Abstract
Aims/HypothesisWe aimed to explore whether and to what extent overweight or obesity could increase the risk of hypertension, and further to estimate the roles of genetic and early-life familial environmental factors in their association.MethodsThis prospective twin study was based on the Chinese National Twin Registry (CNTR), which collected information from self-report questionnaires. We conducted unmatched case-control analysis to examine the association between overweight or obesity and hypertension. And further to explore whether genetics and familiar environments shared within a twin pair, accounted for their association via co-twin matched case-control design. Generalized estimating equation (GEE) models and conditional logistic regressions were used in the unmatched and matched analyses, respectively. Then, we used logistic regressions to test the difference in odds ratios (ORs) between the unmatched and matched analyses. Finally, through bivariate twin model, the roles of genetic and environmental factors in the body mass index (BMI)- hypertension association were estimated.ResultsOverall, we included a total of 30,617 twin individuals, of which 7533 (24.6%) twin participants were overweight or obesity and 757 (2.5%) developed hypertension during a median follow-up time of 4.4 years. In the GEE model, overweight or obesity was associated with a 94% increased risk of hypertension (OR=1.94, 95% confidence interval (CI): 1.64~2.30). In the conditional logistic regression, the multi-adjusted OR was 1.80 (95% CI: 1.18~2.74). The difference in OR between unmatched and matched analyses was significant (P=0.016). Specifically, overweight or obesity was not associated with hypertension risk in the co-twin design when we full controlled genetic and familiar environmental factors (OR=0.89, 95 CI: 0.46~1.72). After controlling for age and sex, we found the positive BMI-hypertension association was mainly explained by a genetic correlation between them (r A= 0.59, 95% CI: 0.44~1.00).Conclusions/InterpretationGenetics and early-life environments shared by participants within a twin pair appear to account for the association between overweight or obesity and hypertension risk.
Highlights
Raised blood pressure remains the leading cause of death globally, high systolic blood pressure accounted for 10·8 million deaths in 2019 [1]
In the multi-adjusted conditional logistic regression, overweight or obesity was associated with an 80% higher hypertension risk (OR=1.80, 95% CI: 1.18~2.74)
In the matched analysis of DZ twins, controlling 50% genetic factors, overweight or obesity increased the risk of hypertension under the control of confounders (OR=2.86, 95% CI: 1.57~5.21)
Summary
Raised blood pressure remains the leading cause of death globally, high systolic blood pressure accounted for 10·8 million deaths in 2019 [1]. In the original Framingham cohort, Wilson et al [4] found overweight and obese status were associated with increased risk of hypertension: the multiadjusted risk ratios (RRs) among the overweight was 1.48 in men and 1.70 in women, while among the obese was 2.23 in men and 2.63 in women. In another Framingham study, weight loss led to a 21%~29% reduction in long-term hypertension risk [5]. Mendelian randomization (MR) analysis, using genetic variants as the instrumental variable, has demonstrated the causality between obesity and hypertension [6]
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