30-Year Study Links Key Biomarkers to Long-Term Cardiovascular Risk

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30-Year Study Links Key Biomarkers to Long-Term Cardiovascular Risk

30-Year Study Links Key Biomarkers to Long-Term Cardiovascular Risk

Long-Term Impact on Atherosclerosis for Up to 30 Years: NEJM Highlights Three Key Indicators for Predicting Cardiovascular Risk.

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. But how far back can the origins of these conditions be traced?

A recent large-scale, 30-year follow-up study, presented at the 2024 European Society of Cardiology (ESC) Congress and simultaneously published in The New England Journal of Medicine (NEJM), reveals that a single combined measurement of three indicators—high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) [Lp(a)]—can predict the risk of cardiovascular events for the next 30 years in healthy women.

An editorial in the same issue of NEJM emphasizes that the best way to prevent future cardiovascular disease is to start managing risk factors now.

30-Year Study Links Key Biomarkers to Long-Term Cardiovascular Risk

ESC Congress 2024: Focus on Personalized Cardiovascular Care

The theme of this year’s ESC Congress is “Personalizing Cardiovascular Care,” featuring the release of four clinical guidelines, 26 sessions on late-breaking science, and 12 Hot Line topic discussions. The conference covers 172 studies, and attendees can access these resources by scanning a QR code provided during the event.

Key Indicators: LDL-C, hs-CRP, and Lp(a)

Each of the three indicators studied carries significant weight. LDL-C, often referred to as “bad cholesterol,” is well-known, with substantial evidence linking elevated levels to adverse cardiovascular outcomes. Hs-CRP reflects low-grade vascular inflammation, and recent randomized controlled trials have shown that reducing inflammation can significantly lower the incidence of cardiovascular events. Lp(a), a lipid marker primarily determined by genetics, has gained increasing attention in recent years. Depending on the cut-off point used, approximately 20% to 33% of the global population has elevated Lp(a) levels.

Given that hs-CRP and Lp(a) are emerging therapeutic targets, and the development of atherosclerosis typically spans decades, previous evaluations of these markers have usually been limited to 5-10 years, with limited data on their long-term impact. This study fills a critical gap in the evidence.

Study Design and Findings

The study utilized data from the well-known Women’s Health Study (WHS), including 27,939 women who joined the study between 1992 and 1995. At the time of enrollment, their average age was 54.7 years, and they were in good health, providing blood samples for analysis. The women were followed until January 2023, with a maximum follow-up of 30 years and a median follow-up of 27.4 years (interquartile range: 22.6 to 28.5 years).

The primary endpoint was the first occurrence of major adverse cardiovascular events (MACE), including myocardial infarction, coronary revascularization, stroke, or cardiovascular death. During the follow-up, 3,662 cases of MACE were recorded.

Overall, higher levels of the three indicators independently predicted an increased risk of MACE over the next 30 years:

After adjusting for other potential confounders, women in the highest 20% for hs-CRP, LDL-C, and Lp(a) levels at baseline had a 70%, 36%, and 33% increased risk of MACE, respectively, compared to those in the lowest 20% for each indicator.
The risk associated with elevated Lp(a) levels was primarily seen in the highest 20%, with relatively smaller differences in risk among the remaining 80%.
Compared to the first 15 years, the impact of elevated hs-CRP and LDL-C levels only slightly decreased between 15 and 30 years, while the effect of elevated Lp(a) levels remained consistent over time. This suggests that these three indicators continue to influence MACE risk for up to 30 years.

The study also separately analyzed the impact of these three indicators on coronary heart disease events and stroke risk, with consistent findings.

Combined Risk of the Three Indicators

When considering the combined effect of the three indicators, the impact on MACE risk becomes even more pronounced. Compared to women with none of the three indicators in the highest 20%, those with one, two, or all three in the highest 20% had a 27%, 66%, and 163% increased risk of a first MACE event over the next 30 years, respectively. This trend remained similar when analyzing coronary heart disease and stroke risk separately.

Influence of Lipid-Lowering Treatment

The study also accounted for the potential impact of lipid-lowering treatments on MACE. At the start of the study, few participants were taking statins. Over time, nearly 60% required statin therapy. After adjusting for the timing of statin initiation, women in the highest 20% for hs-CRP, LDL-C, and Lp(a) levels at baseline still had a 65%, 62%, and 42% increased risk of MACE, respectively.

Overall, the study supports the notion that atherosclerosis begins early in life. The use of hs-CRP, LDL-C, and Lp(a) as indicators for the primary prevention of atherosclerosis has a lasting impact, extending up to 30 years, far beyond the previously validated 10-year period.

30-Year Study Links Key Biomarkers to Long-Term Cardiovascular Risk

[1] Paul M. Ridker, et al., (2024). Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women. The N Engl J Med, DOI: 10.1056/NEJMoa2405182

[2] Roger S. Blumenthal, Seth S. Martin. (2024). Prevention of Cardiovascular Disease — Don’t Stop Thinking about Tomorrow. The N Engl J Med, DOI: 10.1056/NEJMe2409080

[3] WHO Cardiovascular diseases (CVDs). Retrieved September 2, 2024

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Tags: Cardiovascular