Women are usually about ten years older than men when they have their first heart attack or stroke because they are protected by estrogen. Identifying those at increased risk earlier in life and initiating preventive treatment before a cardiac event could be an important way to improve cardiovascular outcomes in women. Researchers think they have found just such an early-warning indicator.

Levels of high-sensitivity C-reactive protein, low-density lipoprotein cholesterol (LDL cholesterol, the so-called bad cholesterol) and lipoprotein(a) can accurately predict a person's risk of cardiovascular disease over a 5 to 10 year follow-up period. Researchers from Harvard wanted to see if these biomarkers could accurately predict the risk of a first cardiovascular event in women over a much longer period of time.

“It doesn't make any sense to start a statin in your late 60s and early 70s when we could have predicted your risk for high cholesterol in your 30s and 40s.”

If women were routinely screened for these three biomarkers using widely available inexpensive tests, preventive treatment could be started much earlier, Paul Ridker, lead author on the study, told TheDoctor. “Physicians can't treat what they don't measure,” he explained.

Medications such as low-dose colchicine and statins are available to lower levels of high-sensitivity C-reactive protein and LDL cholesterol, and some younger women would probably benefit from taking them, Ridker added. As he put it, “It doesn't make any sense to start a statin in your late 60s and early 70s when we could have predicted your risk for high cholesterol in your 30s and 40s.”

The researchers measured baseline levels of high-sensitivity C-reactive protein, a biomarker of inflammation, LDL cholesterol and lipoprotein(a) in the blood of almost 28,000 female healthcare providers enrolled in the Women's Health Study. Their average age at study enrollment was about 55 years old, and they were followed for 30 years. During the follow-up period, more than 3,660 participants experienced a first cardiovascular event, a combined measure of heart attack or stroke, surgery to restore circulation or death from cardiovascular-related causes.

Participants were grouped into five categories, from the highest to lowest levels of these three biomarkers. Women with the highest levels of high-sensitivity C-reactive protein had a 70 percent greater risk of a first cardiovascular event compared to women with the lowest levels. Those with the highest LDL cholesterol levels had a 36 percent greater risk than those with the lowest cholesterol levels. Women with the highest levels of lipoprotein(a) had a 33 percent greater risk than those with the lowest levels.

“We know Black and Latinx populations have elevated levels of these markers that go unscreened and silent.”

A limitation of the current study is that minority women only represent about five percent of participants in the Women's Health Study, yet these markers are as effective in predicting cardiovascular risk in minority populations as they are in white populations. In fact, measuring levels of these markers might be more effective in reducing cardiovascular risk in minority populations than many other preventive measures, suggested Ridker, the Eugene Braunwald Professor of Medicine at Harvard Medical School. “We know Black and Latinx populations have elevated levels of these markers that go unscreened and silent.”

There are already data showing that these three markers accurately predict the risk of cardiovascular events in men. Long-term follow-up data on men are needed, however, the researchers said, in order to generalize the findings of the current study to both women and men.

Ridker, director of the center for cardiovascular disease prevention at Brigham and Women's Hospital, said his team hopes to continue the Women's Health Study for at least another ten years.

The study and related editorial were published in the New England Journal of Medicine (NEJM).