Key Points:
- While drug trials evaluate the short-term cardiovascular risk associated with elevated, blood biomarkers, little is known about the long term (20-30 year) risk conferred by these biomarkers, alone or in combination.
- This epidemiological study evaluated the association between baseline levels of hsCRP, LDL-C, and Lp(a) of ~28,000 initially healthy participants in the Women’s Health Study with incident cardiovascular events over 30 years of follow-up.
- Each of the measures were independently associated with an increased adjusted hazard of incident cardiovascular events, and each biomarker provided additive information. Women in the highest quintile of all three biomarkers had the highest risk.
- These data indicate that a single combined measure at one point in time can have predictive value beyond the traditional 10-year risk score. Since all three are potentially modifiable, these findings might have significant implications for how we prevent heart disease.
Atherosclerosis develops over decades before becoming clinically apparent. Early and accurate risk stratification using modifiable biomarkers can help us identify not just who to target, but also what to target with preventative interventions.On August 31st 2024, the principal results of the “Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women” was presented at ESC Congress 2024 with simultaneous publication in the New England Journal of Medicine. The purpose of this study w as to determine if a single mid-life baseline measure of high sensitivity C-reative protein (hsCRP), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) (Lp(a)) obtained in midlife could predict incident cardiovascular risk over a 30 year period, alone or in combination.
This analysis included 27,939 initially health participants in the Women’s Health Study who had each measure assessed at baseline, with a mean starting age of 54.7 years. The exposure was the quintile level of each biomarker, alone and in combination. The primary outcome was time to first major cardiovascular events (centrally adjusted myocardial infarction, revascularization, ischemic stroke, or cardiovascular death) over 30 years. Cause specific Cox proportional models were used to estimate 30 years hazard ratios, adjusted for age, smoking, diabetes, blood pressure, renal function, use of hormone replacement, and body mass index, accounting for competing risks of death.
Individually, elevated hsCRP had the highest risk for the composite endpoint (HR 1.70 [95% CI 1.52-1.90]), followed by LDL-C (HR 1.36 [1.23-1.52]) then Lp(a) (HR 1.33 [1.21-1.47]). Compared to having none of the three biomarkers in the top quintile, having all three biomarkers in the top quintile was associated with a significantly increased risk of coronary (HR 3.7 [95% CI 2.9-4.7]) and ischemic stroke (HR 1.7 [95% CI 1.1-2.5]) events. The biomarkers were each independently predictive as well as additive. There was a stepwise increase in the hazard for the primary outcomes with each additional elevated biomarker.
Dr. Paul Ridker from the Brigham and Women’s Hospital, Boston, MA, concluded: “A single combined measure of hsCRP, LDL-C and Lp(a) among initially health American women was predictive of incident cardiovascular events over a 30 year period. As each of these is modifiable, these data support efforts to extend strategies for primary prevention well beyond traditional 10-year estimates of risk. We need to focus on lifelong risk and lifelong interventions…We need to focus on prevention among younger women for whom CVD remains underdiagnosed and undertreated…The time has come for universal screening of 3 simple modifiable risk factors.”