Cardiovascular Disease — 3

Figure 5.2. Prevalence of coronary atherosclerosis seen at young ages, with different thresholds of lesion size. Adapted from EM Tuzcu et al., “High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: Evidence from intravascular ultrasound,” Circulation 103, no. 22 (June 2001): 2705–10, https://doi.org/10.1161/01.cir.103.22.2705.

An important prospective study in Denmark used CT (computed tomography) coronary angiograms to assess more than ninety-five hundred people aged forty years or older without symptoms or known heart disease and followed them for three and a half years. About half of the participants had no evidence of atherosclerosis. The rest fit into one of the categories in figure 5.3. Obstructive or extensive coronary artery disease was associated with an eight- to ninefold increased risk of heart attack; when both were present, the risk increased to thirteenfold, compared with those without atherosclerosis. The results for heightened risk of death or heart attack were similar. Even nonobstructive but extensive atherosclerosis carried a threefold risk of a heart attack. These findings emphasize the high frequency of coronary artery disease in people without any symptoms. Even with short duration of follow-up, nonobstructive disease carries significant risk. That’s why screening is so important. Wouldn’t it be great to know who is at high risk without doing CT coronary angiograms indiscriminately for the population?

The American Heart Association calls healthy diet, physical activity, avoidance of nicotine, healthy sleep, healthy weight, and healthy levels of lipids, blood glucose, and blood pressure “Life’s Essential 8.” These factors are key drivers of atherosclerosis, but genetics also plays a role. While not common, that’s why some people who are perfectly healthy, with no hypertension, diabetes, or lipid disorder, can go on to have heart attacks or require procedures to restore normal blood supply. About one in twenty people with coronary atherosclerotic disease present before age forty to forty-five, known as premature CAD, and up to 60 percent without any history in their family. As discussed in chapter 1, polygenic risk scores can help determine a person’s risk of heart disease. They are being implemented in some health systems in the United States, such as Mass General Brigham, and in some life insurance companies. They are also increasingly becoming available through several commercial entities including 23andMe, Genetype, Genomic PLC, Open DNA, Ambry Genetics, Myriad Genetics, and Haplotype Labs. For the individuals from Mass General Brigham who scored in the top 10 percent, classified as high risk, there was about a twofold risk of developing heart disease across ancestries, up to nearly a fourfold increase among people of Asian ancestry. In a large NIH-supported project that defined high risk for coronary disease as scoring in the top 5 percent, that twofold risk across ancestries was independently replicated. In twenty-five hundred people assessed for ten different disease polygenic risk scores, coronary heart disease was the one that detected high risk most commonly. A prospective study of more than ninety-six thousand participants in China highlighted the importance of the polygenic risk score for predicting cardiovascular diseases, along with lifestyle, and their additive impact.