Influence of cardiorespiratory fitness on obesity-associated inflammation in women and men: The FATCOR study.

BACKGROUND AND AIMS: Cardiorespiratory fitness has been postulated to lower chronic inflammation in obesity. We assessed sex-specific associations of inflammation with cardiorespiratory fitness in overweight and obese persons. METHODS AND RESULTS: Peak oxygen uptake (VO2max) was measured by treadmill in 566 participants (age 48 ± 9 years, 60% women) with body mass index >27.0 kg/m2 in the FAT associated CardiOvasculaR dysfunction (FATCOR) study. Fitness was identified from age- and sex specific reference levels of VO2max. The inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), kynurenine:tryptophan ratio (KTR) and pyriodoxic acid ratio (PAr) were measured by mass spectrometry. In the total study population 63% had obesity and 74% were cardiorespiratory unfit. Unfit women had the highest fat percentage and the highest serum levels of CRP and SAA (p < 0.05). In multivariable linear regression analyses in women, higher CRP (ß -0.15, p = 0.001), SAA (ß -0.10, p = 0.03) and PAr (ß -0.09, p = 0.03) were associated with lower VO2max after adjusting for confounders. In multivariable analyses in men, higher PAr (ß -0.14, p = 0.02) was associated with lower VO2max. In multivariable analyses in obese women, higher CRP and PAr remained associated with lower VO2max (p < 0.05), while in obese men there was no significant association. When normalizing VO2max for fat-free mass (VO2maxFFM) higher CRP, SAA and PAr index were associated with lower VO2maxFFM in women, while only higher PAr index was associated with lower VO2maxFFM in men. CONCLUSION: The association of inflammation with lower cardiorespiratory fitness was more pronounced in women than men, in particular when obesity was present. CLINICAL TRIAL REGISTRATION: URL: http://www. CLINICALTRIALS: gov NCT02805478.

Arterial Stiffness in Overweight and Obesity: Association with Sex, Age, and Blood Pressure.

INTRODUCTION: Obesity has been associated with increased arterial stiffness. Sex-differences in arterial stiffness in obesity have been less explored. AIM: To explore sex-differences in arterial stiffness by applanation tonometry in 323 women and 225 with overweight and obesity, free of cardiovascular disease. METHODS: Covariables of arterial stiffness were identified in multivariable linear regression analyses in the total cohort and separately in women and men. RESULTS: In the total study cohort, women had higher augmentation pressure (AP) and augmentation index (AIx), and lower carotid-femoral pulse wave velocity (cf-PWV) than men, independent of confounders (all p < 0.001). In sex-specific analyses, higher AP was associated with higher age and 24-hours systolic blood pressure (BP), and with lower heart rate in women (all p < 0.001), and with higher age and BP in men (all p < 0.001). Similarly, higher AIx was associated with higher age and BP, and lower body mass index (BMI) and heart rate in women (all p < 0.05), and with higher age in men (all p < 0.001). Higher cf-PWV correlated with higher age and BP in women (all p < 0.005), and additionally with higher heart rate and non-smoking in men (all p < 0.05). When replacing BMI with waist-hip ratio, higher waist-hip ratio was associated with higher cf-PWV in men only (p < 0.05). CONCLUSIONS: Among subjects with overweight and obesity, AP and AIx were higher in women, and cf-PWV was higher in men. Age and 24-hours systolic BP were the main factors associated with arterial stiffness in both sexes, while measures of adiposity had little impact on arterial stiffness.

Association of Myocardial Energetic Efficiency with Circumferential and Longitudinal Left Ventricular Myocardial Function in Subjects with Increased Body Mass Index (the FATCOR Study).

Lower myocardial mechanic-energetic efficiency (MEEi), expressed as stroke volume/heart rate ratio (SV/HR) in mL/s/g of the left ventricular (LV) mass, is associated with the incidence of heart failure in subjects with cardiometabolic disorders. We explored the association of MEEi with LV systolic circumferential and longitudinal myocardial function in 480 subjects with increased body mass index (BMI) without known cardiovascular disease (mean age 47 ± 9 years, 61% women, 63% obese, 74% with hypertension) participating in the fat-associated cardiovascular dysfunction (FATCOR) study. Insulin resistance was assessed by the homeostasis model assessment insulin-resistance index (HOMA-IR). SV was calculated by Doppler echocardiography. The LV systolic circumferential myocardial function was evaluated by midwall fractional shortening (MFS) and longitudinal function by global longitudinal strain (GLS). Patients were grouped into MEEi quartiles. The lowest MEEi quartile (<0.41 mL/s per g) was considered low MEEi. The association of MEEi with MFS and GLS were tested in multivariable linear regression analyses. Patients with low MEEi were more frequently men, with obesity and hypertension, dyslipidemia and higher HOMA-IR index (all p for trend <0.05). In multivariable analyses, lower MEEi was associated with lower LV myocardial function by MFS and GLS independent of higher LV mass and clinical variables, including older age, male sex, presence of hypertension and a higher triglycerides level (all p < 0.05). In conclusion, in subjects with increased BMI without known cardiovascular disease participating in the FATCOR study, reduced MEEi was associated with lower LV myocardial function both in the circumferential and longitudinal direction, independent of cardiometabolic factors.

Covariables of Myocardial Function in Women and Men with Increased Body Mass Index.

INTRODUCTION: Sex-difference in types of cardiac organ damage has been reported in subjects with increased body mass index (BMI). However less is known about sex-differences in left ventricular (LV) myocardial function assessed by global longitudinal strain (GLS) in these subjects. METHODS: 493 subjects (mean age 47 ± 9 years, 61% women) with BMI > 27.0 kg/m2 and without known cardiac disease underwent 24-hour (24h) ambulatory blood pressure (BP) recording, body composition analysis, carotid-femoral pulse wave velocity (PWV) measurement and echocardiography. LV peak systolic GLS was measured by two-dimensional speckle tracking echocardiography and LV ejection fraction (EF) by biplane Simpson's method. Insulin sensitivity was assessed by homeostatic model of insulin resistance (HOMA-IR). RESULTS: Women had higher prevalence of increased waist circumference (99% vs. 82%), lower prevalence of hypertension (59 vs. 74%), and lower serum triglycerides (1.3 ± 0.7 vs. 1.7 ± 0.9 mmol/L) and carotid-femoral PWV (7.3 ± 1.6 vs. 7.7 ± 1.6 m/s) compared to men (all p < 0.05). Women also had higher (more negative) GLS compared to men (- 19.9 ± 3.0 vs. - 18.6 ± 3.0%, p < 0.001), while EF did not differ between sexes. In multivariable linear regression analyses, lower GLS in women was associated with higher waist circumference and PWV and with lower EF (all p < 0.05). In men, lower GLS was associated with higher waist circumference and HOMA-IR, and with lower EF (all p < 0.05). CONCLUSIONS: Among subjects with increased BMI, GLS was higher in women than men. Lower GLS was associated with abdominal obesity in both sexes, and with impaired glucose metabolism in men, and with higher arterial stiffness in women. TRIAL REGISTRATION: https://www.clinicaltrials.gov NCT02805478, first registered 20.06.16.

Concomitant hypertension is associated with abnormal left ventricular geometry and lower systolic myocardial function in overweight participants: the FAT associated CardiOvasculaR dysfunction study.

OBJECTIVE: We studied the impact of concomitant hypertension on left ventricular (LV) systolic myocardial function and geometry in apparently healthy women and men with increased BMI. MATERIAL AND METHODS: We performed a cross-sectional analysis of 535 participants (59% women) with BMI greater than 27 kg/m without known cardiovascular disease enrolled in the FAT associated CardiOvasculaR dysfunction (FATCOR) study. Hypertension was defined as use of antihypertensive treatment or elevated 24-h ambulatory blood pressure. Abnormal LV geometry was identified as increased relative wall thickness and/or LV mass index. Systolic myocardial function was assessed by midwall shortening (MWS) and speckle tracking peak global longitudinal strain (GLS). RESULTS: Hypertensive participants were older (49 vs. 46 years), had higher BMI and waist circumference, higher prevalences of diabetes and abnormal LV geometry (29 vs. 16%), and lower GLS (-19 vs. -20%) and MWS (16.3 vs. 17.1%) compared with normotensive participants (all P < 0.01). In multivariable linear regression analyses, hypertension was associated with lower GLS (ß=0.11, P = 0.035) and lower MWS (ß=0.09, P = 0.029) independent of sex, diabetes, LV hypertrophy, ejection fraction, and waist circumference. Hypertension was also associated with presence of abnormal LV geometry [odds ratio 1.74 (95% confidence interval 1.04-2.89), P = 0.035) independent of the same confounders. When replacing waist circumference with BMI in the models, hypertension retained its association with lower myocardial function, whereas the association with abnormal LV geometry was attenuated. CONCLUSION: In participants with increased BMI without known clinical cardiovascular disease, concomitant hypertension was associated with lower systolic myocardial function and more abnormal LV geometry. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov NCT02805478.

Masked hypertension in obesity: potential predictors and arterial damage.

BACKGROUND: Masked hypertension (MHT), defined as normal office blood pressure (BP) but high ambulatory BP, has been associated with increased cardiovascular risk. Although MHT has been associated with obesity, there is limited knowledge on the prevalence and covariates of MHT in obese cohorts. METHODS: Office and ambulatory BP recordings and other cardiovascular risk factors were assessed in 323 obese participants included in the fat-associated cardiovascular dysfunction study (mean age 48.9±9.0 years, 55% women, mean BMI 32.3±4.4 kg/m). Office BP 130-139/85-89 mmHg was considered high-normal. Subclinical arterial damage was identified as carotid-femoral pulse wave velocity more than 10 m/s by applanation tonometry or carotid plaque by ultrasound (maximal intima-media thickness ≥1.5 mm). RESULTS: MHT was present in 17.1% of the population. Patients with MHT had a higher prevalence of metabolic syndrome, high-normal office BP, and were more often male compared with the normotensive (NT) individuals (all P<0.05), but were younger and had lower prevalence of diabetes and subclinical arterial damage than the sustained hypertensive group (all P<0.05). In multinomial logistic regression analysis, MHT was associated with the presence of metabolic syndrome and high-normal office BP compared with NT individuals, and lower pulse wave velocity and fewer carotid plaques than sustained hypertension (all P<0.05). CONCLUSION: In obese patients, MHT was associated with the presence of metabolic syndrome and high-normal office BP compared with NT individuals, but less subclinical arterial damage than sustained hypertensive patients.

Obesity-associated metabolic changes influence resting and peak heart rate in women and men.

OBJECTIVES: To study the relationship between obesity and heart rate (HR) in women and men. DESIGN: We studied 241 overweight and obese subjects without known heart disease. All subjects underwent ergospirometry during maximal exercise testing on treadmill and recording of body composition, electrocardiogram and clinic and ambulatory blood pressure. RESULTS: Women (n = 132) were slightly older and had higher fat mass, but lower weight, blood pressure and prevalence of metabolic syndrome (MetS) than men (n = 109) (all p < 0.05), while prevalences of obesity and hypertension did not differ. A significant interaction between sex and HR was demonstrated (p < 0.05). In multivariate analysis, female sex (ß = 0.99, p < 0.01) predicted higher resting HR independent of confounders. Higher resting HR was particularly associated with presence of MetS, hypertension, higher insulin resistance and lower relative muscle mass in men (all p < 0.05). Female sex also predicted higher peak exercise HR (ß = 0.48, p < 0.01) independent of confounders. Higher peak exercise HR was particularly associated with higher exercise capacity and lower age and self-reported physical activity in men, while lower HbA1c and absence of obesity were the main covariates in women in multivariate analyses (all p < 0.05). CONCLUSIONS: In our study population, obesity and obesity-associated metabolic changes influenced both resting and peak exercise HR.