Managing Residual CVD Risk: The Role of HDL Cholesterol – Issue 3

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Issue Author
Philip Barter, MD
Director, The Heart
Research Institute
Professor of Medicine
University of Sydney
Sydney, Australia

Series Chair
Clinical Professor
University of Illinois
School of Medicine
Peoria, IL
Director of Preventive Cardiology
Sterling Rock Falls Clinic, Ltd.
Sterling, IL

Click Here to read Dr. Tóth’s commentary on this issue.



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Issue 3: Current and Emerging HDL-Targeted Therapies in Cholesterol Management


The well-documented inverse relationship between levels of high-density lipoprotein cholesterol (HDL-C) and cardiovascular risk1,2 has fueled the search for strategies designed to increase levels of HDL-C in high-risk people in whom the level is low. In support of numerous human population studies, there are many studies in animals showing that interventions that increase the HDL concentration inhibit the development of atherosclerosis.3-6 It must be emphasized, however, that there is still no direct evidence in humans that HDL-raising interventions translate into a reduction in clinical cardiovascular events. Nevertheless, until proven otherwise, it is reasonable to attempt to increase the HDL concentration in high-risk people in whom the level of HDL-C is low. The first (and possibly the most important) line of therapy designed to raise HDL-C levels is lifestyle modification.




Lifestyle Approaches to Increase Levels of HDL-C

Weight Reduction

One of the commonest causes of having low HDL-C is being overweight or obese.7 Successful and sustained weight reduction in such people is almost always accompanied by a modest increase in the concentration of HDL-C.7

Physical Activity

People whose level of aerobic activity is very high tend to have high concentrations of HDL-C. Furthermore, if an inactive, overweight person with a low level of HDL-C embarks on a sustained program of physical activity, there is generally an increase in the level of HDL-C that may be substantial in some people.8 Indeed, it may be argued that the single most important preventable cause of having a low level of HDL-C in the 21st century is being physically inactive. Any increase in physical activity is likely to be beneficial, although there is evidence that the increase in HDL-C is greater in those exercising for more that the currently recommended 30 minutes per day of moderate-intensity exercise.

Smoking Cessation

People who smoke tend to have lower levels of HDL-C than is found in age and gender matched non-smokers.9,10 Furthermore, stopping smoking may be accompanied by more than a 10% increase in the concentration of HDL-C.10,11 While it is unclear to what extent a low level of HDL-C contributes to the increased cardiovascular (CV) risk in smokers, it is reasonable to assume that it does add to risk and that an increase in the level of HDL-C associated with stopping smoking is worth achieving.


There is abundant evidence that alcohol consumption increases the level of HDL-C.12 To date, the mechanism is uncertain. Nor is it known whether the increase in HDL concentration associated with alcohol consumption is cardio-protective. Because of other potential medical and social problems associated with alcohol consumption, alcohol should not be recommended as a therapy to increase the level of HDL-C.


Implementation of Therapeutic Lifestyle Changes

The beneficial effects of lifestyle change as a strategy to raise the level of HDL-C are well established. Indeed, the circumstantial evidence is compelling that cardiovascular risk will be significantly reduced if an overweight person loses weight, if an inactive person becomes active, and if a smoker quits smoking. There is also a generally held view in most populations that it is desirable to be a lean, active non-smoker. Despite this, the numbers of overweight and obese are increasing worldwide, the level of physical activity is decreasing rather than increasing, and a disturbing number of people are still smoking.

So, while we are succeeding in promoting the message that being lean, active, and non-smoking reduces the risk of developing cardiovascular disease (CVD), we are failing dismally in our efforts to persuade people that they need to take control of their lives and to act on what they know. So, communication is not enough; strategies must be found that result in educational messages being translated into action. In the meantime, it is necessary to consider using HDL-raising medications in high-risk people whose level of HDL-C is low. The problem is that there are currently no HDL-C raising agents with anything like the efficacy of statins to lower the level of low-density lipoprotein cholesterol (LDL-C). And there is still no direct evidence that drug-induced increases in the level of HDL-C translate into a reduction in CV risk.



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