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Assessing the Causal Role of BMI on Cardiovascular Health in Young Adults
abstract
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Access this abstract nowBackground
Body mass index (BMI) has been suggested to be causally related to cardiovascular health in mid-to-late life, but this has not been explored systematically at younger ages—nor with detailed cardiovascular phenotyping. Recall-by-Genotype (RbG) is an approach that enables the collection of precise phenotypic measures in smaller studies, while maintaining statistical power and ability for causal inference.
Methods
In this study, we used a combination of conventional multivariable regression analysis, Mendelian randomization (MR), and subsample RbG methodologies to estimate the causal effect of BMI on gross-level and detailed cardiovascular health in healthy participants from the Avon Longitudinal Study of Parents and Children at age 17 years (N=1420–3108 for different outcomes) and an independent sample from the same cohort (for RbG) study at age 21 years (N=386–418).
Results
In both MR and RbG analyses, results suggested that higher BMI causes higher blood pressure and left ventricular mass index in young adults (eg, difference in left ventricular mass index per 1 kg/m2 using MR: 1.07 g/m2.7; 95% CI, 0.62–1.52; P=3.87×10-06 and per 3.58 kg/m2 using RbG: 1.65 g/m2.7; 95% CI, 0.83–2.47; P=0.0001). Additionally, RbG results suggested a causal role of higher BMI on higher stroke volume (difference per 3.58 kg/m2: 1.49 mL/m2.04; 95% CI, 0.62–2.35; P=0.001) and cardiac output (difference per 3.58 kg/m2: 0.11 L·min-1·m-1.83; 95% CI, 0.03–0.19; P=0.01) but no strong evidence for a causal role on systemic vascular resistance or total arterial compliance. Neither analysis supported a causal role of higher BMI on heart rate.
Conclusions
Complementary MR and RbG causal methodologies, together with a range of sensitivity analyses, suggest that higher BMI is likely to cause worse cardiovascular health, specifically higher blood pressure and left ventricular mass index, even in youth. Higher BMI also resulted in increased cardiac output in the RbG study, which appeared to be solely driven by stroke volume, as neither MR nor RbG analyses suggested a causal effect of BMI on heart rate. These consistent results support efforts to reduce BMI from a young age to prevent later adverse cardiovascular health and illustrate the potential for phenotypic resolution with maintained analytic power using RbG.
While there has been an ongoing debate about the utility of body mass index (BMI) as a measure to define obesity, numerous clinical studies have demonstrated that adults with a high BMI are more likely to have poorer health outcomes and chronic disease. Severe obesity in childhood, adolescence, and young adulthood leads to poor cardiometabolic health outcomes such as impairment of cardiac structure and function and hypertension.
This study by Wade and colleagues utilizes multivariable regression analysis, Mendelian randomization (MR), and Recall-by-Genotype (RbG), an approach that enables the collection of phenotypic measures in small studies to determine the impact of BMI on cardiovascular health in healthy participants at 17 and 21 years of age in the Avon Longitudinal Study of Parents and Children. Their analysis suggests that higher BMI is likely to lead to worse cardiovascular health, particularly increased blood pressure and left ventricular mass. This is yet another study which supports early intervention and treatment of adolescents and young adults with obesity to improve overall health. Although BMI may not be a perfect measure of obesity, it does allow us to stratify at-risk individuals to support improved cardiovascular health by appropriate treatment of their obesity.