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Lipids, lipid modifying agents and cardiovascular risk: a review of the evidence - REVIEW ARTICLE
  Lipids, lipid modifying agents and cardiovascular risk: a review ...
"Accepted Article"; doi: 10.1111/j.1365-2265.2008.03490.x.
Lipids, lipid modifying agents and cardiovascular risk: a review of the evidence ...
Clinical Endocrinology June 2009
David Preiss and Naveed Sattar
BHF Glasgow Cardiovascular Research Centre, University of Glasgow Correspondence: Dr David Preiss, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK. Tel.: +44 141 330 3076; Fax: +44 141 330 1689; E-mail:
It is well-established that serum total-cholesterol, LDL-cholesterol, low HDL-cholesterol and calculated indices such as total cholesterol : HDL-cholesterol ratio or less commonly used indices such as non-HDL cholesterol are strongly predictive of cardiovascular events. Serum triglycerides, by contrast, are only modestly associated with coronary heart disease (CHD) in multivariate analysis and incorporation of triglycerides into prediction algorithms is therefore unlikely to improve their prediction capability. Meta-analysis of studies including > 90 000 subjects has provided robust evidence that statins reduce important clinical end-points. These included a 12% fall in all-cause mortality, 19% fall in CHD mortality and 23% fall in CHD mortality or myocardial infarction. Furthermore there are high quality data showing additional benefit of intensive statin therapy over standard statin therapy for secondary prevention of cardiovascular disease. However, meta-analysis of 10 fibrate trials has shown inconsistent evidence of vascular benefit and non-cardiovascular mortality has been slightly but consistently elevated in most fibrate trials and in meta-analysis. The general use of fibrates for cardiovascular risk reduction can therefore not be supported at present. Other second line agents such as bile acid sequestrants, nicotinic acid and omega-3 fatty acid supplements have been evaluated in a few randomized controlled studies in which cardiovascular benefit has been found but clearly further data are required to properly establish their use in clinical practice. Ongoing studies such as ACCORD, IMPROVE-IT, ASCEND, ORIGIN and HPS2-THRIVE should assist in answering outstanding questions over the next 5 years.
At present clinicians have at their disposal a wide range of lipid-modifying agents. However, the quality of data supporting their use which includes trials with surrogate markers such as serum lipids, measures of atherosclerosis such as intima-media thickness and coronary angiographic findings, and clinical end-point data is variable. In this article we review the evidence which provides or erodes support for each major lipid fraction as a cardiovascular risk factor, examine the common respective treatment options for abnormalities in these fractions, discuss recent trial data of lipid modifying agents together with the best available evidence for pharmacological therapy and, based on this information, give an opinion on current best practice. For statins where cardiovascular end-point data are abundant we discuss only these trials and for medicines with less or no supportive data from end-point trials we discuss both surrogate marker trials and available cardiovascular end-point data. A summary of the best current data is provided in Table 1 together with a list of important outcome studies which are currently ongoing. The present report is directed at clinicians and related health care workers in a wide range of disciplines including but by no means limited to cardiologists, lipidologists, endocrinologists, diabetologists and primary care physicians. We appreciate that many other specialities also now consider cardiovascular risk in their patients and thus the present review has wider relevance.
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