Satyam Sarma

Sympathetic vascular transduction is blunted in hypertensive adults relative to normotensive adults, which is in line with compensatory downregulation of vascular transduction to offset elevated sympathetic vasomotor outflow. The compensatory downregulation of sympathetic vascular transduction is less apparent in obesity-associated hypertension, despite no detectable difference in transduction to blood pressure between groups. Our data provide insight regarding differential sympathetic-vascular mechanisms of blood pressure control in adults with hypertension and obesity-associated hypertension.

This study shows that the oxygen cost of breathing is higher in patients with heart failure with preserved ejection fraction and obesity compared with healthy older adults without obesity but is not different from that of healthy older adults with obesity. A higher oxygen cost of breathing is further associated with a greater magnitude of obesity, more pronounced exertional dyspnea, and reduced exercise tolerance.

Background: Heart failure with preserved ejection fraction (HFpEF) is more prevalent in women than in men, and most patients with HFpEF are overweight or obese in the United States. However, whether the impact of obesity on autonomic dysregulation and inflammation differs by sex in HFpEF remains unknown. We investigated sex-specific associations between obesity, inflammation, and muscle sympathetic nerve activity (MSNA) in patients with HFpEF. Methods: In 57 HFpEF patients (mean±SD; 71±7 years; 37 women, 20 men) and 69 non-HFpEF controls (70±6 years; 43 women, 26 men), body mass index (BMI), MSNA, and C-reactive protein (CRP) were measured during supine rest. Results: A significant sex-by–BMI interaction was observed for the association between BMI and MSNA (Pinteraction=0.047), as well as BMI and CRP (Pinteraction=0.012). The slopes of these associations were steeper in women than men. Women with HFpEF had greater MSNA than men with HFpEF and control women (P<0.05); however, MSNA was not different between men with HFpEF and control men (P=0.727). The association between CRP and MSNA demonstrated a consistent trend toward sex-specificity (Pinteraction=0.060). In sex-stratified subgroup analyses of patients, MSNA and CRP were higher in women with high body fat assessed by DEXA than those with low body fat, but not in men. Conclusions: These findings identify a sex-specific association between obesity, inflammation, and sympathetic neural activity in HFpEF, characterized by a stronger obesity-related sympathetic activation in women. This pattern provides insight into the role of obesity-related inflammation as a key feature of disease expression in women with HFpEF.

Females with heart failure with preserved ejection fraction have lower muscle oxygen diffusive conductance during peak exercise compared with males. Interventions to improve muscle quality and diffusive capacity are of particular importance for improving peripheral limitations to exercise in females with HFpEF.

Background: Peak oxygen uptake (V̇O ₂ peak) is a strong predictor of survival in breast cancer survivors (BCS), with values ≤1.09 L/min associated with increased mortality. The relative contributions of convective oxygen delivery (QO ₂ ) and muscle oxygen diffusing capacity (D _M O ₂ ) to reduced V̇O ₂ peak in BCS remain unclear. Materials and Methods: In 49 BCS, we measured V̇O ₂ peak from cycle ergometry with gas-exchange analysis, and derived QO ₂ and D _M O ₂ using Fick-based calculations and computational modeling. BCS were stratified by mortality risk: High-Risk (V̇O ₂ peak ≤1.09 L/min; n=11) and Lower-Risk (n=38), and compared using t-tests, Mann-Whitney U tests and ANCOVA. Dominance analysis quantified the relative contributions of QO ₂ and D _M O ₂ to V̇O ₂ peak within each group. Results: The High-Risk group was older (72±6 vs. 69±5 years), had longer time since treatment (17±5 vs. 13±6 years), and higher cumulative doxorubicin-equivalent doses (291±134 vs. 163±120 mg/m²)(all p≤0.05). After ANCOVA, the High-Risk group had lower V̇O ₂ peak (1.0±0.1 vs. 1.4±0.2 L/min), QO ₂ (1.8±0.3 vs. 2.5±0.5 L/min), and D _M O ₂ (28.2±4.8 vs. 41.5±9.0 mL/min/mmHg) (all p≤0.001). Dominance analysis revealed D _M O ₂ as the strongest contributor to V̇O ₂ peak with 81.7% and 66.0% of explained variance in High-Risk and Lower-Risk groups while QO ₂ accounted for 14.1% and 30.3%, respectively. Conclusions: In older, long-term BCS with reduced V̇O ₂ peak (≤1.09 L/min), impairments in both QO ₂ and D _M O ₂ contribute to reduced exercise tolerance. However, D _m O ₂ emerged as the strongest modeled contributor in the high-risk group. Interventions prioritizing skeletal muscle–vascular function, alongside complementary targeting of QO ₂ , may have greater impact on V̇O ₂ peak improvements and survival in this high-risk population.

Sedentary ageing is linked to low cardiorespiratory fitness and the development of a small, stiff heart – risk factors for heart failure. Endurance exercise training reverses the effects of sedentary ageing on the heart when started in middle age; however, blunted training responses of females have been reported. Differences in baseline cardiac size or exercise‐induced cardiac remodelling may underly sex differences in trainability. Therefore, we investigated whether sex and left ventricular end‐diastolic volume indexed to body surface area (LV EDVi) influence the cardiovascular response to endurance training. Twenty‐eight sedentary adults [15 females; age: 54 ± 5 years, peak oxygen uptake (): 28.8 ± 4.8 mL min ⁻¹ kg ⁻¹ ) completed 2 years of training, with cardiorespiratory fitness and LV EDVi assessed following 10 months of progressive training and an additional 14 months of maintenance training. The increase in peak (sex × time: P < 0.001) of females after 2 years (∆ = 0.27 ± 0.14 L min ⁻¹ ) was ∼50% of the increase of males (∆ = 0.53 ± 0.20 L min ⁻¹ ), resulting from smaller increases in peak cardiac output (sex × time: P = 0.005) and stroke volume (sex × time: P = 0.013). However, LV EDVi at rest, an index of exercise‐induced cardiac remodelling, increased during the progressive training phase (main effect: P < 0.001) independent of sex (sex × time: P = 0.888) despite females having smaller EDVi throughout the study (main effect: P = 0.004). Males ( r = −0.650, P = 0.016) and females ( r = −0.776, P < 0.001) with the smallest initial resting LV EDVi experienced the greatest increase in EDVi with training. Overall, structured endurance exercise training in middle‐aged females resulted in blunted increases in cardiorespiratory fitness compared to males despite both sexes experiencing similar degrees of cardiac remodeling. image Key points: Endurance exercise training reverses the effects of sedentary ageing on the cardiovascular system if started in middle age, but the response to training could be modified by sex and baseline cardiac size and function We observed blunted increases in cardiorespiratory fitness of middle‐aged females compared to males with 2 years of endurance training, which were attributable to attenuated increases in peak stroke volume and cardiac output in females Both males and females experienced similar degrees of exercise‐induced cardiac remodelling, with people with the smallest hearts experiencing the greatest increase in left ventricular end‐diastolic volume index for each sex Our data demonstrate that the improvement in cardiorespiratory fitness with endurance exercise training is influenced by sex, but that the degree of cardiac remodelling with training in previously sedentary adults is not different between sexes, nor impaired by having a smaller pre‐training left ventricular end‐diastolic volume

Young healthy females have greater filling pressures during dynamic exercise relative to males. The augmented filling pressure in females points to a less distensible ventricle associated with smaller cardiac dimensions.