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Female Sex and Angiotensin-Converting Enzyme (ACE) Insertion/Deletion Polymorphism Amplify the Effects of Adiposity on Blood Pressure.

Metabolism, Nutrition, and Atherosclerosis Laboratory, Department of Clinical and Experimental Medicine (M.C., D.T., S.L., A.N.), University of Pisa, Italy. Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine (D.T.), University of Pisa, Italy. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.R.P.). Clinical Epidemiology, CESP, University Paris-Saclay, UVSQ, University Paris-Sud, Inserm U1018, Villejuif, France (B.B.). Steno Diabetes Center Odense, Odense University Hospital, Denmark (K.H.). Division of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, WHO Collaborating Centre, University Hospitals of Geneva, University of Geneva, Switzerland (Z.P.). Department of Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden (P.M.N.).

Hypertension (Dallas, Tex. : 1979). 2022;(1):36-46
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Abstract

The pathophysiological link between adiposity and blood pressure is not completely understood, and evidence suggests an influence of sex and genetic determinants. We aimed to identify the relationship between adiposity and blood pressure, independent of a robust set of lifestyle and metabolic factors, and to examine the modulating role of sex and Angiotensin-Converting Enzyme (ACE) insertion/deletion (I/D) polymorphisms. In the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) study cohort, 1211 normotensive individuals, aged 30 to 60 years and followed-up after 3.3 years, were characterized for lifestyle and metabolic factors, body composition, and ACE genotype. Body mass index (BMI) and waist circumference (WC) were independently associated with mean arterial pressure, with a stronger relationship in women than men (BMI: r=0.40 versus 0.30; WC: r=0.40 versus 0.30, both P<0.01) and in individuals with the ID and II ACE genotypes in both sexes (P<0.01). The associations of BMI and WC with mean arterial pressure were independent of age, sex, lifestyle, and metabolic variables (standardized regression coefficient=0.17 and 0.18 for BMI and WC, respectively) and showed a significant interaction with the ACE genotype only in women (P=0.03). A 5 cm larger WC at baseline increased the risk of developing hypertension at follow-up only in women (odds ratio, 1.56 [95% CI, 1.15-2.10], P=0.004) and in II genotype carriers (odds ratio, 1.87 [95% CI, 1.09-3.20], P=0.023). The hypertensive effect of adiposity is more pronounced in women and in people carrying the II variant of the ACE genotype, a marker of salt sensitivity.