Exercise to Prevent Accelerated Vascular Aging in People Living With HIV.

Given advances in antiretroviral therapy, the mortality rate for HIV infection has dropped considerably over recent decades. However, people living with HIV (PLWH) experience longer life spans coupled with persistent immune activation despite viral suppression and potential toxicity from long-term antiretroviral therapy use. Consequently, PLWH face a cardiovascular disease (CVD) risk more than twice that of the general population, making it the leading cause of death among this group. Here, we briefly review the epidemiology of CVD in PLWH highlighting disparities at the intersections of sex and gender, age, race/ethnicity, and the contributions of social determinants of health and psychosocial stress to increased CVD risk among individuals with marginalized identities. We then overview the pathophysiology of HIV and discuss the primary factors implicated as contributors to CVD risk among PLWH on antiretroviral therapy. Subsequently, we highlight the functional evidence of premature vascular dysfunction as an early pathophysiological determinant of CVD risk among PLWH, discuss several mechanisms underlying premature vascular dysfunction in PLWH, and synthesize current research on the pathophysiological mechanisms underlying accelerated vascular aging in PLWH, focusing on immune activation, chronic inflammation, and oxidative stress. We consider understudied aspects such as HIV-related changes to the gut microbiome and psychosocial stress, which may serve as mechanisms through which exercise can abrogate accelerated vascular aging. Emphasizing the significance of exercise, we review various modalities and their impacts on vascular health, proposing a holistic approach to managing CVD risks in PLWH. The discussion extends to critical future study areas related to vascular aging, CVD, and the efficacy of exercise interventions, with a call for more inclusive research that considers the diversity of the PLWH population.

The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults.

Denervated myofibers and senescent cells are hallmarks of skeletal muscle aging. However, sparse research has examined how resistance training affects these outcomes. We investigated the effects of unilateral leg extensor resistance training (2 days/week for 8 weeks) on denervated myofibers, senescent cells, and associated protein markers in apparently healthy middle-aged participants (MA, 55 ± 8 years old, 17 females, 9 males). We obtained dual-leg vastus lateralis (VL) muscle cross-sectional area (mCSA), VL biopsies, and strength assessments before and after training. Fiber cross-sectional area (fCSA), satellite cells (Pax7+), denervated myofibers (NCAM+), senescent cells (p16+ or p21+), proteins associated with denervation and senescence, and senescence-associated secretory phenotype (SASP) proteins were analyzed from biopsy specimens. Leg extensor peak torque increased after training (p < .001), while VL mCSA trended upward (interaction p = .082). No significant changes were observed for Type I/II fCSAs, NCAM+ myofibers, or senescent (p16+ or p21+) cells, albeit satellite cells increased after training (p = .037). While >90% satellite cells were not p16+ or p21+, most p16+ and p21+ cells were Pax7+ (>90% on average). Training altered 13 out of 46 proteins related to muscle-nerve communication (all upregulated, p < .05) and 10 out of 19 proteins related to cellular senescence (9 upregulated, p < .05). Only 1 out of 17 SASP protein increased with training (IGFBP-3, p = .031). In conclusion, resistance training upregulates proteins associated with muscle-nerve communication in MA participants but does not alter NCAM+ myofibers. Moreover, while training increased senescence-related proteins, this coincided with an increase in satellite cells but not alterations in senescent cell content or SASP proteins. These latter findings suggest shorter term resistance training is an unlikely inducer of cellular senescence in apparently healthy middle-aged participants. However, similar study designs are needed in older and diseased populations before definitive conclusions can be drawn.

Making the case for resistance training in improving vascular function and skeletal muscle capillarization.

Through decades of empirical data, it has become evident that resistance training (RT) can improve strength/power and skeletal muscle hypertrophy. Yet, until recently, vascular outcomes have historically been underemphasized in RT studies, which is underscored by several exercise-related reviews supporting the benefits of endurance training on vascular measures. Several lines of evidence suggest large artery diameter and blood flow velocity increase after a single bout of resistance exercise, and these events are mediated by vasoactive substances released from endothelial cells and myofibers (e.g., nitric oxide). Weeks to months of RT can also improve basal limb blood flow and arterial diameter while lowering blood pressure. Although several older investigations suggested RT reduces skeletal muscle capillary density, this is likely due to most of these studies being cross-sectional in nature. Critically, newer evidence from longitudinal studies contradicts these findings, and a growing body of mechanistic rodent and human data suggest skeletal muscle capillarity is related to mechanical overload-induced skeletal muscle hypertrophy. In this review, we will discuss methods used by our laboratories and others to assess large artery size/function and skeletal muscle capillary characteristics. Next, we will discuss data by our groups and others examining large artery and capillary responses to a single bout of resistance exercise and chronic RT paradigms. Finally, we will discuss RT-induced mechanisms associated with acute and chronic vascular outcomes.

Acute high-dose MitoQ does not increase urinary kidney injury markers in healthy adults: a randomized crossover trial.

Several human studies have used the mitochondrial antioxidant MitoQ. Recent in vitro data indicating that MitoQ may induce nephrotoxicity caused concern regarding the safety of MitoQ on the kidneys, but the doses were supraphysiological. Therefore, we sought to determine whether acute MitoQ elicits changes in urinary biomarkers associated with tubular injury in healthy adults with our hypothesis being there would be no changes. Using a randomized crossover design, 32 healthy adults (16 females and 16 males, 29 ± 11 yr old) consumed MitoQ (100-160 mg based on body mass) or placebo capsules. We obtained serum samples and a 4- to 6-h postcapsule consumption urine sample. We assessed creatinine clearance and urine kidney injury biomarkers including the chitinase 3-like-1 gene product YKL-40, kidney-injury marker-1, monocyte chemoattractant protein-1, epidermal growth factor, neutrophil gelatinase-associated lipocalin, interleukin-18, and uromodulin using multiplex assays. We used t tests, Wilcoxon tests, and Hotelling's T2 to assess global differences in urinary kidney injury markers between conditions. Acute MitoQ supplementation did not influence urine flow rate (P = 0.086, rrb = 0.39), creatinine clearance (P = 0.085, rrb = 0.42), or urinary kidney injury markers (T22,8 = 30.6, P = 0.121, univariate ps > 0.064). Using exploratory univariate analysis, MitoQ did not alter individual injury markers compared with placebo (e.g., placebo vs. MitoQ: YKL-40, 507 ± 241 vs. 442 ± 236 pg/min, P = 0.241; kidney injury molecule-1, 84.1 ± 43.2 vs. 76.2 ± 51.2 pg/min, P = 0.890; and neutrophil gelatinase-associated lipocalin, 10.8 ± 10.1 vs. 9.83 ± 8.06 ng/min, P = 0.609). In conclusion, although longer-term surveillance and data are needed in clinical populations, our findings suggest that acute high-dose MitoQ had no effect on urinary kidney injury markers in healthy adults.NEW & NOTEWORTHY We found acute high-dose mitochondria-targeted antioxidant (MitoQ) supplementation was not nephrotoxic and had no effect on markers of acute kidney injury in healthy adults. These findings can help bolster further confidence in the safety of MitoQ, particularly for future investigations seeking to examine the role of mitochondrial oxidative stress, via acute MitoQ supplementation, on various physiological outcomes.

Guidelines on the use of sex and gender in cardiovascular research.

In cardiovascular research, sex and gender have not typically been considered in research design and reporting until recently. This has resulted in clinical research findings from which not only all women, but also gender-diverse individuals have been excluded. The resulting dearth of data has led to a lack of sex- and gender-specific clinical guidelines and raises serious questions about evidence-based care. Basic research has also excluded considerations of sex. Including sex and/or gender as research variables not only has the potential to improve the health of society overall now, but it also provides a foundation of knowledge on which to build future advances. The goal of this guidelines article is to provide advice on best practices to include sex and gender considerations in study design, as well as data collection, analysis, and interpretation to optimally establish rigor and reproducibility needed to inform clinical decision-making and improve outcomes. In cardiovascular physiology, incorporating sex and gender is a necessary component when optimally designing and executing research plans. The guidelines serve as the first guidance on how to include sex and gender in cardiovascular research. We provide here a beginning path toward achieving this goal and improve the ability of the research community to interpret results through a sex and gender lens to enable comparison across studies and laboratories, resulting in better health for all.

Salty Subjects: Unpacking Racial Differences in Salt-Sensitive Hypertension.

PURPOSE OF REVIEW: To review underlying mechanisms and environmental factors that may influence racial disparities in the development of salt-sensitive blood pressure. RECENT FINDINGS: Our group and others have observed racial differences in diet and hydration, which may influence salt sensitivity. Dietary salt elicits negative alterations to the gut microbiota and immune system, which may increase hypertension risk, but little is known regarding potential racial differences in these physiological responses. Antioxidant supplementation and exercise offset vascular dysfunction following dietary salt, including in Black adults. Furthermore, recent work proposes the role of racial differences in exposure to social determinants of health, and differences in health behaviors that may influence risk of salt sensitivity. Physiological and environmental factors contribute to the mechanisms that manifest in racial differences in salt-sensitive blood pressure. Using this information, additional work is needed to develop strategies that can attenuate racial disparities in salt-sensitive blood pressure.

Adjusting for muscle strength and body size attenuates sex differences in the exercise pressor reflex in young adults.

Females typically exhibit lower blood pressure (BP) during exercise than males. However, recent findings indicate that adjusting for maximal strength attenuates sex differences in BP during isometric handgrip (HG) exercise and postexercise ischemia (PEI; metaboreflex isolation). In addition, body size is associated with HG strength but its contribution to sex differences in exercising BP is less appreciated. Therefore, the purpose of this study was to determine whether adjusting for strength and body size would attenuate sex differences in BP during HG and PEI. We obtained beat-to-beat BP in 110 participants (36 females, 74 males) who completed 2 min of isometric HG exercise at 40% of their maximal voluntary contraction followed by 3 min of PEI. In a subset (11 females, 17 males), we collected muscle sympathetic nerve activity (MSNA). Statistical analyses included independent t tests and mixed models (sex × time) with covariate adjustment for 40% HG force, height2, and body surface area. Females exhibited a lower absolute 40% HG force than male participants (Ps < 0.001). Females exhibited lower Δsystolic, Δdiastolic, and Δmean BPs during HG and PEI than males (e.g., PEI, Δsystolic BP, 15 ± 11 vs. 23 ± 14 mmHg; P = 0.004). After covariate adjustment, sex differences in BP responses were attenuated. There were no sex differences in MSNA. In a smaller strength-matched cohort, there was no sex × time interactions for BP responses (e.g., PEI systolic BP, P = 0.539; diastolic BP, P = 0.758). Our data indicate that sex differences in exercising BP responses are attenuated after adjusting for muscle strength and body size.NEW & NOTEWORTHY When compared with young males, females typically exhibit lower blood pressure (BP) during exercise. Adjusting for maximal strength attenuates sex differences in BP during isometric handgrip (HG) exercise and postexercise ischemia (PEI), but the contribution of body size is unknown. Novel findings include adjustments for muscle strength and body size attenuate sex differences in BP reactivity during exercise and PEI, and sex differences in body size contribute to HG strength differences.

Interplay of Race and Neighborhood Deprivation on Ambulatory Blood Pressure in Young Adults.

Background: Ambulatory blood pressure (BP) monitoring measures nighttime BP and BP dipping, which are superior to in-clinic BP for predicting cardiovascular disease (CVD), the leading cause of death in America. Compared with other racial/ethnic groups, Black Americans exhibit elevated nighttime BP and attenuated BP dipping, including in young adulthood. Social determinants of health contribute to disparities in CVD risk, but the contribution of neighborhood deprivation on nighttime BP is unclear. Therefore, we examined associations between neighborhood deprivation with nighttime BP and BP dipping in young Black and White adults. Methods: We recruited 21 Black and 26 White participants (20 M/27 F, mean age: 21 years, body mass index: 25±4 kg/m2) for 24-hour ambulatory BP monitoring. We assessed nighttime BP and BP dipping (nighttime:daytime BP ratio). The area deprivation index (ADI) was used to measure neighborhood deprivation. Associations between ADI and ambulatory BP were examined. Results: Black participants exhibited higher nighttime diastolic BP compared with White participants (63±8 mmHg vs 58±7 mmHg, p=0.003), and attenuated BP dipping ratios for both systolic (0.92±0.06 vs 0.86±0.05, p=0.001) and diastolic BP (0.86±0.09 vs 0.78±0.08, p=0.007). Black participants experienced greater neighborhood deprivation compared with White participants (ADI scores: 110±8 vs 97±21, p<0.001), and ADI was associated with attenuated systolic BP dipping (ρ=0.342, p=0.019). Conclusions: Our findings suggest neighborhood deprivation may contribute to higher nighttime BP and attenuated BP dipping, which are prognostic of CVD, and more prevalent in Black adults. Targeted interventions to mitigate the effects of neighborhood deprivation may help to improve nighttime BP. Clinical Trial Registry: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04576338.

Gut check: Unveiling the influence of acute exercise on the gut microbiota.

The human gastrointestinal microbiota and its unique metabolites regulate a diverse array of physiological processes with substantial implications for human health and performance. Chronic exercise training positively modulates the gut microbiota and its metabolic output. The benefits of chronic exercise for the gut microbiota may be influenced by acute changes in microbial community structure and function that follow a single exercise bout (i.e., acute exercise). Thus, an improved understanding of changes in the gut microbiota that occur with acute exercise could aid in the development of evidence-based exercise training strategies to target the gut microbiota more effectively. In this review, we provide a comprehensive summary of the existing literature on the acute and very short-term (<3 weeks) exercise responses of the gut microbiota and faecal metabolites in humans. We conclude by highlighting gaps in the literature and providing recommendations for future research in this area. NEW FINDINGS: What is the topic of this review? The chronic benefits of exercise for the gut microbiota are likely influenced by acute changes in microbial community structure and function that follow a single exercise bout. This review provides a summary of the existing literature on acute exercise responses of the gut microbiota and its metabolic output in humans. What advances does it highlight? Acute aerobic exercise appears to have limited effects on diversity of the gut microbiota, variable effects on specific microbial taxa, and numerous effects on the metabolic activity of gut microbes with possible implications for host health and performance.

Cross-sectional analysis of racial differences in hydration and neighborhood deprivation in young adults.

BACKGROUND: Inadequate hydration is associated with cardiovascular and kidney disease morbidity and all-cause mortality. Compared with White individuals, Black individuals exhibit a higher prevalence of inadequate hydration, which may contribute to racial health disparities. However, the underlying reasons for these differences in hydration remain unclear. OBJECTIVE: This cross-sectional study aimed to investigate whether neighborhood deprivation contributes to racial differences in hydration status. METHODS: We assessed 24 Black and 30 White college students, measuring 24-hour urine osmolality, urine flow rate, urine specific gravity, and plasma copeptin concentration. Participants recorded their food and fluid intake for 3 d to assess total water intake from food and beverages. Neighborhood socioeconomic deprivation was measured using a tract-level Area Deprivation Index. RESULTS: Black participants exhibited higher urine osmolality (640 [314] compared with 440 [283] mOsm/kg H2O, respectively, P = 0.006) and lower urine flow rate (1.06 [0.65] compared with 1.71 [0.89] ml/min, respectively, P = 0.009) compared with White participants, indicating greater hypohydration among Black participants. Black participants reported lower total water intake from food and beverages than White participants (2.3 ± 0.7 compared with 3.5 ± 1.1 L/day, respectively, P < 0.01). Black participants exhibited higher copeptin than White participants (6.3 [3.1] compared with 4.5 [2.3] pmol/L, P = 0.046), and urine osmolality mediated 67% of the difference (P = 0.027). Black participants reported greater cumulative exposure to neighborhood deprivation during childhood (ages 0-18 y). Furthermore, neighborhood deprivation during childhood was associated with urine specific gravity (P = 0.031) and total water intake from food and beverages (P = 0.042) but did not mediate the racial differences in these measures. CONCLUSION: Our data suggest that compared with White young adults, Black young adults are hypohydrated and exhibit higher plasma copeptin concentration, and that greater neighborhood deprivation is associated with chronic underhydration irrespective of race. This trial was registered at clinicaltrials.gov as NCT04576338.

The damaging duo: Obesity and excess dietary salt contribute to hypertension and cardiovascular disease.

Hypertension is a primary risk factor for cardiovascular disease. Cardiovascular disease is the leading cause of death among adults worldwide. In this review, we focus on two of the most critical public health challenges that contribute to hypertension-obesity and excess dietary sodium from salt (i.e., sodium chloride). While the independent effects of these factors have been studied extensively, the interplay of obesity and excess salt overconsumption is not well understood. Here, we discuss both the independent and combined effects of excess obesity and dietary salt given their contributions to vascular dysfunction, autonomic cardiovascular dysregulation, kidney dysfunction, and insulin resistance. We discuss the role of ultra-processed foods-accounting for nearly 60% of energy intake in America-as a major contributor to both obesity and salt overconsumption. We highlight the influence of obesity on elevated blood pressure in the presence of a high-salt diet (i.e., salt sensitivity). Throughout the review, we highlight critical gaps in knowledge that should be filled to inform us of the prevention, management, treatment, and mitigation strategies for addressing these public health challenges.

Acute beetroot juice reduces blood pressure in young Black and White males but not females.

A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.

Short-term high-salt consumption does not influence resting or exercising heart rate variability but increases MCP-1 concentration in healthy young adults.

High salt consumption increases blood pressure (BP) and cardiovascular disease risk by altering autonomic function and increasing inflammation. However, it is unclear whether salt manipulation alters resting and exercising heart rate variability (HRV), a noninvasive measure of autonomic function, in healthy young adults. The purpose of this investigation was to determine whether short-term high-salt intake 1) alters HRV at rest, during exercise, or exercise recovery and 2) increases the circulating concentration of the inflammatory biomarker monocyte chemoattractant protein 1 (MCP-1). With the use of a randomized, placebo-controlled, crossover study, 20 participants (8 females; 24 ± 4 yr old, 110 ± 10/64 ± 8 mmHg) consumed salt (3,900 mg sodium) or placebo capsules for 10 days each separated by ≥2 wk. We assessed HRV during 10 min of baseline rest, 50 min of cycling (60% V̇o2peak), and recovery. We quantified HRV using the standard deviation of normal-to-normal RR intervals, the root mean square of successive differences (RMSSD), and additional time and frequency domain metrics of HRV. Plasma samples were collected to assess MCP-1 concentration. No main effect of high salt or condition × time interaction was observed for HRV metrics. However, acute exercise reduced HRV (e.g., RMSSD time: P < 0.001, condition: P = 0.877, interaction: P = 0.422). High salt elevated plasma MCP-1 (72.4 ± 12.5 vs. 78.14 ± 14.7 pg/mL; P = 0.010). Irrespective of condition, MCP-1 was moderately associated (P values < 0.05) with systolic (r = 0.32) and mean BP (r = 0.33). Short-term high-salt consumption does not affect HRV; however, it increases circulating MCP-1, which may influence BP in young adults.

Molecular predictors of resistance training outcomes in young untrained female adults.

We sought to determine if the myofibrillar protein synthetic (MyoPS) response to a naïve resistance exercise (RE) bout, or chronic changes in satellite cell number and muscle ribosome content, were associated with hypertrophic outcomes in females or differed in those who classified as higher (HR) or lower (LR) responders to resistance training (RT). Thirty-four untrained college-aged females (23.4 ± 3.4 kg/m2) completed a 10-wk RT protocol (twice weekly). Body composition and leg imaging assessments, a right leg vastus lateralis biopsy, and strength testing occurred before and following the intervention. A composite score, which included changes in whole body lean/soft tissue mass (LSTM), vastus lateralis (VL) muscle cross-sectional area (mCSA), midthigh mCSA, and deadlift strength, was used to delineate upper and lower HR (n = 8) and LR (n = 8) quartiles. In all participants, training significantly (P < 0.05) increased LSTM, VL mCSA, midthigh mCSA, deadlift strength, mean muscle fiber cross-sectional area, satellite cell abundance, and myonuclear number. Increases in LSTM (P < 0.001), VL mCSA (P < 0.001), midthigh mCSA (P < 0.001), and deadlift strength (P = 0.001) were greater in HR vs. LR. The first-bout 24-hour MyoPS response was similar between HR and LR (P = 0.367). While no significant responder × time interaction existed for muscle total RNA concentrations (i.e., ribosome content) (P = 0.888), satellite cell abundance increased in HR (P = 0.026) but not LR (P = 0.628). Pretraining LSTM (P = 0.010), VL mCSA (P = 0.028), and midthigh mCSA (P < 0.001) were also greater in HR vs. LR. Female participants with an enhanced satellite cell response to RT, and more muscle mass before RT, exhibited favorable resistance training adaptations.NEW & NOTEWORTHY This study continues to delineate muscle biology differences between lower and higher responders to resistance training and is unique in that a female population was interrogated. As has been reported in prior studies, increases in satellite cell numbers are related to positive responses to resistance training. Satellite cell responsivity, rather than changes in muscle ribosome content per milligrams of tissue, may be a more important factor in delineating resistance-training responses in women.

Habituation attenuates the sex-specific associations between ischemic pain, blood pressure, and arterial stiffness in young adults.

Cardiovascular reactivity (CVR) during physical stress is prognostic for incident cardiovascular disease. CVR is influenced by perceived pain. However, there is limited data on the effect of sex differences and repeated exposures to painful stimuli on CVR. We measured blood pressure (BP) and carotid-femoral pulse wave velocity (cf-PWV; an index of arterial stiffness) at rest, during isometric handgrip (HG) exercise at 30% of maximum voluntary contraction, and during postexercise circulatory occlusion (PECO) during two identical trials in 39 adults (20M/19F; 18-39 yr). We assessed participants' perceived pain using a visual analog scale after the first minute of each stimulus. We collected BP during minute 2 of each stimulus and cf-PWV during minute 3 of each stimulus. In male participants, we observed moderate associations (Ps ≤ 0.023) between perceived pain and changes in brachial diastolic (ρ = 0.620) and mean BP (ρ = 0.597); central diastolic, mean, and systolic BP (ρs = 0.519-0.654); and cf-PWV (ρ = 0.680) during PECO in trial 1, but not trial 2 (Ps ≥ 0.162). However, in female participants, there were no associations between pain and CVR indices during either trial (Ps ≥ 0.137). Irrespective of sex, reductions in perceived pain during trial 2 relative to trial 1 were weakly to moderately associated (Ps ≤ 0.038) with reductions in brachial diastolic (ρ = 0.346), mean (ρ = 0.379), and systolic BP (ρ = 0.333); central mean (ρ = 0.400) and systolic BP (ρ = 0.369); and cf-PWV (ρ = 0.526). These findings suggest that 1) there are sex differences in pain modulation of CVR in young adults and 2) habituation blunts pain and CVR during PECO, irrespective of sex.NEW & NOTEWORTHY We demonstrate sex differences in the association between pain perception and cardiovascular reactivity (CVR) during ischemic pain. We also demonstrate habituation to pain and reduced CVR during repeated exposure in a sex-independent manner. Accounting for sex differences and habituation may improve the prognostic utility of CVR.

The janus face of ketone bodies in hypertension.

Hypertension is the most important risk factor for the development of terminal cardiovascular diseases, such as heart failure, chronic kidney disease, and atherosclerosis. Lifestyle interventions to lower blood pressure are generally desirable prior to initiating pharmaceutical drug treatments, which may have undesirable side effects. Ketogenic interventions are popular but the scientific literature supporting their efficacy is specific to certain interventions and outcomes in animal models and patient populations. For example, although caloric restriction has its own inherent difficulties (e.g. it requires high levels of motivation and adherence is difficult), it has unequivocally been associated with lowering blood pressure in hypertensive patients. On the other hand, the antihypertensive efficacy of ketogenic diets is inconclusive, and this is surprising, given that these diets have been largely helpful in mitigating metabolic syndrome and promoting longevity. It is possible that side effects associated with ketogenic diets (e.g. dyslipidemia) aggravate the hypertensive phenotype. However, given the recent data from our group, and others, reporting that the most abundant ketone body, ß-hydroxybutyrate, can have positive effects on endothelial and vascular health, there is hope that ketone bodies can be harnessed as a therapeutic strategy to combat hypertension. Therefore, we conclude this review with a summary of the type and efficacy of ketone supplements. We propose that ketone supplements warrant investigation as low-dose antihypertensive therapy that decreases total peripheral resistance with minimal adverse side effects.

Sleep duration irregularity is associated with elevated blood pressure in young adults.

Sleep irregularity (i.e., highly variable sleep patterns) is an emerging risk factor for cardiometabolic disease. Though irregular sleep patterns are common among young adults, the cardiometabolic health (CMH) repercussions of sleep irregularity in this population are unclear. We examined associations between sleep duration and irregularity with measures of CMH in 44 (24 M/20 F, 23 ± 5y, BMI 26 ± 4 kg/m2, blood pressure (BP): 125/71 ± 14/9 mmHg) young adults. Participants wore actigraphy monitors for seven-days and sleep duration irregularity was operationalized as the standard deviation of nightly sleep duration (sleep SD). CMH variables of interest included brachial and aortic BP, arterial stiffness (cf-PWV), augmentation index (AIx75), and fasting blood glucose and lipids. Associations between sleep duration and sleep SD with CMH variables were assessed via correlations adjusted for sex and BMI. Sleep duration generally was not associated with CMH indices. However, sleep SD was associated with brachial systolic (r = 0.433, p = .027) and diastolic BP (r = 0.415, p = .035). Similarly, sleep duration SD was associated with aortic systolic BP (r = 0.447, p = .022). Our findings show that sleep irregularity, but not duration, is associated with higher brachial and central BP in young adults.Abbreviations: AIx75: augmentation index at a heart rate of 75 beats per minute; BP: blood pressure; CMH: cardiometabolic health; cf-PWV: carotid-femoral pulse wave velocity; DXA: dual x-ray absorptiometry; mg/dl: milligrams per deciliter; PWA: pulse wave analysis; PWV: pulse wave velocity; sleep duration SD: standard deviation of nightly sleep duration.

Neighborhood Socioeconomic Deprivation in Early Childhood Mediates Racial Disparities in Blood Pressure in a College Student Sample.

The influence of childhood contexts on adult blood pressure is an important yet understudied topic. Using a developmental perspective, this study examines the association between neighborhood socioeconomic disadvantage in early childhood (0-5 yrs), middle childhood (6-12 yrs) and adolescence (13-18 yrs) on subsequent blood pressure in young adulthood. Data were from 263 college students (52% Black; Mage = 19.21 years) and neighborhood socioeconomic disadvantage was measured using a tract-level Area Deprivation Index. Neighborhood disadvantage in early childhood was significantly associated with diastolic blood pressure and explained 22% of the race difference between Black and White adults. The findings are consistent with the notion that early childhood may be a sensitive period for the effects of neighborhood disadvantage on blood pressure.