Female Sex and Angiotensin-Converting Enzyme (ACE) Insertion/Deletion Polymorphism Amplify the Effects of Adiposity on Blood Pressure
Authors: Chiriacò Martina , Tricò Domenico , Leonetti Simone , Petrie John R. , Balkau Beverley , Højlund Kurt , Pataky Zoltan , Nilsson Peter M , Natali Andrea , Heine R.J. , Dekker J. , de Rooij S. , Nijpels G. , Boorsma W. , Mitrakou A. , Tournis S. , Kyriakopoulou K. , Thomakos P. , Lalic N. , Lalic K. , Jotic A. , Lukic L. , Civcic M. , Nolan J. , Yeow T.P. , Murphy M. , DeLong C. , Neary G. , Colgan M.P. , Hatunic M. , Konrad T. , Böhles H. , Fuellert S. , Baer F. , Zuchhold H. , Golay A. , Harsch Bobbioni E. , Barthassat V. , Makoundou V. , Lehmann T.N.O. , Merminod T. , Perry C. , Neary F. , MacDougall C. , Shields K. , Malcolm L. , Laakso M. , Salmenniemi U. , Aura A. , Raisanen R. , Ruotsalainen U. , Sistonen T. , Laitinen M. , Saloranta H. , Coppack S.W. , McIntosh N. , Ross J. , Pettersson L. , Khadobaksh P. , Laville M. , Bonnet F. , Brac de la Perriere A. , Louche-Pelissier C. , Maitrepierre C. , Peyrat J. , Beltran S. , Serusclat A. , Gabriel R. , Sánchez E.M. , Carraro R. , Friera A. , Novella B. , Nilsson P. , Persson M. , Östling G. , Melander O. , Burri P. , Piatti P.M. , Monti L.D. , Setola E. , Galluccio E. , Minicucci F. , Colleluori A. , Walker M. , Ibrahim I.M. , Jayapaul M. , Carman D. , Ryan C. , Short K. , McGrady Y. , Richardson D. , Beck-Nielsen H. , Staehr P. , Vestergaard V. , Olsen C. , Hansen L. , Bolli G.B. , Porcellati F. , Fanelli C. , Lucidi P. , Calcinaro F. , Saturni A. , Ferrannini E. , Muscelli E. , Pinnola S. , Kozakova M. , Casolaro A. , Astiarraga B.D. , Mingrone G. , Guidone C. , Favuzzi A. , Di Rocco P. , Anderwald C. , Bischof M. , Promintzer M. , Krebs M. , Mandl M. , Hofer A. , Luger A. , Waldhäusl W. , Roden M. , Bonnet F. , Coppack S.W. , Dekker J.M. , Ferrannini E. , Mari A. , Petrie J. , Walker M. , Gaffney P. , Nolan J. , Boran G. , Olsen C. , Hansen L. , Beck-Nielsen H. , Kok A. , Dekker J. , Patel S. , Walker M. , Gastaldelli A. , Ciociaro D. , Kozakova M. , Guillanneuf M.T. , Mhamdi L. , Mari A. , Mhamdi L. , Landucci L. , Hills S. , Mota L. , Mari A. , Pacini G. , Cavaggion C. , Tura A. , Hills S.A. , Landucci L. , Mota L. 
Published: October 2021

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.