The Effect of Gender-Affirming Hormone Therapy on the Risk of Subclinical Atherosclerosis in the Transgender Population: A Systematic Review.

OBJECTIVE: The impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT. METHODS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with CV risk were included. RESULTS: From 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity, and decreased vasodilation. Studies of trans women receiving GAHT reported decreased interleukin 6, plasminogen activator inhibitor-1, and tissue plasminogen activator levels and brachial-ankle pulse wave velocity, with variations in flow-mediated dilation and arterial stiffness depending on the type of treatment and route of administration. CONCLUSIONS: The results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of CV disease in the transgender population receiving GAHT. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42022323757.

The "Hypertension Approaches in the Elderly: a Lifestyle study" multicenter, randomized trial (HAEL Study): rationale and methodological protocol.

BACKGROUND: Hypertension is a clinical condition highly prevalent in the elderly, imposing great risks to cardiovascular diseases and loss of quality of life. Current guidelines emphasize the importance of nonpharmacological strategies as a first-line approach to lower blood pressure. Exercise is an efficient lifestyle tool that can benefit a myriad of health-related outcomes, including blood pressure control, in older adults. We herein report the protocol of the HAEL Study, which aims to evaluate the efficacy of a pragmatic combined exercise training compared with a health education program on ambulatory blood pressure and other health-related outcomes in older individuals. METHODS: Randomized, single-blinded, multicenter, two-arm, parallel, superiority trial. A total of 184 subjects (92/center), ≥60 years of age, with no recent history of cardiovascular events, will be randomized on a 1:1 ratio to 12-week interventions consisting either of a combined exercise (aerobic and strength) training, three times per week, or an active-control group receiving health education intervention, once a week. Ambulatory (primary outcome) and office blood pressures, cardiorespiratory fitness and endothelial function, together with quality of life, functional fitness and autonomic control will be measured in before and after intervention. DISCUSSION: Our conceptual hypothesis is that combined training intervention will reduce ambulatory blood pressure in comparison with health education group. Using a superiority framework, analysis plan prespecifies an intention-to-treat approach, per protocol criteria, subgroups analysis, and handling of missing data. The trial is recruiting since September 2017. Finally, this study was designed to adhere to data sharing practices. TRIAL REGISTRATION: NCT03264443 . Registered on 29 August, 2017.

Yoga and breathing technique training in patients with heart failure and preserved ejection fraction: study protocol for a randomized clinical trial.

BACKGROUND: Current therapies for heart failure (HF) are followed by strategies to improve quality of life and exercise tolerance, besides reducing morbidity and mortality. Some HF patients present changes in the musculoskeletal system and inspiratory muscle weakness, which may be restored by inspiratory muscle training, thus increasing respiratory muscle strength and endurance, maximal oxygen uptake (VO2), functional capacity, respiratory responses to exercise, and quality of life. Yoga therapies have been shown to improve quality of life, inflammatory markers, and peak VO2 mostly in HF patients with a reduced ejection fraction. However, the effect of different yoga breathing techniques in patients showing HF with a preserved ejection fraction (HFpEF) remain to be assessed. METHODS/DESIGN: A PROBE (prospective randomized open blinded end-point) parallel-group trial will be conducted at two specialized HF clinics. Adult patients previously diagnosed with HFpEF will be included. After signing informed consent and performing a pre-test intervention, patients will be randomized into three groups and provided with either (1) active yoga breathing techniques; (2) passive yoga breathing techniques (pranayama); or and (3) control (standard pharmacological treatment). Follow-up will last 8 weeks (16 sessions). The post-intervention tests will be performed at the end of the intervention period for analysis of outcomes. Interventions will occur continuously according to patients' enrollment. The main outcome is respiratory muscular resistance. A total of 33 enrolled patients are expected. The present protocol followed the SPIRIT guidelines and fulfilled the SPIRIT checklist. DISCUSSION: This trial is probably the first to assess the effects of a non-pharmacological intervention, namely yoga and specific breathing techniques, to improve cardiorespiratory function, autonomic system, and quality of life in patients with HFpEF. TRIAL REGISTRATION: REBEC Identifier: RBR-64mbnx (August 19, 2012). Clinical Trials Register: NCT03028168 . Registered on 16 January 2017).

Disrupted day-night pattern of cardiovascular death in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) patients who suffer sudden cardiac death die predominantly during the night. We aimed to investigate whether all cardiovascular-related deaths display the same night-time peak as sudden cardiac death. METHODS: Data from a large cohort of adults who underwent full-night polysomnography between 1985 and 2015 in a university-affiliated sleep clinic were analyzed. Time and cause of death of these patients and of persons from the general population were identified in death certificates from the State Health Secretariat. The day-night pattern of cardiovascular death was compared among groups of non-OSA, OSA (apnea-hypopnea index, AHI ≥5), CPAP users, and persons from the general population. RESULTS: Among 619 certificates, 160 cardiovascular-related deaths were identified. The time of death of the 142 persons with OSA was uniformly distributed over 24 h, with neither an identifiable peak nor a circadian pattern (Rayleigh test; P = 0.8); the same flat distribution was seen in those with purported CPAP use (n = 49). Non-OSA individuals presented a morning peak and a night nadir of deaths, clearer when analyzed in eight-hour intervals. The same pattern was observed in 92 836 certificates from the State general population, with cardiovascular deaths showing the expected morning peak, night nadir, and a significant circadian pattern (Rayleigh test; P < 0.001). CONCLUSIONS: In OSA patients, the distribution of cardiovascular-related deaths throughout the 24-h period is virtually flat, in contrast with the described nighttime peak of sudden cardiac death. OSA-related phenomena during nighttime might be blunting the mechanisms, arrhythmic or not, behind the morning peak of cardiovascular-related deaths.

Cardiac autonomic modulation in polycystic ovary syndrome: does the phenotype matter?

OBJECTIVE: To assess whether heart rate variability (HRV) at rest and during sympathetic stimulation is disturbed in patients with different polycystic ovary syndrome (PCOS) phenotypes in comparison to healthy controls. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): Thirty women with classic, anovulatory PCOS, 16 women with ovulatory PCOS, and 23 age-paired women with regular and proven ovulatory cycles. INTERVENTION(S): Anthropometric and hormonal evaluation and analysis of HRV (time and frequency domain HRV indices) at rest and after a mental stress test. MAIN OUTCOME MEASURE(S): Difference between HRV components during rest and stress. RESULT(S): Mean age was 22.80 ± 5.80 years in patients with classic PCOS, 19.81 ± 6.43 years in ovulatory PCOS, and 22.65 ± 5.89 years in controls. During mental stress, patients with classic PCOS showed lower HRV response when compared with the control group, even after adjustment for body mass index (BMI) and age. When patients with classic and ovulatory PCOS were considered together, total T levels were inversely associated with the low frequency component, low frequency/high frequency ratio, and the difference between high frequency response at rest and after the stress test. CONCLUSION(S): Young patients with the classic PCOS phenotype have an impaired autonomic modulation in response to sympathetic stimulation that is typical of considerably older women, or of advanced age.

Inspiratory muscle training in type 2 diabetes with inspiratory muscle weakness.

PURPOSE: Patients with type 2 diabetes mellitus may present weakness of the inspiratory muscles. We tested the hypothesis that inspiratory muscle training (IMT) could improve inspiratory muscle strength, pulmonary function, functional capacity, and autonomic modulation in patients with type 2 diabetes and weakness of the inspiratory muscles. METHODS: Maximal inspiratory muscle pressure (PImax) was evaluated in a sample of 148 patients with type 2 diabetes. Of these, 25 patients with PImax<70% of predicted were randomized to an 8-wk program of IMT (n=12) or placebo-IMT (n=13). PImax, inspiratory muscle endurance time, pulmonary function, peak oxygen uptake, and HR variability were evaluated before and after intervention. RESULTS: The prevalence of inspiratory muscle weakness was 29%. IMT significantly increased the PImax (118%) and the inspiratory muscle endurance time (495%), with no changes in pulmonary function, functional capacity, or autonomic modulation. There were no significant changes with placebo-IMT. CONCLUSIONS: Patients with type 2 diabetes may frequently present inspiratory muscle weakness. In these patients, IMT improves inspiratory muscle function with no consequences in functional capacity or autonomic modulation.