The Association of Overt and Subclinical Hyperthyroidism with the Risk of Cardiovascular Events and Cardiovascular Mortality: Meta-Analysis and Systematic Review of Cohort Studies

BACKGROUND: Whether hyperthyroidism is an independent risk factor for cardiovascular events remains controversial. We aimed to evaluate the association of overt and subclinical hyperthyroidism with the risk of ischemic heart disease (IHD), stroke, heart failure, and cardiovascular mortality. METHODS: Studies regarding the association between hyperthyroidism and cardiovascular events were searched on PubMed and Embase databases. The cardiovascular disease (CVD) risk was classified as high and low, based on pre-existing diseases, including history of coronary, cerebral, or peripheral artery disease; heart failure; atrial fibrillation; diabetes mellitus; or chronic kidney disease. RESULTS: Thirty-seven cohort studies were included in this meta-analysis. The pooled hazard ratio for subjects with overt hyperthyroidism compared with the control group was 1.11 (95% confidence interval [CI], 1.03 to 1.19) for IHD, 1.35 (95% CI, 1.03 to 1.75) for stroke, and 1.20 (95% CI, 1.00 to 1.46) for cardiovascular mortality. For subjects with subclinical hyperthyroidism, the pooled hazard ratio was 1.24 (95% CI, 1.07 to 1.45) for IHD, when compared with the control group. Subgroup analysis by CVD risk showed that the risk of stroke in overt hyperthyroidism was increased in the low CVD risk group; however, these association was not observed in the high CVD risk group. Similarly, the risk of IHD in subjects with subclinical hyperthyroidism was significantly increased in the low CVD risk group. CONCLUSION: Overt hyperthyroidism is associated with increased risk of IHD, stroke, and cardiovascular mortality, and subclinical hyperthyroidism is associated with increased risk of IHD. These associations were particularly observed in the low risk CVD group without underlying CVD.