Lp(a) Does Predict Risk in Blacks, New ARIC Data Show

December 01, 2011

December 1, 2011 (Houston, Texas) — Elevated levels of lipoprotein (a) [Lp(a)] are associated with cardiovascular events in African Americans, and the risk is comparable to that seen in whites, a new analysis of the Atherosclerosis Risk in Communities (ARIC) study shows [1].

These findings are particularly important because previous research has failed to find any association between Lp(a) levels and CVD risk in blacks, say Dr Salim S Virani (Methodist DeBakey Heart and Vascular Center, Houston, TX) and colleagues in their paper, published online November 29, 2011 in Circulation.

But this is likely because prior work was underpowered to look at this issue, and the new results now indicate that elevated Lp(a) levels should be considered a risk factor for CVD in African Americans, senior author Dr Christie Ballantyne (Baylor College of Medicine, Houston, TX) told heartwire .

In an accompanying editorial [2], Dr Paul Ridker (Brigham and Women's Hospital, Boston, MA) says the new findings fill a clinical gap and "provide closure for one longstanding debate in the Lp(a) field. We can remove the paradox for African Americans and take pathophysiologic comfort from the fact that almost all populations with elevated Lp(a) indeed have elevated risk."

But what is still needed for Lp(a) is evidence, preferably from randomized trials, that those at high risk due to elevated levels would benefit from a specific therapy, says Ridker, noting that several lipid-lowering agents in development significantly reduce Lp(a), including mipomersen, cholesteryl ester transfer protein (CETP) inhibitors, and niacin. "Unfortunately, little such data currently exist," he notes.

But Ballantyne, for his part, says he often measures Lp(a) levels in situations "where there is a bad family history," because there is evidence that levels of Lp(a) are hereditary, and they can be elevated in individuals even when LDL-cholesterol levels are relatively normal. In such people, "I would say, let's be more aggressive with lifestyle management and smoking cessation, and I would consider using a statin and aspirin," he notes.

Largest Prospective Study Evaluating Lp(a) and Events in Blacks

In the new prospective ARIC evaluation, plasma Lp(a) was measured in 3467 African Americans and 9851 whites who were followed for 20 years. There were 676 CVD events in blacks and 1821 events in whites over this time period.

As has been previously observed, Lp(a) levels were almost three times higher in blacks than in whites. But in apparent contradiction to almost all earlier work, increasing quintiles of Lp(a) were just as predictive of future CVD events in the African Americans as in whites.

Adjusted hazard ratios per race-specific, 1-standard-deviation-greater log-transformed Lp(a) were 1.13 for incident CVD, 1.11 for incident CHD, and 1.21 for ischemic strokes in blacks. For whites, the respective HRs were 1.09, 1.10, and 1.07. Quintile analysis showed that risk for incident CVD was graded but statistically significant only for the highest compared with the lowest quintile of Lp(a) [HR 1.35 for African Americans, HR 1.27 for whites].

Ballantyne says that most prior studies "had been severely underpowered for events in African Americans," whereas the new analysis is the largest to date evaluating the associations between Lp(a) and CVD events in blacks, "so we had some power. And we see there is increased risk for both CHD events and stroke for [increasing levels of Lp(a)] in African Americans. It makes a lot of biological sense."

Ridker agrees, stating that the "embedded piece of preventive cardiology wisdom" that decreed that Lp(a) was not predictive of risk in blacks may prove to be "a faux clinical pearl" that entered the literature simply due to poor statistical power of prior studies.

And Ballantyne observed, "When we have insufficient power, we have to be careful that we don't make major conclusions."

Reminder as to Why Population Studies of Ethnic Minorities Still Matter

One possible explanation for prior findings, however, could be that many of these smaller studies assessed only coronary heart disease as the outcome, say the Texas researchers.

"The higher risk estimates for ischemic strokes than for incident CHD events in our study suggest that elevated Lp(a) in African Americans might confer higher risk for a cerebrovascular event than for a coronary vascular event," they observe.

Ridker says this serves as a reminder "as to why population studies of underrepresented minorities continue to matter."

Virani reports research support from Merck and the National Football League Charities (all grants to the institution and not individual), Ballantyne reports grant/research support from Abbott, AstraZeneca, Bristol-Myers Squibb, diaDexus, GlaxoSmithKline, Kowa, Merck, Novartis, Roche, Sanofi-Synthelabo, Takeda, the National Institutes of Health, American Diabetes Association, and American Heart Association (all paid to the institution, not individual). Disclosures for the coauthors are listed in the paper. Ridker reports no conflicts of interest.

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