Anita C. Bacher

Exaggerated Exercise Blood Pressure Is Related to Impaired Endothelial Vasodilator Function

BACKGROUND Persons with high normal blood pressure (BP) or mild hypertension who also have an exaggerated BP response to exercise are at risk for worsening hypertension. The mechanisms that explain this relationship are unknown. We examined the relationships of endothelial vasodilator function and of aortic stiffness with exercise BP. METHODS Subjects were 38 men and 44 women, aged 55 to 75 years, with untreated high normal BP or mild hypertension but otherwise healthy. Exercise was performed on a treadmill. Endothelial vasodilator function was assessed as brachial artery flow-mediated vasodilation (FMD) during reactive hyperemia. Aortic stiffness was measured as pulse wave velocity (PWV). RESULTS Among men, resting systolic BP explained 34% of the variance (P < .01) in maximal exercise systolic BP and FMD explained an additional 11% (P < .01); resting systolic BP explained 23% of the variance in maximal pulse pressure (PP) (P < .01), and FMD explained an additional 10% (P < .01). Among women, resting systolic BP was the only independent correlate of maximal systolic BP (R2 = 0.12, P < .03) and FMD correlated negatively with maximal PP (R2 = 0.12, P < .03). Among men, FMD was the only independent correlate of the difference between resting and maximal systolic BP (R2 = 0.20, P < .02). The FMD was the only independent correlate of the difference between resting and maximal PP among men (R2 = 0.17, P < .03) and among women (R2 = 0.12, P < .03). The PWV did not correlate with exercise BP responses. CONCLUSIONS These results suggest that impaired endothelial vasodilator function may be a mechanism contributing to exercise hypertension and may also be one link between exaggerated exercise BP and worsening hypertension.

Are fitness, activity, and fatness associated with health-related quality of life and mood in older persons?

PURPOSE This study sought to determine whether levels of fitness, habitual physical activity, and fatness are associated health-related quality of life and mood in older persons. METHODS The subjects were men (n = 38) and women (n = 44), ages 55 to 75 years, who had milder forms of hypertension, but who were otherwise healthy and not engaged in a regular exercise or diet program. Aerobic fitness was assessed by maximal oxygen uptake during treadmill testing, muscle strength by a one-repetition maximum, habitual activity by questionnaire, fatness by dual-energy x-ray absorptiometry, and body mass index. Health-related quality of life was assessed by the Medical Outcomes Study SF-36, and mood by the Profile of Mood States (POMS). Correlations were determined by bivariate and multivariate regression. RESULTS Higher aerobic fitness was associated with more desirable outcomes, as indicated by the POMS anger and total mood disturbance scores and by the SF-36 bodily pain, physical functioning, vitality, and physical component scores. Increased fatness was associated with less desirable outcomes, as indicated by the POMS anger, depression, and total mood disturbance scores and by the SF-36 bodily pain, physical functioning, role-emotional, role-physical, social functioning, vitality, and physical component scores. Higher physical activity was associated with an increased POMS score for vigor and a decreased SF-36 score for bodily pain. Strength was not related to health-related quality of life or mood. Aerobic fitness was the strongest predictor of the SF-36 score for vitality and the POMS score for total mood disturbance, whereas fatness was the strongest predictor of the POMS anger score and the SF-36 bodily pain, physical functioning, and physical component scores. CONCLUSIONS Even in the absence of regular exercise and a weight-loss diet, relatively small amounts of routine physical activity within a normal lifestyle, slight increases in fitness, and less body fatness are associated with a better health-related quality of life and mood.

Right Ventricular Dysfunction in Systemic Sclerosis–Associated Pulmonary Arterial Hypertension

Background—Systemic sclerosis–associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared with idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often caused by right ventricular (RV) failure. We tested whether SScPAH or systemic sclerosis–related pulmonary hypertension with interstitial lung disease imposes a greater pulmonary vascular load than IPAH and leads to worse RV contractile function. Methods and Results—We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 systemic sclerosis–related pulmonary hypertension with interstitial lung disease, and 67 IPAH). An inverse relation between pulmonary resistance and compliance was similar for all 3 groups, with a near constant resistance×compliance product. RV pressure–volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7), as well as SSc without PH (n=7) to derive contractile indexes (end-systolic elastance [Ees] and preload recruitable stroke work [Msw]), measures of RV load (arterial elastance [Ea]), and RV pulmonary artery coupling (Ees/Ea). RV afterload was similar in SScPAH and IPAH (pulmonary vascular resistance=7.0±4.5 versus 7.9±4.3 Wood units; Ea=0.9±0.4 versus 1.2±0.5 mm Hg/mL; pulmonary arterial compliance=2.4±1.5 versus 1.7±1.1 mL/mm Hg; P>0.3 for each). Although SScPAH did not have greater vascular stiffening compared with IPAH, RV contractility was more depressed (Ees=0.8±0.3 versus 2.3±1.1, P<0.01; Msw=21±11 versus 45±16, P=0.01), with differential RV-PA uncoupling (Ees/Ea=1.0±0.5 versus 2.1±1.0; P=0.03). This ratio was higher in SSc without PH (Ees/Ea=2.3±1.2; P=0.02 versus SScPAH). Conclusions—RV dysfunction is worse in SScPAH compared with IPAH at similar afterload, and may be because of intrinsic systolic function rather than enhanced pulmonary vascular resistive and pulsatile loading.

Usefulness of anthropometrics and dual-energy x-ray absorptiometry for estimating abdominal obesity measured by magnetic resonance imaging in older men and women

PURPOSE Increasing evidence suggests that abdominal obesity may be a better predictor of disease risk than total fatness. This study sought to determine how obesity and fat distribution measured by readily available anthropometric and dual-energy x-ray absorptiometry (DXA) methods is related to abdominal obesity assessed by magnetic resonance imaging (MRI). METHODS Men (n = 43) and women (n = 47), ages 55 to 75 years, were assessed for body mass index, waist-to-hip ratio, waist circumference, and skin folds by anthropometric methods; for percentage of body fat by DXA; and for abdominal total, subcutaneous, and visceral fat by MRI. RESULTS In stepwise regression models, the waist-to-hip ratio explained 50% of the variance in abdominal visceral fat among men (P <.01), and body mass index explained an additional 6% of the variance (P <.01). Among women, waist circumference was the only independent correlate of abdominal visceral fat, accounting for 52% of the variance (P <.01). Among men, the percentage of body fat was the only independent correlate of abdominal subcutaneous fat, explaining 65% of the variance (P <.01). Among women, the percentage of body fat explained 77% of the variance in abdominal subcutaneous fat and body mass index explained an additional 3% (P <.01). CONCLUSIONS Obesity and body composition obtained by readily available anthropometric methods and DXA provide informative estimates of abdominal obesity assessed by MRI imaging.

Exercise effects on cardiac size and left ventricular diastolic function: relationships to changes in fitness, fatness, blood pressure and insulin resistance

Objectives: To determine exercise training effects on cardiac size and left ventricular (LV) diastolic function and relationships of exercise induced changes in physiological and body composition parameters with cardiac parameters. Design: Prospective, randomised controlled trial. Subjects: Men and women (63.6 (5.7) years, body mass index 29.5 (4.4) kg/m2) with untreated hypertension (systolic blood pressure (BP) 130–159 or diastolic BP 85–99 mm Hg). Main outcome measures: Cardiac size and LV diastolic function, peak oxygen uptake (Vo2), muscle strength, general and abdominal fatness, and insulin resistance. Interventions: 6 months of exercise training versus usual care. Results: When analysed by group at six months, cardiac size and LV diastolic function did not differ between exercisers (n  =  51) and controls (n  =  53), whereas exercisers had significantly higher peak Vo2 (28 v 24 ml/kg/min) and strength (383 v 329 kg), and lower fatness (34% v 37%), diastolic BP (73 v 75 mm Hg) and insulin resistance (quantitative insulin sensitivity check index 0.35 v 0.34) versus controls (all p ⩽ 0.05). By regression analysis, among six month changes, increased peak Vo2 and reduced abdominal fat were associated with increased cardiac size. Increased peak Vo2 and reduced abdominal fat, BP and insulin resistance were associated with improved LV diastolic function. r Values ranged from 0.20 to 0.32 (p ⩽ 0.05). Conclusions: When examined by group assignment, exercise had no effect on cardiac size or LV diastolic function. When individual variations in six month changes were examined, participants attaining the greatest increases in fitness and reductions in abdominal fatness, insulin resistance and BP showed a modest trend towards physiological hypertrophy characterised by increased cardiac size and improved LV diastolic function. These results suggest that decreased abdominal fatness may have a role in improving cardiovascular health.

Exercise blood pressure response is related to left ventricular mass

An exaggerated SBP response to exercise has been associated with increased left ventricular (LV) mass in some but not all studies. A total of 43 women and 34 men, aged 55–75 years, without evidence of cardiovascular disease, with a mean resting BP of 142±9/77±8 mmHg had their BP measured at rest and during maximal treadmill exercise. LV mass was measured using magnetic resonance imaging. LV mass was adjusted for lean body mass, which was assessed by dual energy X-ray absorptiometry. LV mass was within the normal range for the majority of the subjects. Among the resting and exercise BP indices, maximal SBP was the strongest correlate of LV mass (r=0.41, P<0.05). In multivariate analysis, maximal SBP was independently associated with LV mass after adjustment for lean body mass and gender, explaining 3% of the variance (P<0.05). Maximal exercise SBP is a modest but still independent predictor of LV mass in older persons with normal LV mass. These results raise the possibility that the SBP response to maximal exercise is an early marker of LV hypertrophy.

Right Ventricular Functional Reserve in Pulmonary Arterial Hypertension

Background— Right ventricular (RV) functional reserve affects functional capacity and prognosis in patients with pulmonary arterial hypertension (PAH). PAH associated with systemic sclerosis (SSc-PAH) has a substantially worse prognosis than idiopathic PAH (IPAH), even though many measures of resting RV function and pulmonary vascular load are similar. We therefore tested the hypothesis that RV functional reserve is depressed in SSc-PAH patients. Methods and Results— RV pressure-volume relations were prospectively measured in IPAH (n=9) and SSc-PAH (n=15) patients at rest and during incremental atrial pacing or supine bicycle ergometry. Systolic and lusitropic function increased at faster heart rates in IPAH patients, but were markedly blunted in SSc-PAH. The recirculation fraction, which indexes intracellular calcium recycling, was also depressed in SSc-PAH (0.32±0.05 versus 0.50±0.05; P=0.039). At matched exercise (25 W), SSc-PAH patients did not augment contractility (end-systolic elastance) whereas IPAH did (P<0.001). RV afterload assessed by effective arterial elastance rose similarly in both groups; thus, ventricular-vascular coupling declined in SSc-PAH. Both end-systolic and end-diastolic RV volumes increased in SSc-PAH patients to offset contractile deficits, whereas chamber dilation was absent in IPAH (+37±10% versus +1±8%, P=0.004, and +19±4% versus –1±6%, P<0.001, respectively). Exercise-associated RV dilation also strongly correlated with resting ventricular-vascular coupling in a larger cohort. Conclusions— RV contractile reserve is depressed in SSc-PAH versus IPAH subjects, associated with reduced calcium recycling. During exercise, this results in ventricular-pulmonary vascular uncoupling and acute RV dilation. RV dilation during exercise can predict adverse ventricular-vascular coupling in PAH patients.

Decreased exercise blood pressure in older adults after exercise training: contributions of increased fitness and decreased fatness

Objective: To describe the contribution of changes in fitness and fatness resulting from exercise training on changes in submaximal exercise blood pressure (BP) during treadmill testing. Design and setting: Prospective, randomised, controlled trial. Participants: Sedentary older adults (n = 115) with untreated prehypertension or mild hypertension. Intervention: Six-month supervised aerobic and strength training. Main outcome measurement: Systolic BP (SBP) was assessed at rest and during each stage of a maximal graded exercise test (GXT) that determined Vo2peak. General and regional fatness was assessed by anthropometry, dual-energy x-ray absorptiometry and MRI. BP changes were calculated for each GXT stage, and multivariate regression models were used to describe the association of changes in exercise BP with changes in fitness and fatness. Results: After training, exercisers versus controls had significantly increased Vo2peak and significantly lower measures of general and regional fatness. Also, stage-specific SBP was significantly lower at stage 3 (−9.4 vs −1.6 mm Hg, p = 0.03) and stage 4 (−7.9 vs −1.2 mm Hg, p = 0.03). Pooled regression analysis across all stages showed that exercisers had a 7.1 mm Hg reduction in SBP, but this reduction fell short of statistical significance (p = 0.12) compared with controls. A 1.0 ml/kg/min increase in Vo2peak and a 1.0 cm decrease in waist circumference independently predicted a 1.0 mm Hg decrease in exercise SBP (p = 0.04 and p = 0.001, respectively). Conclusions: Decreased exercise SBP was independently associated with decreased waist circumference, a marker of abdominal obesity and increased fitness. These findings suggest that exercise training improves multiple factors that have an independent influence on SBP.

Relationships of Insulin Sensitivity with Fatness and Fitness and in Older Men and Women

PURPOSE Increased body fatness, especially abdominal obesity, and low levels of fitness are associated with decreased insulin sensitivity. Men and women differ in obesity, body fat distribution, and fitness levels. This cross-sectional study evaluated sex differences in the relationships of insulin sensitivity with fatness and fitness and obesity. METHODS Subjects were nonsmoking, nondiabetic, sedentary men (n = 50) and women (n = 61) aged 55-75 years with mild hypertension. Study measures were insulin sensitivity (QUICKI: 1/[log(fasting insulin) + log(fasting glucose)]), lipids and lipoproteins, total body fatness using dual energy x-ray absorptiometry (DXA), anthropometrics, abdominal obesity using magnetic resonance imaging (MRI), and aerobic fitness assessed as Vo(2) peak during treadmill testing. RESULTS Women had a higher percentage of body fat and more abdominal subcutaneous and less visceral fat than men. Among women, QUICKI correlated negatively with body mass index (BMI), percent body fat, abdominal total fat, subcutaneous fat, and visceral fat but not with lipids. Among men, QUICKI correlated negatively with total and abdominal fatness and triglycerides. QUICKI correlated with fitness in men only. Using stepwise regression, among women, decreased total abdominal fat accounted for 33%, and postmenopausal hormone therapy accounted for an additional 5% of the variance in QUICKI. Among men, only a higher level of fitness independently correlated with insulin sensitivity, accounting for 21% of the variance (p < 0.01). CONCLUSIONS Abdominal obesity among women and fitness among men were the strongest determinants of insulin sensitivity in this older cohort. This raises the question whether there are sex differences in the lifestyle changes that would be most effective in improving insulin sensitivity.