Sex differences in the physiological responses to cardiac rehabilitation: a systematic review.

BACKGROUND: Heart disease is one of the leading causes of death in Canada. Many heart disease patients are referred for cardiac rehabilitation, a multidisciplinary outpatient program often consisting of exercise training. Cardiac rehabilitation has been proven to be a successful secondary preventative measure in reducing mortality and improving overall health in heart disease patients, and its completion is important for both sexes as there is growing evidence that women benefit as much as men, if not more, with regard to mortality. It is important to note that previous studies have shown that healthy men and women respond differently to aerobic and resistance training, possibly due to hormones, body composition, autonomic and/or cardiovascular differences. However, evaluating sex differences in the efficacy of standard cardiac rehabilitation programs has not yet been fully explored with many studies investigating clinical or anthropometric data but not physiological outcomes. This systematic review aimed to investigate physiological differences in male and female heart disease patients after cardiac rehabilitation. The inclusion criteria were purposefully broad to encompass many cardiac rehabilitation scenarios, many cardiac disease states, and various program lengths and intensities with the intention of highlighting strengths and weaknesses of the current body of literature. METHODS: To conduct a synthesis without meta-analysis, a search strategy was generated to examine the relationships between heart disease patients, a supervised exercise program, physiological outcomes, and sex differences. The review was registered (Prospero: CRD42021251614) and the following databases were searched from inception to 19 December 2023: APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), Embase (Ovid), Emcare Nursing (Ovid), Medline All (Ovid; includes PubMed non-Medline), and Web of Science Core Collection. Eighty-eight studies pertaining to fitness, metabolism, body composition, respiratory function, cardiac function and C-reactive protein underwent data extraction. RESULTS AND CONCLUSIONS: Importantly, this review suggests that men and women respond similarly to a wide-range of cardiac rehabilitation programs in most physiological variables. However, many studies discussing maximal oxygen consumption, functional capacity, six-minute walk distances, and grip strength suggest that men benefit more. Further research is required to address certain limitations, such as appropriate statistical methods and type/intensity of exercise interventions.

The effects of oral contraceptives on resting autonomic function and the autonomic response to physiological stressors: a systematic review.

PURPOSE: This systematic review aimed to summarize how oral contraceptives (OC) affect resting autonomic function and the autonomic response to a variety of physiological stressors. METHODS: A search strategy was created to retrieve citations investigating physiological responses comparing OC users to non-users (NOC) in response to autonomic reflex activation. RESULTS: A total of 6148 citations were identified across databases from inception to June 2, 2022, and 3870 citations were screened at the abstract level after deduplication. Then, 133 texts were assessed at full-text level, and only 40 studies met eligibility requirements. Included citations were grouped by the aspect of autonomic function assessed, including autonomic reflex (i.e., baroreflex, chemoreflex, mechanoreflex, metaboreflex, and venoarterial reflex), or indicators (i.e., heart rate variability, pulse wave velocity, and sympathetic electrodermal activity), and physiological stressors that may alter autonomic function (i.e., auditory, exercise, mental or orthostatic stress, altitude, cold pressor test, sweat test, and vasodilatory infusions). CONCLUSION: OC influence the physiological responses to chemoreflex, mechanoreflex, and metaboreflex activation. In terms of autonomic indices and physiological stressors, there are more inconsistencies within the OC literature, which may be due to estrogen dosage within the OC formulation (i.e., heart rate variability) or the intensity of the stressor (exercise intensity/duration or orthostatic stress). Further research is required to elucidate the effects of OC on these aspects of autonomic function because of the relatively small amount of available research. Furthermore, researchers should more clearly define or stratify OC use by duration, dose, and/or hormone cycling to further elucidate the effects of OC.

Oral contraceptive use and menstrual cycle influence acute cerebrovascular response to standing.

PURPOSE: To determine if the menstrual cycle and oral contraceptives (OC) influence responses to acute orthostatic stress and if these factors are clinically relevant to the diagnosis of initial orthostatic hypotension (iOH). METHODS: Young, healthy women were recruited, including OC users (n = 12) and non-users (NOC; n = 9). Women were tested during the low hormone (LH; placebo pills; days 2-5 natural cycle) and high hormone (HH; active dose; days 18-24 natural cycle) menstrual phases. Changes in mean arterial pressure, cardiac output, heart rate, the 30:15 heart rate ratio and cerebrovascular resistance indices within 30 s of standing were examined. RESULTS: There were no effects of OC or menstrual cycle on hemodynamic responses during standing (all p>0.05). In the LH phase, OC users had a greater fall in mean middle cerebral artery blood velocity (MCAV) compared to NOC (p<0.05). However, this was reversed in the HH phase, where OC users had a reduced fall in mean MCAV (p<0.05). Interestingly, 8 women (OC and NOC) had drops in systolic/diastolic blood pressure meeting the criteria for iOH, and 7 of those 8 women displayed this drop in a single phase of the menstrual cycle. CONCLUSION: Our results indicate that chronic versus acute OC use (i.e., long-term use observed via LH phase versus short-term use observed via HH phase) have opposing effects on cerebral blood velocity during standing. Further, our results highlight that multiple assessments across the cycle may be necessary to accurately diagnose iOH, as most women met the diagnostic criteria during a single menstrual phase.

Factors associated with complementary and alternative medicine use among women at midlife.

Hormone replacement therapy (HRT) has been established as the first-line treatment for women experiencing menopausal symptoms. The use of complementary and alternative medicine (CAM), however, is becoming increasingly popular among women at midlife for management of such symptoms. Despite the equivocal evidence of CAM's efficacy in the reduction and alleviation of menopausal symptoms in placebo-controlled, randomized trials, 50% of women at midlife use CAM. To date, several large, population-based studies have focused upon CAM use amongst menopausal women and the factors associated with the adoption of such therapies. By identifying women in the menopausal transition who tend to use CAM, this narrative review highlights evidence that aids women at this stage of life make better and individualized treatment choices to relieve these symptoms. The available evidence suggests that the prevalence of CAM use among menopausal women is high world-wide, but there is a paucity of high-quality studies that adequately assess the factors associated with its use. Further studies are needed to confirm the characteristics of women who employ CAM to manage their night sweats and hot flushes. Results of this study might enable the development of policies catering to the needs of those women and provide a resource to support their decision-making regarding treatment options.

Activation of the carotid chemoreflex secondary to muscle metaboreflex stimulation in men.

Recent work has shown that the carotid chemoreceptor (CC) contributes to sympathetic control of cardiovascular function during exercise, despite no evidence of increased circulating CC stimuli, suggesting enhanced CC activity/sensitivity. As interactions between metaboreceptors and chemoreceptors have been previously observed, the purpose of this study was to isolate the metaboreflex while acutely stimulating or inhibiting the CC to determine whether the metaboreflex increased CC activity/sensitivity. Fourteen young healthy men (height: 177.0 ± 2.1 cm, weight: 85.8 ± 5.5 kg, age: 24.6 ± 1.1 yr) performed three trials of 40% maximal voluntary contraction handgrip for 2 min, followed by 3 min of postexercise circulatory occlusion (PECO) to stimulate the metaboreflex. In random order, subjects either breathed room air, hypoxia (target SPo2 = 85%), or hyperoxia (FiO2 = 1.0) during the PECO to modulate the chemoreflex. After these trials, a resting hypoxia trial was conducted without handgrip or PECO. Ventilation (Ve), heart rate (HR), blood pressure, and muscle sympathetic nervous activity (MSNA) data were continuously obtained. Relative to normoxic PECO, inhibition of the CC during hyperoxic PECO resulted in lower MSNA (P = 0.038) and HR (P = 0.021). Relative to normoxic PECO, stimulation of the CC during hypoxic PECO resulted in higher HR (P < 0.001) and Ve (P < 0.001). The ventilatory and MSNA responses to hypoxic PECO were not greater than the sum of the responses to hypoxia and PECO individually, indicating that the CC are not sensitized during metaboreflex activation. These results demonstrate that stimulation of the metaboreflex activates, but does not sensitize the CC, and help explain the enhanced CC activity with exercise.

Cardiovascular responses to lower body negative pressure before and after 4 h of head-down bed rest and seated control in men and women.

Cardiovascular deconditioning after a 4-h head-down bed rest (HDBR) might be a consequence of the time of day relative to pre-HDBR testing, or simply 4 h of confinement and inactivity rather than the posture change. Ten men and 11 women were studied during lower body negative pressure (LBNP) before and after 4-h HDBR and 4-h seated posture (SEAT) as a control for time of day and physical inactivity effects to test the hypotheses that cardiovascular deconditioning was a consequence of the HDBR posture, and that women would have a greater deconditioning response. Following HDBR, men and women had lower blood volume, higher heart rate with a greater increase during LBNP, a greater decrease of stroke volume during LBNP, lower central venous pressure, smaller inferior vena cava diameter, higher portal vein resistance index with a greater increase during LBNP, but lower forearm vascular resistance, lower norepinephrine, and lower renin. Women had lower vasopressin and men had higher vasopressin after HDBR, and women had lower pelvic impedance and men higher pelvic impedance. Following SEAT, brachial vascular resistance was reduced, thoracic impedance was elevated, the reduction of central venous pressure during LBNP was changed, women had higher angiotensin II whereas men had lower levels, and pelvic impedance increased in women and decreased in men. Cardiovascular deconditioning was greater after 4-h HDBR than after SEAT. Women and men had similar responses for most cardiovascular variables in the present study that tested the responses to LBNP after short-duration HDBR compared with a control condition.

WISE 2005: responses of women to sublingual nitroglycerin before and after 56 days of 6° head-down bed rest.

This study tested the hypothesis that cardiovascular effects of sublingual nitroglycerin (NG) would be exaggerated after 56 days of 6° head-down bed rest (HDBR) in women, and that an aerobic and resistive exercise countermeasure (EX, n = 8) would reduce the effect compared with HDBR without exercise (CON, n = 7). Middle cerebral artery maximal blood flow velocity (CBFV), cardiac stroke volume (SV), and superficial femoral artery blood flow (Doppler ultrasound) were recorded at baseline rest and for 5 min following 0.3 mg sublingual NG. Post-HDBR, NG caused greater increases in heart rate (HR) in CON compared with EX (+24.9 ± 7.7 and +18.8 ± 6.6 beats/min, respectively, P < 0.0001). The increase in HR combined with reductions in SV to maintain cardiac output. Systolic, mean, and pulse pressures were reduced 5-10 mmHg by NG, but total peripheral resistance was only slightly reduced at 3 min after NG. Reductions in CBFV of -12.5 ± 3.8 cm/s were seen after NG, but a reduction in the Doppler resistance index suggested dilation of the middle cerebral artery with no differences after HDBR. The femoral artery dilated with NG and blood flow was reduced ∼50% with the appearance of large negative waves suggesting a marked increase in downstream resistance, but there were no effects of HDBR. In general, responses of women to NG were not altered by HDBR; the greater increase in HR in CON but not EX was probably a consequence of cardiovascular deconditioning. These results contrast with the hypothesis and a previous investigation of men after HDBR by revealing no change in cardiovascular responses to exogenous nitric oxide.

Central versus peripheral cardiovascular risk in metabolic syndrome.

Individuals with metabolic syndrome (MetS; i.e., three of five of the following risk factors (RFs): elevated blood pressure, waist circumference, triglycerides, blood glucose, or reduced HDL) are thought to be prone to serious cardiovascular disease and there is debate as to whether the disease begins in the peripheral vasculature or centrally. This study investigates hemodynamics, cardiac function/morphology, and mechanical properties of the central (heart, carotid artery) or peripheral [total peripheral resistance (TPR), forearm vascular bed] vasculature in individuals without (1-2 RFs: n = 28), or with (≥3 RFs: n = 46) MetS. After adjustments for statin and blood pressure medication use, those with MetS had lower mitral valve E/A ratios (<3 RFs: 1.24 ± 0.07; ≥3 RFs: 1.01 ± 0.04; P = 0.025), and higher TPR index (<3 RFs: 48 ± 2 mmHg/L/min/m(2); ≥3 RFs: 53 ± 2 mmHg/L/min/m(2); P = 0.04). There were no differences in heart size, carotid artery measurements, cardiovagal baroreflex, pulse-wave velocity, stroke volume index, or cardiac output index due to MetS after adjustments for statin and blood pressure medication use. The use of statins was associated with increased inertia in the brachial vascular bed, increased HbA1c and decreased LDL cholesterol. The independent use of anti-hypertensive medication was associated with decreased predicted [Formula: see text] triglycerides, diastolic blood pressure, interventricular septum thickness, calculated left ventricle mass, left ventricle posterior wall thickness, and left ventricle pre-ejection period, but increased carotid stiffness, HDL cholesterol, and heart rate. These data imply that both a central cardiac effect and a peripheral effect of vascular resistance are expressed in MetS. These data also indicate that variance in between-group responses due to pharmacological treatments are important factors to consider in studying cardiovascular changes in these individuals.

Hemodynamics and brain blood flow during posture change in younger women and postmenopausal women compared with age-matched men.

Increased incidence of orthostatic hypotension and presyncopal symptoms in young women could be related to hormonal factors that might be isolated by comparing cardiovascular and cerebrovascular responses to postural change in young and older men and women. Seven young women, 11 young men, 10 older women (>1 yr postmenopausal, no hormone therapy), and 9 older men participated in a supine-to-sit-to-stand test while measuring systemic hemodynamics, end-tidal Pco(2), and blood flow velocity of the middle cerebral artery (MCA). Women had a greater reduction in stroke volume index compared with age-matched men (change from supine to standing: young women: -22.9 ± 1.6 ml/m(2); young men: -14.4 ± 2.4 ml/m(2); older women: -17.4 ± 3.3 ml/m(2); older men: -13.8 ± 2.2 ml/m(2)). This was accompanied by offsetting changes in heart rate, particularly in young women, resulting in no age or sex differences in cardiac output index. Mean arterial pressure (MAP) was higher in older subjects and increased with movement to upright postures. Younger men and women had higher forearm vascular resistance that increased progressively in the upright posture compared with older men and women. There was no difference between sexes or ages in total peripheral resistance index. Women had higher MCA velocity, but both sexes had reduced MCA velocity while upright, which was a function of reduced blood pressure at the MCA and a significant reduction in end-tidal Pco(2). The reductions in stroke volume index suggested impaired venous return in women, but augmented responses of heart rate and forearm vascular resistance protected MAP in younger women. Overall, these results showed significant sex and age-related differences, but compensatory mechanisms preserved MAP and MCA velocity in young women.

WISE 2005: vascular responses to 60-day bed rest in women.

WISE-2005 studied 24 women during a 60-day head down bed rest (HDBR) who look part in an exercise countermeasure (LBNP-treadmill plus flywheel, EX) and no-exercise (No-EX). We conducted a series of experiments to explore changes in cardiovascular function and the ability of EX to prevent these changes. Resting arterial diameter in the arm was not affected but the leg arteries (femoral and popliteal) were significantly reduced in Np-EX, but was increased in EX. In this study we report on drug stimulated responses with sublingual nitroglycerin and infused isoproterenol. Heart rate increased in response to nitroglycerin with larger increases in No-EX after HDBR. Likewise during isoproterenol infusion the HR increase was greater after HDBR in the No-EX group. In all cases, the higher HR was associated with lower stroke volume in No-EX while stroke volume was protected in EX. These data do not support a change in sensitivity of beta-adrenergic receptors after HDBR. The leg vascular resistance decreased in response to isoproterenol and it decreased to a greater extent in No-EX than EX. These data were consistent with observations of lower leg vascular resistance during orthostatic challenge tests after HDBR. We conclude that consistent changes in cardiovascular function in the No-EX were detected by different methods that point to mechanisms contributing to orthostatic intolerance after HDBR.