Xanthelasma tied to a higher risk of heart attack and stroke

Patients with xanthelasma, the yellowish cholesterol deposits that can form on the eyelids, had about three times the rate of heart attack, stroke and transient ischemic attack (TIA, or mini-stroke) within a year of diagnosis compared with matched patients without the condition, according to a study published in April 2026 in Atherosclerosis.

Xanthelasma appears as soft, yellow plaques near the inner corners of the eyelids, caused by cholesterol-laden immune cells that build up under the skin. It shows up most often in women in their 50s and 60s. Dermatologists and ophthalmologists have long debated whether the condition is a cosmetic nuisance or a sign of deeper cardiovascular trouble.

As for cardiovascular disease, it remains the leading cause of death in the U.S., killing more than 900,000 people a year, according to the CDC. A marker that's easy to spot during a routine eye exam or dermatology visit could flag patients for closer cardiovascular monitoring years before a heart attack or stroke occurs.

This space has been examined in the past, but research on the link has produced mixed results. The authors of this study set out to test it in a larger, more rigorously matched population than earlier studies used.

Led by Negin Yavari, M.D., an ophthalmologist at the Byers Eye Institute at Stanford University School of Medicine, and her team, the study used TriNetX, a research network that pools deidentified electronic health records from more than 150 million patients across dozens of health systems in the U.S. and abroad.

Researchers identified patients diagnosed with xanthelasma with at least a year of follow-up, then built a comparison group of patients diagnosed with presbyopia, or age-related farsightedness, since both groups would have had a formal eye exam. Anyone with a prior heart attack, stroke or TIA was excluded from both groups. The cohorts were matched one-to-one on age, sex, race, ethnicity, cholesterol levels and cardiovascular risk factors such as hypertension and diabetes through propensity score matching, a technique that pairs patients with similar characteristics to reduce bias, leaving 17,770 patients in each group. Data were pulled from the network in November 2025. Researchers calculated hazard ratios, a measure of relative risk over time, using a Cox proportional hazards model, and tracked cumulative risk with a Kaplan-Meier analysis.

At one year, patients with xanthelasma had a heart attack rate of 1.00% compared to 0.35% for controls (hazard ratio 2.92). Stroke occurred in 0.95% of the xanthelasma group compared to 0.30% of controls (hazard ratio 3.35), and TIA occurred in 0.60% versus 0.19% (hazard ratio 3.29). This gap narrowed somewhat but persisted over time.

At five years, it was found that heart attack rates were 2.26% compared to 1.13% (hazard ratio 2.24), stroke 2.25% versus 1.03% (hazard ratio 2.46) and TIA 1.60% to 0.74% (hazard ratio 2.41). At 10 years, heart attack rates were 3.13% versus 1.73% (hazard ratio 2.14), stroke 3.00% compared to 1.53% (hazard ratio 2.32) and TIA 2.00% versus 1.13% (hazard ratio 2.10).

Every comparison was statistically significant. All-cause mortality, however, did not differ significantly between the two groups at any follow-up point. Patients with xanthelasma were also more likely to be prescribed cholesterol-lowering medication at every time point, though that gap, 22.76% versus 20.36% at one year, was modest next to the difference in cardiovascular events.

One secondary finding could matter most for payers and the care manager. For instance, when researchers compared xanthelasma patients with diagnosed dyslipidemia to those without it, rates of heart attack, stroke, TIA and death were similar between the two subgroups. Normal cholesterol on a lab panel didn't erase the added risk tied to the eyelid deposits. The authors pointed to prior research linking xanthelasma to certain apolipoprotein E gene variants, which are tied to atherosclerosis and stroke independent of measured cholesterol, as one possible explanation.

“Most of the patients with xanthelasma are seen by dermatologists for cosmetic reasons, while they may have undiagnosed or uncontrolled cardiovascular risk factors that contribute to this elevated risk,” the study authors wrote.

The study's size and length are notable strengths, including more than 35,500 matched patients from a racially and geographically diverse network, with outcomes tracked out to a decade and a control group chosen to avoid the bias of comparing eye-exam patients to the general population.

However, the authors warned that TriNetX relies on ICD-10 diagnosis codes, which carries some risk of misclassification, and the database doesn't record when patients started or stopped cholesterol-lowering therapy or at what dose. The researchers also lacked data on apolipoprotein B and lipoprotein(a) levels, increasingly used in cardiovascular risk assessment, and couldn't account for socioeconomic status, and patients who sought care outside the participating health systems wouldn't have been captured.

The authors concluded that xanthelasma should be treated as a clinical flag rather than dismissed as a cosmetic issue. Most patients see a dermatologist to have the deposits removed and may never be referred for a broader cardiovascular workup, even as risk factors go undiagnosed or uncontrolled.

They added that regular monitoring and management by primary care physicians could help put preventive measures in place, including lifestyle changes, cholesterol-lowering therapy and blood pressure control, for a group this study found faces meaningfully higher odds of a heart attack, stroke or TIA in the decade after diagnosis.