Matteo Landolfo (1), Francesco Spannella (2), Federico Giulietti (3), Alessandro Gezzi (2), Mirko Di Rosa (4), Luca Soraci (5), Riccardo Sarzani (6)

(1) Department of Clinical and Molecular Sciences (DISCLIMO), Centre of Obesity, University "Politecnica delle Marche“, Internal Medicine and Geriatrics, IRCSS INRCA, Ancona, Italy.
(2) Department of Clinical and Molecular Sciences (DISCLIMO), Centre of Obesity, University "Politecnica delle Marche“, Internal Medicine and Geriatrics, SISA LIPIGEN Centre, IRCCS INRCA, 60127 Ancona, Italy.
(3) Internal Medicine and Geriatrics, SISA LIPIGEN Centre, IRCCS INRCA, 60127 Ancona, Italy.
(4) Unit of Geriatric Pharmacoepidemiology and Biostatistics, IRCCS-INRCA, Ancona, Italy.
(5) 4Unit of Geriatric Medicine, IRCCS-INRCA, Cosenza, Italy.
(6) Department of Clinical and Molecular Sciences (DISCLIMO), Centre of Obesity, University "Politecnica delle Marche“, 1Internal Medicine and Geriatrics, IRCSS INRCA, Ancona, Italy.

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Background and aim: Insulin resistance (IR) is a dysmetabolic condition commonly associated with visceral adiposity that promotes dyslipidemia and higher blood pressure (BP) through multiple pathophysiological mechanisms. The triglycerides-HDL cholesterol ratio (TG/HDL-C), the TG/glucose index (TyGi) with the related TyGi body mass index (TyGi-BMI) and TyGi waist circumference (TyGi-WC) indexes, the lipid accumulation product (LAP), the visceral adiposity index (VAI), and the metabolic score for insulin resistance (METS-IR) are bio-anthropometric indexes of IR based on routinely available anthropometric and metabolic parameters that have been validated versus HOMA index. Regarding officeblood pressure (OBP), higher values of some of these indexes have been associated with an increased risk of hypertension and poor OBP control. However, no investigation has been conducted to study which IR surrogate indexes correlate with 24-hour ambulatory BP monitoring (ABPM), and data on anti-hypertensive treatment in real-life patients is lacking. Our study evaluated the association between IR bio-anthropometric indexes with hypertension and uncontrolled 24-hour BP based on ABPM cutoffs in a non-diabetic outpatient population.

Methods: An observational cross-sectional study on 1336 consecutive outpatients evaluated for hypertension at our ESH Hypertension Excellence Centre, Internal Medicine and Geriatric Unit, IRCCS-INRCA Ancona, Italy, and who had a recent and valid ABPM available. TG/HDL-C, TyGi-BMI, TyGi-WC, LAP, VAI, and METS-IR were calculated based on available anthropometric and metabolic parameters. Anti-hypertensive therapies were assessed by considering the number of drugs and dosages and using the treatment intensity score (TIS), calculated as the ratio of the administered dose to the maximum dose. Multivariate logisticregression models (Model 1: adjusted for age and sex; Model 2: further adjusted for antihypertensive treatment, and Model 3 further adjusted for anti-hypertensive medications and TIS) were used to evaluate the association between IR bio-anthropometric indexes quartiles (referenced to the first quartile) and the prevalence of hypertension and uncontrolled 24-hour BP, in the overall population and subgroups based on the anti-hypertensive and lipid-lowering therapies (CLT), sex, and age.

Results: Mean age of 54.9 ± 13.7 years and male prevalence (58.3%) with a mean body mass index (BMI) of 27.4 ± 4.4 kg/m 2 . Sixty-nine per cent were on anti-hypertensive treatment(s), predominantly renin-angiotensin system inhibitors (RASi, 70.7%). The median TG/HDL-C ratio was 2.07 (IQR 1.4-3.3), the median TyGi-BMI was 234.9 (IQR 209.7-267.1), the median TyGi-WC was 832.8 (IQR 758.9-927.8), the median LAP was 41.4 (27.6-65), the median VAI was 71.3 (IQR 47-115.9), and the median METS-IR was 41 (IQR 36-47). The median number of anti-hypertensive drugs was 2 (IQR 1-3), and the median TIS was 1.11 (IQR 0.75-2). BP values of hypertension based on ABPM criteria were found in 64.2% (n = 858) despite therapy. Patients with hypertension and uncontrolled 24-hour BP were younger, predominantly male, with lower rates of cardiovascular comorbidities and related treatments, and with higher values of IR indexes. Higher METS-IR and TyGi-BMI quartiles were independently associated with an increased risk of hypertension and uncontrolled 24-hour BP compared to the first quartile in the unadjusted and adjusted models. The sensitivity analyses in the subgroups confirmed the potential usefulness of METS-IR and TyGi-BMI in predicting hypertension and uncontrolled 24-hour BP, regardless of cholesterol-lowering therapy (CLT), sex, and age.

Conclusions: METS-IR and TyGi-BMI were the best predictors of hypertension and uncontrolled 24-hour BP, even in patients on antihypertensive treatment and regardless of CLT, sex, and age. IR bio-anthropometric indexes based on low-cost and generally available anthropometric and metabolic parameters might identify real-life overweight or obese patients with an adipo-centric dysmetabolic higher risk of hypertension and uncontrolled 24-hour BP.