Elevated Lp(a) Can Increase Cardiovascular Risk in People with High Blood Pressure

Rishi Rikhi, MD, MS

An analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) study is providing new insight into interactions of lipoprotein(a) (Lp[a]) and hypertension with cardiovascular risk in primary prevention populations.

The latest example of the growing recognition of Lp(a)’s role in cardiovascular risk, results of the study suggest the presence of elevated Lp(a) was associated with an additional increase in risk of cardiovascular disease vents among patients with hypertension, but no increased risk was observed for those with elevated Lp(a) and no hypertension relative to those without elevated Lp(a) and no hypertension.

“High blood pressure is a known cardiovascular disease risk factor, and lipoprotein(a) is a type of inherited ‘bad’ cholesterol that may also lead to cardiovascular disease,” said lead investigator Rishi Rikhi, MD, MS, a cardiovascular medicine fellow at Atrium Health Wake Forest Baptist Medical Center, in a statement. “We found that among people with hypertension who have never experienced a stroke or heart attack before, lipoprotein(a) seems to increase the risk of cardiovascular disease and risk of a major cardiovascular event like heart attack or stroke.”

With interest in further exploration of the role of Lp(a) in modifying cardiovascular risk, Rikhi and a team of colleagues designed the current study to assess the longitudinal relationship of Lp(a) and hypertension to cardiovascular outcomes within a primary prevention cohort derived from the MESA study. From the study, investigators obtained data for 6674 individuals for inclusion in their analyses. This cohort was 52.8% female, 38.6% White, 27.5% Black, 22.1% Hispanic, and 11.9% Chinese American. The cohort had a mean age of 62.1 (SD, 10.2) years and the mean follow-up was 13.9 (SD, 5.0 years).

For the purpose of analysis, the study population was stratified into 4 groups based on presence of elevated Lp(a) and hypertension. Those in group 1 had an Lp(a) less than 50 mg/dL and no hypertension, group 2 had an Lp(a) greater than or equal to 50 mg/dL and no hypertension, group 3 had an Lp(a) less than 50 mg/dL and hypertension, and group 4 had an Lp(a) greater than or equal to 50 mg/dL and hypertension.

Investigators planned to use Kaplan-Meier curves and multivariable Cox proportional hazard models were used to estimate associations of Lp(a) and hypertension with time to cardiovascular disease events. Investigators defined time to cardiovascular disease events as a centrally adjudicated myocardial infarction, resuscitated cardiac arrest, nonfatal stroke, fatal stroke, and coronary heart disease death. Of note, nonfatal stroke did not include transient ischemic attack.

Upon analysis, results indicated there was no increase in risk for cardiovascular disease events for those with elevated Lp(a) and no hypertension relative to their counterparts without elevated Lp(a) and no hypertension in fully adjusted models (HR, 1.09 [95% CI, 0.79-1.50]). In contrast, when compared to those without elevated Lp(a) and no hypertension, results indicated those a statistically significant increase in cardiovascular event risk was observed among those without elevated Lp(a) and with hypertension (HR, 1.66 [95% CI, 1.39-1.98]) as well as those with elevated Lp(a) and with hypertension (HR, 2.07 [95% CI, 1.63-2.62]). Further analysis suggested those with elevated Lp(a) and with hypertension had an increased risk of cardiovascular disease events (HR, 1.24 [95% CI, 1.01-.153]) relative to their counterparts with hypertension but without elevated Lp(a).

“We found that the overwhelming amount of cardiovascular risk in this diverse population appears to be due to hypertension,” Rikhi said. “Additionally, individuals with hypertension had even higher cardiovascular risk when lipoprotein(a) was elevated. The fact that lipoprotein(a) appears to modify the relationship between hypertension and cardiovascular disease is interesting, and suggests important interactions or relationships for hypertension, lipoprotein(a) and cardiovascular disease, and more research is needed.”

This study, “Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA,” was published in Hypertension.