The worldwide obesity epidemic is progressing hand in hand with an increasing incidence of metabolic disorders, such as diabetes, hypercholesterolemia, and atherogenic dyslipidaemia (AD). AD is a typical characteristic in obese patients with metabolic syndrome, insulin resistance and type 2 diabetes,1 and carries a significant cardiovascular risk.2,3 The AD lipid profile is determined by low HDL-cholesterol (HDL-C) levels, elevated triglycerides (TG), and the presence of small, dense LDL particles, a combination that is highly atherogenic. Given its nature, treating AD with statins is frequently insufficient to provide overall lipid profile control, and fails to eliminate the residual vascular risk attributable to the non-LDL components of this lipid abnormality.4

Numerous studies have shown that patients with AD benefit from medical treatment targeted at normalising HDL-C and TG,5–9 and this evidence has been integrated into recommendations published in clinical practice guidelines.10–12 However, while the understanding of the association between an elevated cardiovascular risk and low HDL-C or high TG levels is a complex matter, it is clear that this relationship impacts on both coronary and cerebrovascular disease.13,14

Appropriate diagnosis and therapeutic management of AD in the community would help to reduce the residual risk associated with this disease and affected patients would benefit. In this respect, primary care physicians play a very important role, since they can implement preventive measures in a large percentage of patients, more so than in the hospital setting or the specialised clinic.15

The main aim of this study was to determine to what extent published consensus guidelines for the diagnostic and therapeutic management of AD12 are used in the primary care setting, and to evaluate the approach of the participating physicians towards the detection, diagnosis, and treatment of AD.

The study participants comprised 991 PC physicians involved in the management of patients with AD. Table 1 shows the distribution of participating physicians in each autonomous community; representation was highest in Andalusia (16.7%), Valencia (13.3%) and Galicia (11.0%).

In this study, we analysed clinical approaches to 4 proposed clinical cases illustrating different situations, in order to determine the extent to which PC physicians selected from all autonomous communities in Spain understand and apply AD consensus recommendations.12 The questions were primarily drawn up to investigate the diagnostic and/or therapeutic approach in typical cases commonly seen in routine practice, and to analyse the different diagnostic and therapeutic strategies in each case.

It is widely agreed that the benefit provided by intensive reduction of LDL-C has led to the general acceptance of “LDL-C-centred” measures.16 However, many patients with target LDL-C levels continue to have a persistent cardiovascular risk or residual risk associated with the presence of AD, particularly patients with type 2 diabetes, abdominal obesity, and/or metabolic syndrome. Almost all the physicians who participated in this study were aware of the importance of performing a lipid profile for the comprehensive assessment of a patient who has suffered an ACS. The importance of low HDL-C as a source of cardiovascular risk is well established,17,18 yet a substantial number of physicians still do not include HDL-C levels when determining lipid profiles, despite the evidence of an inverse prognostic relationship between HDL-C and cardiovascular morbidity and mortality, irrespective of LDL-C concentrations.19 The role of triglycerides in coronary heart disease is also of key importance. A metaanalysis of 29 prospective studies revealed an odds ratio for coronary risk of 1.72 when individuals with triglycerides in the upper tertile (corresponding to >178mg/dl) were compared with those with levels in the lower tertile (<115mg/dl), after adjustment for other principal cardiovascular risk factors.20 Moreover, high non-fasting triglyceride levels can be a marker for cardiovascular risk.21

More recently, non-HDL cholesterol figures have gained importance as an indicator of cardiovascular risk, and on occasions are even thought to have more prognostic value than LDL-C.22 A metaanalysis of studies published between 1994 and 2008 showed that individuals who achieved target LDL-C but did not achieve target non-HDL-C levels had a 32% higher risk than those who achieved both objectives.23 This may be attributed to the fact that non-HDL-C concentrations reflect not only LDL-C, but also all atherogenic particles in plasma corresponding to lipoproteins that contain apolipoprotein B.24 The European Atherosclerosis Society has set non-HDL-C as a secondary target in the treatment of dyslipidaemia,11 calculated as target LDL-C plus 30mg/dl. This is a parameter that is easy to calculate (TC minus HDL-C) and does not involve any additional cost.

In high-risk patients, such as those with type 2 diabetes, excess weight, and high cholesterol and triglyceride levels (see study case 2), little concordance emerged on the definition of the therapeutic target after LDL-C has been controlled: only 66% of participants indicated that in women, triglyceride control is achieved at a level of less than 150mg/dl and HDL-C should be higher than 50mg/dl, in accordance with international recommendations.11,16 This highlights some lack of clarity regarding the treatment of complex cases that, in the absence of a history of cardiovascular disease, must be considered as candidates for primary prevention of atherothrombotic and cardiovascular episodes.25 The situation is different in patients who are already receiving prophylactic treatment (secondary prevention). Despite lipid-lowering treatment, the role of AD as a determinant element among factors contributing to residual cardiovascular risk26 is well known, as confirmed by almost 97% of the participants. Clinicians, then, must (and do, according to the results of this survey) give great importance to regular monitoring of lipid levels, treatment efficacy, and detection of possible adverse effects. However, the frequency of monitoring remains controversial, and, as has been stated, is often influenced more by administrative and financial concerns than by clinical considerations.27

One strategy found to be useful in the overall control of dyslipidaemia is to use combined lipid-lowering treatment, with the administration of a statin to lower cholesterol in association with a fibrate for AD.28–30 Fenofibrate was the option used by most of our participants (over 95%) in combination with statins, compared to the more minority choices of nicotinic acid or gemfibrozil. Indeed, clinical practice guidelines and the European Medicines Agency (EMA) recommend fenofibrate for the treatment of mixed hyperlipidemia together with a statin, when triglycerides and HDL-C are inadequately controlled. The safety of this combination has been demonstrated in several studies,31–33 and there is evidence that fenofibrate confers additional clinical benefit on renal function34,35 and carbohydrate metabolism.36

Some limitations to the interpretation of our results must be taken into account. As in any qualitative study, our results are exploratory and the conclusions cannot be generalised. As this was a survey, the results represent certain opinions or knowledge, rather than objective data. We do not know if the participating physicians had received specific training in AD or not, nor did we determine the proportion of patients similar to the proposed cases seen in their daily clinical practice. When an individual case presents, other factors such as adherence, drug interactions, and the psychosocial situation must be taken into account in the comprehensive assessment of the patient, and these aspects were not addressed in this study.

This study is a first attempt to evaluate the approach and knowledge of physicians treating AD in the PC setting, as an initial step towards detecting possible shortcomings in training and the application of expert consensus guidelines in AD. Although study participants showed good knowledge of the subject, the high prevalence of this disease requires an additional effort to optimise detection and treatment, with the implementation of appropriate lifestyle interventions and the prescription of the best treatment. Emphasis must be placed on the need to perform a complete lipid profile for an overall assessment of the patient's cardiovascular risk, and to treat the residual risk associated with high triglycerides and low HDL-C with the recommended combination of a statin and fenofibrate.

This study has been financed by Mylan.

The authors state that they have no conflict of interests. All authors contributed equally to the preparation of this article.