IMPORTANCE: Guidelines recommend 150 minutes or more of moderate to vigorous physical activity (MVPA) per week for overall health benefit, but the relative effects of concentrated vs more evenly ...distributed activity are unclear. OBJECTIVE: To examine associations between an accelerometer-derived “weekend warrior” pattern (ie, most MVPA achieved over 1-2 days) vs MVPA spread more evenly with risk of incident cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of UK Biobank cohort study participants providing a full week of accelerometer-based physical activity data between June 8, 2013, and December 30, 2015. EXPOSURES: Three MVPA patterns were compared: active weekend warrior (active WW, ≥150 minutes with ≥50% of total MVPA achieved in 1-2 days), active regular (≥150 minutes and not meeting active WW status), and inactive (<150 minutes). The same patterns were assessed using the sample median threshold of 230.4 minutes or more of MVPA per week. MAIN OUTCOMES AND MEASURES: Associations between activity pattern and incident atrial fibrillation, myocardial infarction, heart failure, and stroke were assessed using Cox proportional hazards regression, adjusted for age, sex, racial and ethnic background, tobacco use, alcohol intake, Townsend Deprivation Index, employment status, self-reported health, and diet quality. RESULTS: A total of 89 573 individuals (mean SD age, 62 7.8 years; 56% women) who underwent accelerometry were included. When stratified at the threshold of 150 minutes or more of MVPA per week, a total of 37 872 were in the active WW group (42.2%), 21 473 were in the active regular group (24.0%), and 30 228 were in the inactive group (33.7%). In multivariable-adjusted models, both activity patterns were associated with similarly lower risks of incident atrial fibrillation (active WW: hazard ratio HR, 0.78 95% CI, 0.74-0.83; active regular: 0.81 95% CI, 0.74-0.88; inactive: HR, 1.00 95% CI, 0.94-1.07), myocardial infarction (active WW: 0.73 95% CI, 0.67-0.80; active regular: 0.65 95% CI, 0.57-0.74; and inactive: 1.00 95% CI, 0.91-1.10), heart failure (active WW: 0.62 95% CI, 0.56-0.68; active regular: 0.64 95% CI, 0.56-0.73; and inactive: 1.00 95% CI, 0.92-1.09), and stroke (active WW: 0.79 95% CI, 0.71-0.88; active regular: 0.83 95% CI, 0.72-0.97; and inactive: 1.00 95% CI, 0.90-1.11). Findings were consistent at the median threshold of 230.4 minutes or more of MVPA per week, although associations with stroke were no longer significant (active WW: 0.89 95% CI, 0.79-1.02; active regular: 0.87 95% CI, 0.74-1.02; and inactive: 1.00 95% CI, 0.90-1.11). CONCLUSIONS AND RELEVANCE: Physical activity concentrated within 1 to 2 days was associated with similarly lower risk of cardiovascular outcomes to more evenly distributed activity.
Aortic valve area (AVA) ≤1.0 cm2 is a defining characteristic of severe aortic stenosis (AS). AVA can be underestimated at low transvalvular flow rate. Yet, the impact of flow rate on prognostic ...value of AVA ≤1.0 cm2 is unknown and is not incorporated into AS assessment.
This study aimed to evaluate the effect of flow rate on prognostic value of AVA in AS.
In total, 1,131 patients with moderate or severe AS and complete clinical follow-up were included as part of a longitudinal database. The effect of flow rate (ratio of stroke volume to ejection time) on prognostic value of AVA ≤1.0 cm2 for time to death was evaluated, adjusting for confounders. Sensitivity analysis was performed to identify the optimal cutoff for prognostic threshold of AVA. The findings were validated in a separate external longitudinal cohort of 939 patients.
Flow rate had a significant effect on prognostic value of AVA. AVA ≤1.0 cm2 was not prognostic for mortality (p = 0.15) if AVA was measured at flow rates below median (≤242 ml/s). In contrast, AVA ≤1.0 cm2 was highly prognostic for mortality (p = 0.003) if AVA was measured at flow rates above median (>242 ml/s). Findings were irrespective of multivariable adjustment for age, sex, and surgical/transcatheter aortic valve replacement (as time-dependent covariates); comorbidities; medications; and echocardiographic features. AVA ≤1.0 cm2 was also not an independent predictor of mortality below median flow rate in the validation cohort. The optimal flow rate cutoff for prognostic threshold was 210 ml/s.
Transvalvular flow rate determines prognostic value of AVA in AS. AVA measured at low flow rate is not a good prognostic marker and therefore not a good diagnostic marker for truly severe AS. Flow rate assessment should be incorporated into clinical diagnosis, classification, and prognosis of AS.
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Mitral annular calcification (MAC) is a common clinical finding and is associated with adverse clinical outcomes, but the clinical impact of MAC-related mitral valve (MV) dysfunction remains ...underappreciated. Patients with MAC frequently have stenotic, regurgitant, or mixed valvular disease, and this valvular dysfunction is increasingly recognized to be independently associated with worse prognosis. MAC-related MV dysfunction is a distinct pathophysiologic entity, and importantly much of the diagnostic and therapeutic paradigm from published rheumatic MV disease research cannot be applied in this context, leaving important gaps in our knowledge. This review summarizes the current epidemiology, pathophysiology, diagnosis, and classification of MAC-related MV dysfunction and proposes both an integrative definition and an overarching approach to this important and increasingly recognized clinical condition.
Purpose of review
Myocardial adaptation to athletics and exercise training is a well-described process that has garnered much interest over the past decades. By contrast, our understanding of how the ...vascular system adapts in the trained athlete remains limited. The goal of this review is to provide a comprehensive overview of the impact of exercise on structure and function of the extra-cardiac vascular system.
Recent findings
While structural changes in the size of the aorta are rare in young athletes, emerging data suggest that long-term athletic participation may be a risk factor for aortic dilation in middle-age and beyond. In addition, new findings show that even modest amounts of athletic training such as participation in an individual’s first marathon can have important salutary effects on vascular health.
Summary
Vascular adaptations represent an important part of the athletic phenotype and likely play an important role in the overall cardiovascular health of the trained athlete.
Oxygen uptake (V̇o
) at exercise onset is determined in part by acceleration of pulmonary blood flow (Formula: see text). Impairments in the Formula: see text response can decrease exercise ...tolerance. Prior research has shown that voluntary respiratory maneuvers can augment venous return, but the corollary impacts on cardiac function, Formula: see text and early-exercise V̇o
remain uncertain. We examined
) the cardiovascular effects of three distinct respiratory maneuvers (abdominal, AB; rib cage, RC; and deep breathing, DB) under resting conditions in healthy subjects (
,
= 13), and
) the impact of pre-exercise DB on pulmonary O
transfer during initiation of moderate-intensity exercise (
,
= 8). In
, echocardiographic analysis showed increased right ventricular (RV) cardiac output and left ventricular (LV) cardiac output (RVCO and LVCO, respectively), following AB (by +23 ± 13 and +18 ± 15%, respectively,
< 0.05), RC (+23 ± 16; +14 ± 15%,
< 0.05), and DB (+27 ± 21; +23 ± 14%,
< 0.05). In
, DB performed for 12 breaths produced a pre-exercise increase in V̇o
(+801 ± 254 mL·min
over ∼6 s), presumably from increased Formula: see text, followed by a reduction in pulmonary O
transfer during early phase exercise (first 20 s) compared with the control condition (149 ± 51 vs. 233 ± 65 mL,
< 0.05). We conclude that
) respiratory maneuvers enhance RVCO and LVCO in healthy subjects under resting conditions,
) AB, RC, and DB have similar effects on RVCO and LVCO, and
) DB can increase Formula: see text before exercise onset. These findings suggest that pre-exercise respiratory maneuvers may represent a promising strategy to prime V̇o
kinetics and thereby to potentially improve exercise tolerance in patients with impaired cardiac function.
We demonstrate that different breathing maneuvers can augment both right and left-sided cardiac output in healthy subjects. These maneuvers, when performed immediately before exercise, result in a pre-exercise "cardiodynamic" increase in oxygen uptake (V̇o
) associated with a subsequent reduction in the "cardiodynamic" V̇o
normally seen during early exercise. We conclude that pre-exercise breathing maneuvers are a plausible tool worthy of additional study to prime V̇o
kinetics and improve exercise tolerance in patients with cardiovascular disease.
Many aspects of sleep are heritable, but only a few sleep-regulating genes have been reported. Here, we leverage mouse models to identify and confirm a previously unreported gene affecting sleep ...duration—dihydropyrimidine dehydrogenase (Dpyd). Using activity patterns to quantify sleep in 325 Diversity Outbred (DO) mice—a population with high genetic and phenotypic heterogeneity—a linkage peak for total sleep in the active lights off period was identified on chromosome 3 (LOD score = 7.14). Mice with the PWK/PhJ ancestral haplotype at this location demonstrated markedly reduced sleep. Among the genes within the linkage region, available RNA sequencing data in an independent sample of DO mice supported a highly significant expression quantitative trait locus for Dpyd, wherein reduced expression was associated with the PWK/PhJ allele. Validation studies were performed using activity monitoring and EEG/EMG recording in Collaborative Cross mouse strains with and without the PWK/PhJ haplotype at this location, as well as EEG and EMG recording of sleep and wake in Dpyd knockout mice and wild-type littermate controls. Mice lacking Dpyd had 78.4 min less sleep during the lights-off period than wild-type mice (p = 0.007; Cohen’s d = −0.94). There was no difference in other measured behaviors in knockout mice, including assays evaluating cognitive-, social-, and affective-disorder-related behaviors. Dpyd encodes the rate-limiting enzyme in the metabolic pathway that catabolizes uracil and thymidine to β-alanine, an inhibitory neurotransmitter. Thus, data support β-alanine as a neurotransmitter that promotes sleep in mice.
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•Dihydropyrimidine dehydrogenase (Dpyd) affects sleep in Diversity Outbred mice•Knockout of Dpyd resulted in 78.4 min less sleep in lights-off period•No differences in other measured behaviors with knockout of Dpyd•Results support β-alanine as a neurotransmitter that promotes sleep
Many aspects of sleep are heritable, but few genes have been reported. Keenan et al. combine discovery in Diversity Outbred mice with validation in both Collaborative Cross and knockout mice to implicate dihydropyrimidine dehydrogenase (Dpyd) as a gene affecting sleep. This, in turn, supports β-alanine as a sleep-promoting neurotransmitter in mice.
•We measured heart and lung function as well as blood pressure in men and women with heart failure who underwent specialized bicycle-exercise stress testing.•Women with heart failure had stiffer ...blood vessels than men.•Stiffer blood vessels were associated with greater difficulty exercising, especially in women with heart failure.
Mechanisms underlying sex differences in heart failure with preserved ejection fraction (HFpEF) are poorly understood. We sought to examine sex differences in measures of arterial stiffness and the association of arterial stiffness measures with left ventricular hemodynamic responses to exercise in men and women.
We studied 83 men (mean age 62 years) and 107 women (mean age 59 years) with HFpEF who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial stiffness measurement (augmentation pressure AP, augmentation index AIx, and aortic pulse pressure AoPP). Sex differences were compared using multivariable linear regression. We examined the association of arterial stiffness with abnormal left ventricular diastolic response to exercise, defined as a rise in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO) ≥ 2 mmHg/L/min by using logistic regression models.
Women with HFpEF had increased arterial stiffness compared with men. AP was nearly 10 mmHg higher, and AIx was more than 10% higher in women compared with men (P < 0.0001 for both). Arterial stiffness measures were associated with a greater pulmonary capillary wedge pressure response to exercise, particularly among women. A 1-standard deviation higher AP was associated with > 3-fold increased odds of abnormal diastolic exercise response (AP: OR 3.16, 95% CI 1.34–7.42; P = 0.008 women vs OR 2.07, 95% CI 0.95–5.49; P = 0.15 men) with similar findings for AIx and AoPP.
Arterial stiffness measures are significantly higher in women with HFpEF than in men and are associated with abnormally steep increases in pulmonary capillary wedge pressure with exercise, particularly in women. Arterial stiffness may preferentially contribute to abnormal diastolic function during exercise in women with HFpEF compared with men.
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