AIM: Statins do not eliminate CV risk from low HDL levels

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Statins may lower bad cholesterol, but those with concomitant low levels of good cholesterol are still at an increased risk of cardiovascular events, according to a meta-analysis published Dec. 21 in the Annals of Internal Medicine.

Previous data from the Framingham Heart Study and Prospective Cardiovascular Munster Study found that a .026-mmol/L (1 mg/dL) decrease in high-density lipoprotein cholesterol (HDL-C) was linked to a 2 to 3 percent increase in risk for cardiovascular disease (CVD). More recently, a focus has been placed on lowering low-density lipoprotein cholesterol (LDL-C) levels to help reduce CVD. However, randomized controlled trials have shown that treating patients with statin therapy and lowering LDL-C levels may not prevent CVD risk.

To better understand the relationship between HDL-C levels and CVD risk, Haseeb Jafri, MD, of Tufts Medical Center and Tufts University School of Medicine in Boston, and colleagues performed a meta-analysis to evaluate whether or not statins can alter the relationship between HDL-C levels and MI.

The researchers identified 20 randomized controlled trials that included 543,210 person-years of follow-up. Within this population, 7,838 MIs, 12,220 CVD events, 3,088 coronary heart disease (CHD) deaths, 4,967 CVD deaths and 10,941 all-cause deaths occurred.

For those administered statins, the mean rates of outcomes of interest per 1,000 person-years of follow-up of the above were 11.5 for MIs, 23.7 for CVD events, 3.9 for CHD deaths, 7.8 for CVD deaths and 11.7 all-cause deaths, respectively.

The overall median decrease observed with statin therapy was an estimated four MIs and 4.1 CVD events per 1,000 person-years of follow-up.

Jafri and colleagues found that even after adjustment for on-treatment LDL-C levels, age, hypertension, diabetes and tobacco use, the results showed an inverse association between HDL-C levels and risk for MI in patients who were treated with statin therapy.

Every 0.26-mmol/L (10-mg/dL) decrease in HDL-C was linked to 7.1 and 8.3 more MIs per 1,000 person-years in statin-treated patients and control patients, respectively. The inverse association between HDL-C levels and MI did not differ between those treated with statins and the control patients.

The researchers said that limitations may stem from the associations not implying causality in the relationship between HDL-C levels and CV risk. The meta-analysis showed that the association between HDL-C levels and CV outcomes are not affected by statin therapy.

“Statin-treated patients are subject to the same magnitude of risk associated with lower levels of HDL-C as similar control participants,” the authors wrote.

Even after the researchers adjusted for the on-treatment LDL-C levels, age, hypertension and diabetes, the association between HDL-C levels with CV risk persisted, concluding that low HDL-C levels could at least be partially to blame for the CV risk in statin-treated patients.

“Even though the present findings support an association between low levels of HDL-C and increased cardiovascular risk in statin-treated patients, it should be acknowledged that HDL-C is not currently a target of national cholesterol guidelines; rather, levels of LDL-C and non-HDL-C are the specified primary and secondary targets for therapy,” the authors wrote. “Further, it is unclear whether interventions that increase HDL-C levels will further reduce CVD risk.

“The findings underscore the importance of recognizing the risk associated with low levels of HDL-C, even in statin-treated patients, and highlight the need for additional clinical investigation that targets levels of HDL-C in this context,” the authors concluded.