HDL-C: An important component of residual cardiovascular risk

A new meta-analysis by researchers at Tufts Medical Center, Boston, USA adds to evidence supporting low plasma levels of high-density lipoprotein cholesterol (HDL cholesterol) as an important contributor to residual cardiovascular risk in statin-treated patients. The data were reported during the American Heart Association Scientific Sessions, Orlando, USA, and are reviewed here by HDL Forum Editor Professor Philip Barter.

 

Jafri H, Alsheikh-Ali AA, Karas RH. Statin therapy does not reduce the increased cardiovascular risk associated with low levels of high-density lipoprotein cholesterol: evidence from randomized trials. Circulation 2009;120:S500 [Abstract 1423].

 

While lowering LDL cholesterol with a statin is clearly effective in reducing cardiovascular risk, supported by an extensive evidence-base (1), patients remain at unacceptably high residual risk (60-70%) of future cardiovascular events. This residual cardiovascular risk has been attributed to non-LDL lipid components against which statins have lower efficacy.

 

Population studies have clearly established that the plasma concentration of HDL cholesterol is a strong, independent, inverse predictor of cardiovascular heart disease, at least as important as LDL cholesterol (2-5). Analyses from clinical studies showed that a low baseline level of HDL cholesterol was predictive of major cardiovascular events during treatment with statins (6), even among patients who achieved LDL cholesterol levels < 70 mg/dL (1.8 mmol/L) (7).

 

In the current analysis, researchers identified 20 randomised controlled trials of statin therapy with a total of 543,210 person-years of follow-up. Over this period there were 7,838 heart attacks.

 

There was a significant relationship between the level of HDL cholesterol and risk for heart attack in both statin-treated (p=0.003) and non-statin treated patients (p=0.004) (Figure 1).

 

After adjustment for on-treatment LDL cholesterol and age, it was shown that every 10 mg/dL decrease in HDL cholesterol was associated with 7.6 (95% CI 3.9 to 11.3) and 7.8 (95% CI 2.8 to 13.0) more heart attacks per 1000 person-years in patients treated with statins or taking non-statin control therapy.  In contrast, statin treatment was shown to reduce the risk of heart attack by a median of 4.4 per 1,000 person-years.

 

Dr Richard Karas, Professor of Medicine, Tufts University School of Medicine and senior author of the study commented: ‘These new findings indicate that even if patients are on a statin and they have a low level of HDL cholesterol, they may need more than a statin to significantly reduce their risk of heart attack.’  These findings add to evidence that HDL cholesterol is an important component of residual cardiovascular risk.

 

References

1. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366:1267-78.

2. Assmann G, Schulte H, von Eckardstein A, Huang Y. High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis 1996;124 Suppl:S11-20.

3. Sharrett AR, Ballantyne CM, Coady SA, et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 2001; 104:1108-13.

4. Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 1989; 79:8-15

5. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High- density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977; 62:707-14

6. Sacks FM, Tonkin AM, Shepherd J, et al. Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project. Circulation 2000; 102:1893-900.

7. Barter PJ, Gotto AM, LaRosa JC et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007; 357: 1301-10.

 


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