A landmark study funded by the National Institutes of Health (NIH) has revealed that specific blood markers namely low-density lipoprotein (LDL) cholesterol, lipoprotein(a) [Lp(a)], and C-reactive protein (CRP) can be powerful predictors of a woman’s future risk for cardiovascular disease (CVD), potentially decades before symptoms emerge. These findings have been recently presented at the European Society of Cardiology Congress 2024 and published in the New England Journal of Medicine.
Although CVD has traditionally been seen as a condition that predominantly affects men, it is an equally serious concern for women, with recent statistics showing that the number of deaths from CVD is higher in women than in men. In 2019, cardiovascular disease accounted for 31.4% of all male deaths and a staggering 34.6% of all female deaths. Considering the urgency, the American Heart Association issued a ‘Call to Action’ in 2022, urging for more focused efforts to reduce the burden and risk of CVD in women.
The study analyzed data from the Women’s Health Study, which enrolled 27,939 female healthcare providers in the United States between 1992 and 1995, with an average age of 55. Throughout a 30-year follow-up period, 3,662 participants experienced a major cardiovascular event, such as a heart attack, stroke, surgery to restore circulation, or cardiovascular-related death. The study found that women with the highest levels of LDL cholesterol had a 36% increased risk of developing cardiovascular disease compared to those with the lowest levels. Those with elevated Lp(a) levels had a 33% increased risk, while women with the highest CRP levels faced a 70% increased risk. When all three markers were evaluated together, women with the highest levels had more than a 1.5-fold increased risk of stroke and a more than threefold increased risk of coronary heart disease compared to those with the lowest levels.
Although the study focused solely on women, researchers believe that similar findings would likely apply to men. Recent advances in understanding have shown that elevated inflammation levels can interact with lipids, exacerbating the risk of CVD . This interplay highlights the importance of maintaining lower levels of both inflammation and lipids to reduce cardiovascular risks.
The study also provides critical new insights into the biological mechanisms underlying CVD. Immune cells, which normally help repair the body after injury or infection, can become activated in response to excess cholesterol or plaque build-up in the arteries. This activation triggers inflammatory signals, leading to a hyper-inflammatory environment where plaque can grow, rupture, and eventually cause cardiovascular events such as heart attacks or strokes.
Based on these findings, the researchers emphasize the importance of primary prevention in maintaining optimal cardiovascular health. This involves adopting a heart-healthy lifestyle, including regular physical activity, a balanced diet, stress management, and avoiding tobacco. For individuals at increased risk, it may be necessary to take medications to lower cholesterol and reduce inflammation.
The study further underscores the importance of early intervention. It suggests that lifestyle changes and preventive measures taken earlier in life can accumulate over time, leading to significantly better cardiovascular outcomes later in life.
LDL cholesterol is commonly managed with statins, but screening for Lp(a) and CRP varies. Some countries recommend Lp(a) screening due to its genetic link, while in the United States, it is usually reserved for those with a personal or family history of heart disease. Treatment options exist for elevated Lp(a), with new therapies in development. CRP testing is also inconsistent and often depends on individual risk factors. In 2023, the FDA approved colchicine, an anti-inflammatory drug, to reduce cardiovascular risk in atherosclerosis patients, and further anti-inflammatory therapies are being explored.
This study represents a significant advancement in cardiovascular health, emphasizing the potential of blood markers to predict and prevent CVD. By focusing on these key markers, healthcare providers may be able to identify at-risk individuals earlier and implement strategies to prevent the onset of CVD, ultimately saving lives.
References
- Ridker PM, Moorthy MV, Cook NR, Rifai N, Lee IM, Buring JE. Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women. New England Journal of Medicine [Internet]. [cited 2024 Sep 2];0(0). Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2405182
- Tschiderer L, Seekircher L, Willeit P, Peters SAE. Assessment of Cardiovascular Risk in Women: Progress so Far and Progress to Come. Int J Womens Health. 2023 Feb 10;15:191–212.