Higher Subclinical Atherosclerosis in Black Americans Remains Unexplained

Even after adjusting for traditional cardiovascular risk factors as well as lifestyle and socioeconomic status, a new analysis made up mostly of women reveals a greater prevalence of early subclinical atherosclerosis in young non-Hispanic Black adults than in their Hispanic peers.

The cross-sectional study drew on data from the FAMILIA study, conducted in a lower-income neighborhood in Harlem, New York, and made up primarily of people of African-American and Hispanic descent. The cohort allowed researchers to zero in distinctions between these two groups, the authors note, disentangling social determinants of health from other potential risk factors.

Prior work has shown that higher levels of hypertension, obesity, and smoking in Black adults are drivers of the higher levels of cardiovascular disease in this group, senior author Valentin Fuster, MD, PhD (Icahn School of Medicine at Mount Sinai, New York, NY), told TCTMD.

“But the surprise is that once we actually completely adjust for that, there is something else,” he said. “There is something that we don't know that we have to explore further: new risk factors that we don't understand, genetic risk factors that we don't understand, maybe socioeconomic risk factors that were not tabulated and we don't understand, emotional stress, etc. . . . For the first time, we are saying that there is something else in the Black population that really leads to this number one killer. And the question is: what is it?”

FAMILIA Analysis

For their study, published in the July 19, 2022, issue of the Journal of the American College of Cardiology, Fuster along with lead author Josep Iglesies-Grau, MD (Institut de Cardiologie de Montréal, Canada), and colleagues performed bilateral carotid and femoral 3-dimensional vascular ultrasound (3DVUS) imaging on 436 adults in the Harlem neighborhood of New York City (mean age 38 years; 82.3% women; 66.3% Hispanic; 33.7% non-Hispanic Black). All participants were parents and caregivers of children enrolled in the FAMILIA trial.

At baseline, Black participants were more likely than Hispanics to have hypertension (OR 3.54; 95% 2.14-5.87), be active smokers (OR 3.15; 95% CI 1.83-5.41), and have higher body mass index (BMI; mean between-group difference 1.45 kg/m²; 95% CI 0.17-2.74). Mean 10-year Framingham cardiovascular risk score was 4.0%, and there were no differences by racial/ethnic category. In fact, 89% of the study population were classified as low risk.

Overall, 3DVUS identified subclinical atherosclerosis in 8.7% of the study population, with a mean global plaque burden of 5.0 mm³. Rates of atherosclerosis were significantly higher for non-Hispanic Black (12.9%) than Hispanic individuals (6.6%) as were rates of multiterritorial disease (8.2% vs 3.8%; P = 0.026 for both). The burden of disease, including both carotid and femoral, was also higher for Black compared with Hispanic adults (mean 9.0 vs 2.9 mm³; P = 0.028).

There is something that we don't know that we have to explore further: new risk factors that we don't understand, genetic risk factors that we don't understand, maybe socioeconomic risk factors that were not tabulated and we don't understand. Valentin Fuster

After adjusting for 10-year Framingham CV risk score, BMI, fruit and vegetable consumption, physical activity, and employment status, Black participants still had a greater prevalence of subclinical atherosclerosis compared with Hispanics (adjusted OR 3.45; 95% CI 1.44-8.29). Specifically, there was a nearly six-times higher likelihood of finding carotid disease in Black individuals (adjusted OR 5.94; 95% CI 2.17-16.26).

The study adjusted for the seven traditional cardiovascular risk factors—obesity, hypertension, hypercholesterolemia, diabetes, smoking, lack of exercise, and poor diet—but Fuster noted that there are now as many as 16 accepted risk factors in total, identified by artificial intelligence (AI).

In fact, AI may hold the key to unlocking why non-Hispanic Black patients have such a higher prevalence of subclinical disease, according to Fuster. “We have to search why,” he said. “Up until now, we had to take care of the hypertension, obesity, and smoking in the Black population. What we are now saying is we have to research what else is going on here that is unknown. And this in itself is a very important issue.”

Fuster also spoke to the potential of 3DVUS in helping to identify more subclinical disease, both in the research stage and clinically, in the “next 2 to 3 years.” This imaging modality can “look at the whole arterial system of individuals, the large arteries, and we will quantify this in cubic millimeters of disease,” he said. “This has never been done before and . . . is fascinating.”

Clinical Implications

Commenting on the study for TCTMD, Richard Cooper, MD (Loyola University Medical Center and Stritch School of Medicine, Chicago, IL), said there are likely “too many factors” outside of the statistical model used in this study to pinpoint the cause of the higher prevalence of disease in the Black population. “I don't think these studies are ever going to be helpful,” he told TCTMD in an email. “We have a mountain of data that Blacks and poor people have more ‘pathology’ for virtually everything. And we know it is living conditions. I don't think epidemiology has anything more to contribute.”

However, he added, further studies on “low-level background exposures, specifically pollution” will be helpful because this risk factor has been clearly linked with diabetes, renal disease, and “likely” vascular disease. “Of course, we already know the overall impact of pollution, but these new findings do actually explain a little of the ‘outside the model’ effect in concrete terms. But the methods used here—ultrasound, serum measures, etc—are not going to be helpful,” said Cooper. “And the focus on genomics/metabolomics is entirely without value for chronic diseases like CVD.”

Still, in an accompanying editorial, Ramdas G. Pai, MD, and Vrinda Vyas, MBBS (both University of California Riverside School of Medicine), write that these findings have “important clinical implications” given that subclinical atherosclerosis is likely linked to future risk of stroke or coronary events.

But the cross-sectional design of the study does not enable the determination of any causal relationships, they argue. “Social determinants of health, diet, and pollution may have epigenetic effects on the phenome and may be heritable as well, making it important for these often-ignored factors to be studied in detail. It would have been instructive to characterize the study population better in terms of the nontraditional risk factors.”

Further, Pai and Vyas say the inclusion of genomic studies as well as analyses of statin use, plaque composition, and coronary-bed disease through calcium scoring could have provided a clearer picture of the problem. However, they say a big strength of the study was its high proportion of women.

The editorialists call for future “rigorous” epigenetic studies to better understand how these interactions affect the evolution of cardiovascular disease so that strategies targeting specific environmental risk factors could be developed. This is especially needed in certain racial and ethnic populations where it seems the Framingham Risk Score might not be as applicable, as shown in this study for Black adults, they say. “New data are emerging in favor of imaging-based classification of CVD risk and has been shown to improve patient adherence to and compliance with risk-modifying interventions.”