; whether it is a patient with a diagnosis of CKD or a decrease in GFR associated with ageing&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Renal hypertension in the elderly</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Demographics</span><p id="par0065" class="elsevierStylePara elsevierViewall">HTN is one of the most prevalent diseases in the world today&#46; Its global prevalence in developed countries is around 25&#37;&#44; while in the elderly it can be 60&#8211;80&#37;&#46; With an estimated 4&#46;4&#37; of the world&#39;s population being over 80&#160; years of age by 2050&#44; the global prevalence of HTN will increase steadily over the next few years<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">During the ageing process&#44; various structural and functional changes and modifications occur in the cardiovascular system that favour an increase in systolic blood pressure &#40;SBP&#41;&#46; This increase is evidenced in 65&#37; of patients over the age of 60 and in 90&#37; of those over 70&#44; with a higher incidence in women&#46; Systolic HTN is associated with a significant increase in cardiovascular risk<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#46; Diastolic blood pressure &#40;DBP&#41;&#44; however&#44; undergoes a reverse process&#44; starting to decline from the age of 50 in both sexes&#44; with a consequent increase in pulse pressure &#40;PP&#41;&#46; PP is defined as the difference between SBP and DBP and is a powerful predictor for the development of cardiovascular events<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Anatomical and functional changes of the ageing process</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Arterial wall modifications</span><p id="par0075" class="elsevierStylePara elsevierViewall">The changes associated with ageing that favour an increase in blood pressure &#40;BP&#41; generally have to do with the changes our body undergoes with age&#46; Environmental factors linked to the lifestyle habits of each individual&#44; such as salt intake&#44; smoking and overweight&#44; as well as genetic factors&#44; also play a role&#46; The most characteristic and significant structural change that occurs with ageing is a loss of elasticity and distensibility of the great arteries&#44; with an increase in their stiffness and a decrease in their capacitance&#44; which determines an impairment to buffer the pressure generated from the left ventricle&#44; thus leading to a progressive increase in SBP&#46; When these same changes take place in the arteries of medium and small calibre&#44; what occurs is an increase in peripheral resistance&#44; increasing DBP<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Structural changes in the arterial wall are involved in the etiopathogenesis of these processes&#44; especially in its intima and media layers&#46; The arterial media layer is made up of smooth muscle cells surrounded by extracellular matrix&#44; which in turn is made up of collagen and elastin&#46; With age&#44; the endothelium becomes more permeable to the passage of macromolecules and the deposits of calcium&#44; phospholipids and cholesterol esters increase&#46; The elastic fibres of the internal elastic lamina lose their elasticity and their degradation is accelerated by an increase in the activity of elastases&#46; There is an expansion of the extracellular matrix by deposition of collagen&#44; elastin and proteoglycans and hypertrophy and hyperplasia of smooth muscle cells<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Endothelial dysfunction</span><p id="par0085" class="elsevierStylePara elsevierViewall">Arterial stiffness is not only a consequence of structural changes in the vascular wall&#44; but also depends on changes in the synthesis of vasoactive endothelial mediators&#46; During ageing&#44; endothelium-dependent vascular functions are altered&#44; a phenomenon called endothelial dysfunction&#44; which is characterised by an imbalance between the synthesis and release of vasodilator and vasoconstrictor substances&#44; especially affecting the nitric oxide &#40;NO&#41;-dependent vasodilator response and favouring vasoconstriction and increased peripheral vascular resistances<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;37</span></a>&#46; In turn&#44; NO deficiency negatively influences leukocyte adhesion&#44; platelet aggregation and smooth muscle cell proliferation&#44; thus contributing to the development of atherosclerosis&#46; In addition&#44; the endothelial secretion of certain substances&#44; such as interleukins&#44; endothelin&#44; or <span class="elsevierStyleItalic">insulin growth factor</span> 1&#44; would also favour the formation of collagen matrix in the arterial wall<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#46; Data from experimental and clinical studies link elevated levels of asymmetric dimethylarginine &#40;ADMA&#41;&#44; together with reduced NO bioavailability&#44; to the endothelial dysfunction observed in HTN in the elderly<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Changes in neurohormonal regulatory mechanisms</span><p id="par0090" class="elsevierStylePara elsevierViewall">An increase in angiotensin II&#44; angiotensin converting enzyme and mineralocorticoid receptor levels is observed in ageing&#46; Elevated levels of these factors stimulate extracellular matrix production and result in the development of inflammation&#44; oxidative stress&#44; and fibrosis&#44; thus contributing to the arterial stiffness seen with age&#46; Evidence from recent years points to the renin&#47;prorenin receptor and its profibrosing role as another angiotensin II independent pathway to increase extracellular matrix<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The role of the sympathetic nervous system in the maintenance of hypertension in humans is well known&#46; Circulating catecholamine levels increase with age&#44; more in women than in men&#44; generally after the age of 40&#46; However&#44; beta-adrenergic vasodilation of vascular smooth muscle decreases with ageing due to a decrease in both the number and affinity of beta receptors&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In the autonomic nervous system&#44; age-related reduction in baroreceptor function contributes to the high prevalence of orthostatic hypotension&#46; It has also been shown that arterial stiffness alters the homeostatic mechanism responsible for maintaining the stability of BP and tissue perfusion during different physiological conditions&#44; such as orthostatism&#44; exercise&#44; postpartum or stress&#44; thus conditioning a great variability of SBP in these situations <a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical implications</span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Cardiovascular complications</span><p id="par0105" class="elsevierStylePara elsevierViewall">In the elderly&#44; isolated systolic HTN is the most prevalent form of HTN&#46; There are numerous studies that relate it to an increase in cardiovascular morbidity and mortality&#46; The Framingham study&#44; with a follow-up of more than 30&#160;years&#44; found that patients with isolated systolic HTN had an increased risk of death from cardiovascular disease of 1&#46;8 in males and 4&#46;7 in females<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46; Another epidemiological study&#44; the <span class="elsevierStyleItalic">Multiple Risk Factor Intervention Trial</span> &#40;MRFIT&#41;&#44; with a follow-up of more than 300&#44;000 individuals over 10&#160;years&#44; also evidenced a significant increase in cardiovascular mortality linked to SBP values<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a>&#46; Other studies&#44; on the other hand&#44; suggest that BP has a limited predictive value for total mortality after the age of 70&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The prevalence of coronary heart disease is higher in hypertensive than in normotensive elderly&#44; although this difference becomes less pronounced with every decade of increase&#46; Left ventricular hypertrophy &#40;LVH&#41; and cardiac diastolic dysfunction are quite common in these patients&#44; and it is possible that this difficulty in cardiac filling is primarily responsible for the low cardiac output and the development of HF<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&#46; Atrial fibrillation clearly increases its incidence in hypertensive elderly patients and has been associated with an increased risk of cardiovascular events&#44; stroke&#44; and impaired kidney function&#46; HTN&#44; age&#44; and proteinuria have a negative impact on the course of CKD&#44; which in turn is associated with increased cardiovascular risk&#46; SBP is an independent marker of worsening kidney function in the elderly with isolated systolic HTN&#46; Regarding the risk of cerebrovascular disease &#40;CVD&#41;&#44; the association of HTN and ischemic or hemorrhagic CVD increases with age&#44; with isolated systolic HTN being an important risk factor&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Impact on neurocognitive functions</span><p id="par0115" class="elsevierStylePara elsevierViewall">Numerous observational studies have documented the association between elevated BP levels in middle-aged people and the risk of vascular dementia and Alzheimer&#39;s disease&#46; This relationship was first observed in the Framingham study&#44; in which elevated BP levels detected in the previous 20&#160;years had an inverse correlation with cognitive status in untreated hypertensive patients<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46; Since this initial observation&#44; there have been numerous epidemiological studies that have verified this association between hypertension and cognitive impairment<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a>&#46; Others&#44; however&#44; have not demonstrated this association&#44; observing discrepancies between the results of various studies&#46; The same occurs with the results of the studies that analysed the decrease in the incidence of dementia with antihypertensive treatment&#46; While the Syst-Eur and PROGRESS studies showed a decrease in the incidence of dementia in the treatment group<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">46&#44;47</span></a>&#44; in the SCOPE&#44; SHEP and HYVET studies these differences were not significant<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">48&#8211;50</span></a>&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Treatment</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Therapeutic targets</span><p id="par0120" class="elsevierStylePara elsevierViewall">Until relatively recently&#44; it was not clear whether or not to treat hypertension in the elderly&#46; Currently&#44; there is sufficient evidence on the benefit of hypertension management in the elderly population&#44; at least in terms of cardiovascular morbidity and mortality since there does not seem to be a clear impact on cognitive functions&#46; A Cochrane review of 12 clinical trials showed that adequate management of hypertension in people over 60&#160;years of age was associated with a reduction in mortality&#46; Another review of 5 clinical trials by MacMahon and Rodgers<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> on antihypertensive treatment and reduction of cardiovascular morbidity and mortality in the elderly demonstrated a reduction in stroke incidence of 34&#37;&#44; in coronary events of 19&#37; and in overall cardiovascular mortality of 23&#37;&#46; These results were observed with a reduction of 12&#8722;14&#160;mmHg in SBP and 5&#8722;6&#160;mmHg in DBP&#44; with a follow-up period of 5&#160;years&#46; Other intervention studies carried out in the elderly population have also shown the benefit of treating both HTN and isolated systolic HTN<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">46&#8211;49</span></a>&#46; Thus&#44; octogenarians in the HYVET study showed a 30&#37; reduction in the rate of stroke&#44; a 64&#37; decrease in HF episodes and a 21&#37; decrease in the occurrence of major cardiovascular events and all-cause mortality<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">It is difficult to find consensus on BP target in the different guidelines for the management of HTN in the elderly&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> tries to summarize the opinions of the different scientific societies<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">52&#8211;56</span></a>&#46; In general&#44; there is a tendency to recommend increasingly intensive BP monitoring&#46; However&#44; the therapeutic target must be individualized according to the clinical characteristics of each patient and the individual tolerance to the decrease in BP levels&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Therapeutic strategies</span><p id="par0130" class="elsevierStylePara elsevierViewall">As in any patient with essential HTN&#44; lifestyle modifications are the first step to consider in the treatment of hypertensive older people&#46; The measures are the same as those suggested in other populations&#44; and the TONE study has confirmed their usefulness<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a>&#46; Perhaps special attention should be paid to weight loss&#44; as potential loss of muscle mass is not advisable in older people&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Drug therapy must be started after failure of lifestyle modification measures and must be individualized&#44; choosing the drug that best controls BP and with the fewest side effects&#46; It is important to bear in mind a number of clinical aspects specific to this group of patients&#44; such as age-related physiological changes&#44; the presence of comorbidities&#44; common polypharmacy&#44; and cognitive function&#46; In this sense&#44; the studies that have analysed aspects of quality of life have ruled out any negative impact with antihypertensive treatment in this population&#44; although some drugs may have a negative impact&#44; such as beta-blockers&#44; which in the TONE study were associated with major depressive symptoms&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In view of the experience accumulated in the various published clinical trials&#44; most international guidelines propose the same antihypertensive drugs that are used in young patients and that include the main therapeutic groups&#58; thiazide diuretics&#44; calcium channel blockers&#44; angiotensin converting enzyme inhibitors &#40;ACEI&#41;&#44; angiotensin II receptor blockers &#40;ARBs&#41; and beta-blockers&#46; The American guidelines do not specifically recommend any drug in the antihypertensive treatment of patients over 60<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a>&#46; The British <span class="elsevierStyleItalic">National Institute for Health Care Excellence</span> &#40;NICE&#41; guidelines do not include beta-blockers as the first line of treatment in older patients<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a>&#46; European guidelines favour the use of calcium channel blockers or thiazide diuretics in the absence of comorbidities that determine the use of other antihypertensives<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a>&#46; Recently&#44; based on the results of different studies&#44; it has been proposed that patients over 80 years of age should be prescribed ACEI or ARBs among the first-line drugs<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">52&#8211;57</span></a>&#46; The use of alpha blockers as first-line therapeutic agents is not generally recommended&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">A significant percentage of older patients develop mainly systolic hypertension&#44; with a significant increase in PP&#44; responding inadequately to the above therapies and presenting extemporaneous elevations of their SBP&#44; often related to emotional or physical stress&#44; leading to recurrent emergency interventions&#46; It should be remembered the stiffness of the large central thoracic arteries is critical in the genesis of the condition in these patients&#44; and that the elasticity of these arteries cannot be restored&#46; In these patients&#44; consideration should be given to the appropriate use of drugs to reduce cardiac output&#44; which&#44; together with the capacitance of the great arteries&#44; is responsible for SBP&#46; Drugs such as diuretics or beta-blockers may be useful in treating these patients but should be used with caution because of possible side effects&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">It is worth noting that a new approach to the management of HTN is becoming increasingly relevant&#44; with a focus on making nocturnal blood pressure a validated therapeutic target&#46; Different studies have confirmed that nocturnal blood pressure is the best indicator of cardiovascular and cerebrovascular risk and that reducing it increases survival &#40;MAPEC&#44; <span class="elsevierStyleItalic">The Hygia Chronotherapy Trial</span>&#44; <span class="elsevierStyleItalic">HOPE</span>&#44; <span class="elsevierStyleItalic">The Syst&#46;Eur trial</span>&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a>&#46; The study by Hermida et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> provides robust evidence on the safety and efficacy of the nocturnal strategy of antihypertensive treatment and reinforces the importance of adequate blood pressure control on long-term prognosis&#44; with promising results on cardiovascular benefits that translate into a reduction of cardiovascular and cerebrovascular risk by 50&#8211;60&#37;&#44; with this benefit being maintained in renal patients&#46; The study also endorses ambulatory blood pressure monitoring &#40;ABPM&#41; as the best tool for the diagnosis of hypertension and for predicting the risk of heart attack and stroke and justifies its routine use in the clinic&#46;</p></span></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">The project has been financed with funds from the <span class="elsevierStyleGrantSponsor" id="gs0005">Carlos III Health Institute</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0005">PI17&#47;01513</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs0005">RD16&#47;0009&#47;0018</span>&#41; and of the <span class="elsevierStyleGrantSponsor" id="gs0010">Community of Madrid</span> &#40;NOVELREN-CM&#47;CLINIREN&#41;&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interests</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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              "titulo" => "Anatomical and functional changes of the ageing process"
              "secciones" => array:3 [
                0 => array:2 [
                  "identificador" => "sec0065"
                  "titulo" => "Arterial wall modifications"
                ]
                1 => array:2 [
                  "identificador" => "sec0070"
                  "titulo" => "Endothelial dysfunction"
                ]
                2 => array:2 [
                  "identificador" => "sec0075"
                  "titulo" => "Changes in neurohormonal regulatory mechanisms"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "sec0080"
              "titulo" => "Clinical implications"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0085"
                  "titulo" => "Cardiovascular complications"
                ]
                1 => array:2 [
                  "identificador" => "sec0090"
                  "titulo" => "Impact on neurocognitive functions"
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "sec0095"
              "titulo" => "Treatment"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0100"
                  "titulo" => "Therapeutic targets"
                ]
                1 => array:2 [
                  "identificador" => "sec0105"
                  "titulo" => "Therapeutic strategies"
                ]
              ]
            ]
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        ]
        8 => array:2 [
          "identificador" => "sec0110"
          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0115"
          "titulo" => "Conflict of interests"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-11-11"
    "fechaAceptado" => "2021-02-04"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1461898"
          "palabras" => array:5 [
            0 => "Aging"
            1 => "Kidney"
            2 => "Hypertension"
            3 => "Cardiovascular risk"
            4 => "CKD"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1461899"
          "palabras" => array:5 [
            0 => "Envejecimiento"
            1 => "Ri&#241;&#243;n"
            2 => "HTA"
            3 => "Riesgo cardiovascular"
            4 => "ERC"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Individuals over 65 years are the fastest expanding population throughout the world&#44; due to the increase in human life expectancy&#46; This growing geriatric population&#44; with increasingly associated chronic diseases&#44; has relevant medical&#44; social&#44; and economic impact&#46; Aging is characterized by progressive structural and functional changes in the kidney and in the cardiovascular system&#44; leading to decline in renal function and hypertension&#46; The purpose of this review is to describe the aging-related renal changes and blood pressure regulation during the aging process and their impact with regards to morbidity and mortality in these patients&#46; And to summarize the most appropriate therapeutic approaches in these situations based on the particularities of this population group&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Con el incremento de la esperanza de vida de la poblaci&#243;n&#44; las personas mayores de 65 a&#241;os son un grupo cada vez m&#225;s prevalente&#44; con el consiguiente aumento de patolog&#237;as cr&#243;nicas asociadas&#44; desencadenando un escenario de gran impacto sociosanitario&#46; Durante el proceso de envejecimiento&#44; se producen cambios tanto estructurales como funcionales en el ri&#241;&#243;n y en el sistema cardiovascular&#44; que condicionan la aparici&#243;n de alteraciones de la funci&#243;n renal e HTA&#44; problemas de salud de primer orden en la actualidad&#46; El objetivo de esta revisi&#243;n es describir los cambios en la funci&#243;n renal y en la regulaci&#243;n de la presi&#243;n arterial con el envejecimiento&#44; su impacto cl&#237;nico&#44; en especial en la morbimortalidad de los individuos&#44; y los enfoques terap&#233;uticos ante estas alteraciones&#44; orientados a las caracter&#237;sticas particulares de este grupo poblacional&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Bouarich H&#44; Ch&#225;vez Guill&#233;n A&#44; Rodr&#237;guez Puyol D&#46; Ri&#241;&#243;n e hipertensi&#243;n en el anciano&#46; Med Clin &#40;Barc&#41;&#46; 2021&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.medcli.2021.02.008">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;medcli&#46;2021&#46;02&#46;008</span></p>"
      ]
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Mechanisms of kidney ageing&#46; An integrated view&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Microscopic changes</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Glomerular</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Expansion of the mesangial matrix&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glomerular basement membrane thickening&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Glomerular atrophy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Increased volume of intact glomeruli&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Pericapsular fibrosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Podocytopathy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glomerulosclerosis &#40;focal and global&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tubulointerstitial</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Interstitial fibrosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tubular atrophy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Occurrence of diverticula precursors of simple cysts &#40;distal convoluted tubule and collecting tubule&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Vascular</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Arteriosclerosis of the great renal vessels&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Intimal fibrosis and hyperplasia of the interlobar arteries&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Communication between the afferent and efferent arterioles in the juxtaglomerular apparatus&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Macroscopic changes</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Decreased renal volume&#44; 10&#8722;30&#37; between the ages of 40&#8722;80 &#40;at the expense of the cortical volume&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Weight loss&#44; 10&#37; per decade</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Height decrease&#44; 0&#46;5&#160;cm per decade&#44; from the age of 40</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Focal cortical scars</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ERPF reduction&#44; 10&#37; per decade&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Decreased GFR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Impaired ability to store and excrete sodium&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Decreased potassium excretion&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Changes in the mechanism of urine concentration and dilution&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Increased vasoconstriction and decreased vasodilator reserve in the renal vascular bed&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Decreased renal renin production and generation of natriuretic substances&nbsp;\t\t\t\t\t\t\n
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                  \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">Decreased renal hydroxylation of vitamin D&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Increased serum erythropoietin levels&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Decreased renal production of klotho&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2013 ESH&#47;ESC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">SBP &#60;150&#160;mmHg&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#62;65&#160;yrs of age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2017 CJC&#47;CCS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">SBP &#60;120&#160;mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#62;75&#160;yrs of age&nbsp;\t\t\t\t\t\t\n
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                  \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">2017 ACC&#47;AHA&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">BP &#60;130&#47;80&#160;mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#62;65&#160;yrs of age&#44; not institutionalizedIndividualize in institutionalized patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2017 AAFP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#62;65&#160;yrs of age &#40;according to individual tolerance&#41;&nbsp;\t\t\t\t\t\t\n
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