High Lp(a) & Heart Disease Risk in Healthy Women

A new study published in JAMA Cardiology delivers a stark warning: elevated levels of lipoprotein(a) – a genetically determined lipid – are significantly correlated with increased cardiovascular risk in women over a 30-year period, even in those initially considered healthy. This isn’t simply confirming a known risk factor; it’s a potential paradigm shift in how we approach preventative cardiology, particularly given the current lack of widespread screening for this biomarker.

For decades, the focus in cardiovascular risk assessment has centered on traditional factors like cholesterol (LDL, HDL), triglycerides, blood pressure, and lifestyle. However, lipoprotein(a) has remained somewhat in the shadows. This is largely due to the challenges in measuring it accurately and, until recently, a lack of clear understanding of its clinical significance. The genetic component is key – unlike other lipids that can be significantly modified by diet and exercise, lipoprotein(a) is stubbornly resistant to these interventions. This makes identifying high-risk individuals *before* they experience cardiovascular events all the more critical.

The study, leveraging data from the Women’s Health Study (a cohort initially established to study aspirin’s role in stroke prevention), analyzed data from nearly 28,000 women followed for almost three decades. The sheer length of the follow-up period is a major strength, allowing researchers to observe long-term cardiovascular outcomes in relation to lipoprotein(a) levels. The findings are particularly concerning given that the women included were initially healthy, highlighting that elevated lipoprotein(a) poses a risk even in the absence of other traditional risk factors.

The Forward Look

The implications of this research are substantial. While lifestyle interventions and existing pharmacological treatments have limited impact on lipoprotein(a) levels, the study underscores the urgent need for increased awareness and, crucially, screening. The question now isn’t *if* we should screen, but *how* and *when*. We can anticipate a growing debate regarding the optimal screening strategy – should it be universal, targeted at individuals with a strong family history of premature cardiovascular disease, or reserved for those with persistently elevated LDL cholesterol despite aggressive treatment?

More importantly, the pharmaceutical industry is actively pursuing novel therapies specifically designed to lower lipoprotein(a). Several promising approaches, including antisense oligonucleotides and siRNA therapies, are currently in clinical trials. Positive results from these trials could dramatically alter the landscape of cardiovascular prevention, offering a targeted intervention for individuals identified as high-risk through screening. Expect to see increased investment and accelerated development in this area, driven by the growing recognition of lipoprotein(a)’s pivotal role in cardiovascular disease. The current study provides a compelling argument for prioritizing research and development in this space, potentially unlocking a new era of preventative cardiology.

References

1. Nordestgaard AT, Chasman DI, Moorthy V, et al. Thirty-year risk of cardiovascular disease among healthy women according to clinical thresholds of lipoprotein(a). JAMA Cardiology. Published online January 7, 2026. doi:10.1001/jamacardio.2025.5043

2. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352(13):1293-1304. doi:10.1056/NEJMoa050613