Longer duration of both overall and abdominal obesity is strongly associated with subclinical coronary heart disease at midlife, as well as with increased progression of that disease over the course of 10 years, according to an analysis of the CARDIA study. The results were published in the July 17 issue of JAMA.
These associations are independent of the degree of adiposity, meaning that any level of overall or abdominal obesity corresponds with increased coronary risk, said Jared P. Reis, Ph.D., of the National Heart, Lung, and Blood Institute, Bethesda, Md., and his associates.
"Each additional year of overall or abdominal obesity beginning in early adulthood was associated with an HR or OR of 1.02 to 1.04 for coronary artery calcification and its progression" in middle age, they noted.
"Our findings suggest that preventing or at least delaying the onset of obesity in young adulthood may substantially reduce the risk of coronary atherosclerosis and limit its progression in later life," Dr. Reis and his colleagues said.
Dr. Jared Reis
The investigators examined this issue using data from the CARDIA (Coronary Artery Risk Development in Young Adults) study, a multicenter, community-based, longitudinal cohort assessing the development and the determinants of cardiovascular disease over time. The study comprised 5,115 young adults aged 18-30 years at baseline in 1985-1986 who resided in Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. These subjects now have been reexamined at 2, 5, 7, 10, 15, 20, and 25 years after baseline.
The presence and degree of coronary artery calcification was measured using chest CT at year 15 (2000-2001), year 20 (2005-2006), and/or year 25 (2010-2011).
For their study, Dr. Reis and his associates focused on 3,275 of these CARDIA participants who were not obese at baseline. Roughly 46% were black and 51% were women.
A total of 40.4% of their study subjects developed overall obesity and 41.0% developed abdominal obesity during follow-up, with significant overlap in these two categories. The mean age at onset of overall obesity was 35.4 years, and mean age at onset of abdominal obesity was 37.7 years. The mean duration of overall obesity was 13 years, and that of abdominal obesity was 12 years.
Subclinical coronary artery calcification was identified in 27.5% of the 3,275 study subjects overall.
A total of 38.2% of subjects who had overall obesity for more than 20 years were found to have coronary artery calcification, as were 39.3% of those who had abdominal obesity for more than 20 years. In contrast, these rates were 24.9% and 24.7% in nonobese adults, the investigators said (JAMA 2013;310:280-8 [doi:10.1001/jama.2013.7833]).
Similarly, 28.4% of subjects who had overall obesity for more than 20 years were found to have high scores on a measure of coronary artery calcification, as were 28.2% of those who had abdominal obesity for more than 20 years. In contrast, these rates were 15.2% and 15.5% in nonobese adults.
In addition, the rates of coronary artery calcification were higher with increasing duration of obesity. For example, the rate of calcification was 11 per 1,000 person-years in subjects with 0 years of obesity, compared with 16.7 per 1,000 person-years in subjects with more than 20 years of obesity.
Coronary artery calcification also was more likely to progress over the course of 10 years in obese than in nonobese subjects. Rates of progression were 25.2% in adults with more than 20 years of overall obesity and 27.7% in those with more than 20 years of abdominal obesity, compared with 20.2% and 19.5%, respectively, in nonobese adults.
The association between obesity and coronary artery calcification did not differ by subjects’ race or sex.
"These findings suggest that the longer duration of exposure to excess adiposity as a result of the obesity epidemic and an earlier age at onset will have important implications [for] the future burden of coronary atherosclerosis and potentially [for] the rates of clinical cardiovascular disease in the United States," Dr. Reis and his associates said.
They added that although the mechanisms by which prolonged adiposity affects coronary artery calcification are not precisely known, it is likely that the sustained expression and secretion of proinflammatory adipocytokines plays a role. "Extended impairment of the fibrinolytic system via increased markers of hypercoagulability and hypofibrinolysis may also contribute to atherosclerotic vascular disease," the researchers wrote.
Obesity is also thought to impair nitric-oxide-dependent endothelial function, increase oxidative stress, and upregulate vasoconstrictor proteins, all of which may contribute to coronary atherosclerosis, they said.
This study was supported by the National Heart, Lung, and Blood Institute. Dr. Reis reported no financial conflicts of interest; one of his associates reported receiving grants from Novo Nordisk.