Earlier biomarker measurement may better estimate long-term cardiac risk

Measuring cardiac biomarkers earlier in life can help improve estimates of long-term cardiac risk, according to two recent studies.

In the first study, levels of high-sensitivity C-reactive protein (CRP), low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) were measured at baseline in 27,939 initially healthy U.S. women from the Women's Health Study, who were then followed for 30 years. The primary end point was a first major adverse cardiovascular event, defined as a composite of myocardial infarction (MI), coronary revascularization, stroke, or death from cardiovascular causes. The results were published Aug. 31 by the New England Journal of Medicine.

The mean age of the study participants was 54.7 years at baseline, and 94.0% were White. During 30 years of follow-up, there were 3,662 first major cardiovascular events. Risks over 30 years increased by quintiles of baseline levels for all three measured variables. When the top quintiles were compared with the bottom quintiles, covariable-adjusted hazard ratios for the primary end point were 1.70 (95% CI, 1.52 to 1.90) for high-sensitivity CRP, 1.36 (95% CI, 1.23 to 1.52) for LDL cholesterol, and 1.33 (95% CI, 1.21 to 1.47) for lipoprotein(a). Each biomarker contributed to the overall risk, and the greatest spread for risk was seen in models incorporating all three biomarkers.

The authors noted that non-White women are underrepresented in the Women's Health Study and that repeated biomarker measurements were not obtained, among other limitations. They concluded that one combined measure of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels in initially healthy U.S. women predicted incident cardiovascular events over a 30-year period. “Beyond implications for diagnostics, wellness interventions, and the selection of targeted therapy, these data strongly support the need for efforts to extend strategies for the primary prevention of atherosclerotic events well beyond traditional 10-year estimates of risk,” they wrote.

An accompanying editorial said the study provides powerful evidence that LDL cholesterol, high-sensitivity CRP, and lipoprotein(a) are important measures for risk prediction. “A long-term view can enable earlier recognition of cardiovascular disease risk in women and proactive preventive efforts to mitigate risk,” the editorialists wrote. “The best way to avoid cardiovascular disease in the future is to reduce risk factors today, because tomorrow will soon be here.”

The second study examined whether a one-time measurement of non-high-density lipoprotein (HDL) cholesterol or LDL cholesterol could predict cumulative lipid exposure during early adulthood, defined as ages 18 to 40 years, and risk for atherosclerotic cardiovascular disease (ASCVD) after age 40 years.

Researchers evaluated participants in the CARDIA (Coronary Artery Risk Development in Young Adults) Study who did not have cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had had at least three measures of LDL cholesterol and non-HDL cholesterol before age 40 years. They assessed whether a one-time measurement of LDL cholesterol or non-HDL cholesterol between ages 18 and 30 years could predict quartile of cumulative lipid exposure from ages 18 to 40 years, as well as any associations between quartiles of cumulative lipid exposure from ages 18 to 40 years and ASCVD events, defined as fatal and nonfatal MI and stroke, after age 40 years. The results were published Sept. 2 by the Journal of the American College of Cardiology.

A total of 3,995 CARDIA participants met inclusion criteria and were included in the final analysis. A one-time measure of non-HDL cholesterol and LDL cholesterol was found to have excellent discrimination for predicting whether a participant would be in the top or bottom quartiles of cumulative exposure (area under the curve, 0.93 for the four models). Absolute values that predicted whether a participant would be in the top quartiles with the highest simultaneous sensitivity and specificity were over 135 mg/dL for non-HDL cholesterol and over 118 mg/dL for LDL cholesterol; corresponding values for predicting being in the bottom quartiles were below 107 mg/dL and below 96 mg/dL, respectively. Those who were in the top exposure quartiles for non-HDL cholesterol and LDL cholesterol had demographic-adjusted hazard ratios of 4.6 (95% CI, 2.84 to 7.29) and 4.0 (95% CI, 2.50 to 6.33) for ASCVD events after age 40 years, respectively, versus each bottom quartile.

The researchers concluded that single measures of non-HDL cholesterol and LDL cholesterol between ages 18 and 30 years appear highly predictive of cumulative exposure before age 40 years, which itself strongly predicts ASCVD events later in life. “The absolute values of [non-HDL cholesterol] and [LDL cholesterol] that best predict a high exposure to atherogenic lipids in early adult life are substantially lower than those derived from studies of middle-aged adults,” they wrote. “Our findings may help guide the clinical assessment of lipid-associated risk in adults <40 years of age.”

An accompanying editorial said the study emphasizes the importance of prioritizing early prevention strategies that could have long-term effects on young adults' health and well-being. “Future studies should focus on understanding and addressing the barriers to ideal cardiovascular health in young adults, identifying more effective strategies for lipid screening and lowering in this segment of the population, and reducing health inequity by targeting high-risk subgroups that are not currently prioritized, including those with a high burden of adverse social determinants of health,” the editorialists wrote. “Only by listening to young adults and developing interventions tailored to their unique needs can we better support them to achieve optimal lipid levels now and a lifetime of cardiovascular health in the future.”