Elevated lipoprotein(a) plus high sensitivity CRP levels raise cardiac risk

Reuters Health - 09/09/2021 - Individuals with elevated lipoprotein(a) and high-sensitivity C-reactive protein (hsCRP) levels are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality, an observational study suggests.

"Lp(a) is not only an atherogenic and prothrombotic lipoprotein particle, it is also a proinflammatory one," Dr. Michael Shapiro of Wake Forest University Baptist Medical Center in Winston-Salem told Reuters Health by email. "Given that inflammation is an emerging target of therapy to potentially reduce residual atherosclerotic cardiovascular (ASCVD) risk, we were interested in examining the relationship between Lp(a), subclinical inflammation, and ASCVD in a population free of clinical ASCVD at baseline."

"We were not entirely surprised by the findings," he said. "A recent post-hoc analysis of the ACCELERATE trial (https://bit.ly/38Wh04i) reported that Lp(a) was associated with greater risk of major adverse cardiovascular events only when hsCRP was elevated (>2 mg/L). The findings of our study are consistent with this analysis and suggest that this relationship may be generalizable to both primary and secondary prevention."

As reported in the Journal of the American College of Cardiology, the current study included 4,679 participants from the Multi-Ethnic Study of Atherosclerosis Apolipoprotein ancillary data set. The mean age was 62; about half were women, depending on hsCRP levels; ethnicities were 38.3% white, 18% Chinese American; 24% African American; 19% Hispanic.

During a mean follow-up of 13.6 years, 684 CVD events occurred, and the analysis showed a significant interaction between Lp(a) and hsCRP. With hsCRP <2 mg/L, no significant CVD risk was observed at any level of Lp(a) from <50 mg/dL to >100 mg/dL.

However, with hsCRP at 2 mg/L or greater, a significant CVD risk was observed with Lp(a) of 50-99.9 mg/dL (hazard ratio, 1.36) and Lp(a) at 100 mg/dL or greater (HR: 2.09).

Elevations of either Lp(a) or hsCRP alone were not associated with increased CVD risk. In contrast, the combination of elevated Lp(a) (50 mg/dL or greater) and hsCRP (2 mg/L or greater) was independently associated with significant CVD risk (HR, 1.62) and all-cause mortality (HR: 1.39).

Dr. Shapiro said, "Measurement of subclinical inflammation with hsCRP may help to guide further clinical decisions related to Lp(a)-associated ASCVD risk, though this needs to be confirmed in trials designed to specifically answer this question. The ongoing HORIZON trial (https://bit.ly/2VzeP3y) is testing a specific Lp(a)-lowering drug in individuals with established ASCVD and elevated Lp(a), and should provide important insights into this relationship."

Dr. Wesley Milks, a cardiologist and assistant professor of clinical medicine at The Ohio State University Wexner Medical Center in Columbus commented in an email to Reuters Health, "This study has some potential to change practice in re-inspiring the ordering of hsCRP in appropriate cohorts."

"What is not clear to me from this study is whether elevated hsCRP represents a pre-existing/potentiating feature or rather the downstream effect of the elevated Lp(a) on atherogenesis," he said. "It is noteworthy that several traditional risk factors including obesity, hypertension, diabetes, and smoking were significantly more penetrant among the elevated h-CRP group; while the study purports to statistically control for this, I cannot help but wonder whether there remains an underlying confounder yet unaccounted for."

Further, he said, "the study would imply that if a patient has elevated Lp(a) yet normal hsCRP, he/she would not be at elevated ASCVD risk due to the Lp(a); I believe additional study is needed before suggesting such a conclusion to patients."

"Lp(a) has a highly skewed distribution in populations, and treating Lp(a) as a binary (i.e., greater or less than 50 mg/dl) is a considerable oversimplification," he added. "Many studies have focused on the particular risk elevation in the highest quintile (e.g., 80-99th percentile) of Lp(a), so analyzing a greater number of Lp(a) subgroups would be informative."

"My hypothesis would be that elevated hsCRP would not be requisite to observe elevated ASCVD risk among participants in the highest quintile of Lp(a)," Dr. Milks concluded.

SOURCE: https://bit.ly/2Vubh2t Journal of the American College of Cardiology, online September 6, 2021.

By Marilynn Larkin



Posted on 9 September 202115 September 2021