肥胖病程长与冠状动脉钙化相关

《美国医学会杂志》7月17日发表的一项对CARDIA研究的分析显示，长时间的全身肥胖和腹部肥胖与中年亚临床冠心病及该病10年内进展增加强烈相关(JAMA 2013;310:280-8 [doi:10.1001/jama.2013.7833])。

上述关联独立于肥胖程度，意即任何水平的全身或腹部肥胖均提示冠状动脉风险增高。始于成年早期的全身或腹部肥胖的病程每增加1年，冠状动脉钙化及其进展的HR或OR为1.02~1.04。

Jared Reis博士

这项分析由美国国立心肺血液研究所的Jared P. Reis博士及其同事进行，采用的数据来自年轻成人冠状动脉风险发生(CARDIA)研究。CARDIA是一项评估心血管疾病随时间推移的发生和决定因素的多中心社区纵向队列研究，于1985年~1986年从阿拉巴马州伯明翰、芝加哥、明尼阿波利斯和加州奥克兰纳入5,115例基线年龄18~30岁的年轻成人，并在基线后2、5、7、10、15、20和25年对这些受试者再次检查。在第15年(2000~2001)、第20年(2005~2006)和/或第25年(2010~2011)采用胸部CT检测有无冠状动脉钙化及其程度。

Reis博士及其同事分析的对象是这些CARDIA受试者中基线时无肥胖的3275例受试者，约46%为黑人，51%为女性。共40.4%的受试者在随访期间发生全身肥胖，41.0%发生腹部肥胖，这两个类别的受试者显著重叠。全身肥胖的平均发生年龄为35.4岁，腹部肥胖的平均发生年龄为37.7岁。全身肥胖的平均病程为13年，腹部肥胖为12年。

在3,275例受试者中，亚临床冠状动脉钙化的检出率为27.5%。在全身肥胖病程20年以上的受试者中，冠状动脉钙化检出率为38.2%，在腹部肥胖病程20年以上的受试者中，检出率为39.3%。相比之下，在未曾发生全身肥胖和未曾发生腹部肥胖的成人中，检出率分别为24.9%和24.7%。

相似地，在全身肥胖病程20年以上的受试者中，冠状动脉钙化评分高的受试者比例为28.4%，在腹部肥胖病程20年以上的受试者中，该比例为28.2%。相比之下，在未曾发生全身肥胖和未曾发生腹部肥胖的成人中，该比例分别为15.2%和15.5%。

此外，肥胖病程越长，冠状动脉钙化发生率越高。例如，在肥胖病程0年的受试者中，钙化发生率为11/1,000人-年，而在肥胖病程20年以上的受试者中，钙化发生率为16.7/1,000人-年。

肥胖受试者10年内的冠状动脉钙化进展率也高于非肥胖受试者。在全身肥胖病程20年以上的受试者中，进展率为25.2%，在腹部肥胖病程20年以上的受试者中，进展率为27.7%，而在未曾发生全身肥胖和未曾发生腹部肥胖的成人中，进展率分别为20.2%和19.5%。

肥胖与冠状动脉钙化之间的关联不依受试者种族或性别而存在差异。

研究者表示，该分析结果表明，在成年早期预防或至少推迟肥胖的发生可显著降低冠状动脉粥样硬化风险并限制其后续的进展。虽然目前尚不十分清楚长时间肥胖影响冠状动脉钙化的机制，但这可能与促炎性脂肪细胞因子的持续表达和分泌有关。高凝和低纤溶标志物增高导致纤溶系统长时间受损可能也参与导致动脉粥样硬化血管疾病。此外，有学者认为肥胖可损害一氧化氮依赖性血管内皮功能、增加氧化应激及上调血管收缩蛋白，所有这些均可导致冠状动脉粥样硬化。

该分析获美国国立心肺血液研究所支持。Reis博士声明无经济利益冲突，一名研究者声明从诺和诺德公司获得资金。

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By: MARY ANN MOON, Cardiology News Digital Network

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.

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.