Arterial Stiffness and Cardiorespiratory Fitness Impairment in the Community.

Background During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community-dwelling individuals. Methods and Results Arterial tonometry and maximum effort cardiopulmonary exercise testing were performed on Framingham Heart Study participants (N=2898, age 54±9 years, 53% women, body mass index 28.

Blood-Based Fingerprint of Cardiorespiratory Fitness and Long-Term Health Outcomes in Young Adulthood.

Background Cardiorespiratory fitness is a powerful predictor of health outcomes that is currently underused in primary prevention, especially in young adults. We sought to develop a blood-based biomarker of cardiorespiratory fitness that is easily translatable across populations. Methods and Results Maximal effort cardiopulmonary exercise testing for quantification of cardiorespiratory fitness (by peak oxygen uptake) and profiling of >200 metabolites at rest were performed in the FHS (Framingham Heart Study; 2016-2019).

Physical activity and fitness in the community: the Framingham Heart Study.

Aims: While greater physical activity (PA) is associated with improved health outcomes, the direct links between distinct components of PA, their changes over time, and cardiorespiratory fitness are incompletely understood.

Methods And Results: Maximum effort cardiopulmonary exercise testing (CPET) and objective PA measures [sedentary time (SED), steps/day, and moderate-vigorous PA (MVPA)] via accelerometers worn for 1 week concurrent with CPET and 7.8 years prior were obtained in 2070 Framingham Heart Study participants [age 54 ± 9 years, 51% women, SED 810 ± 83 min/day, steps/day 7737 ± 3520, MVPA 22.

Feasibility, Methodology, and Interpretation of Broad-Scale Assessment of Cardiorespiratory Fitness in a Large Community-Based Sample.

Cardiorespiratory fitness (CRF) is intricately related to health status. The optimal approach for CRF quantification is through assessment of peak oxygen uptake (VO), but such measurements have been largely confined to small referral populations. Here we describe protocols and methodological considerations for peak VO assessment and determination of volitional effort in a large community-based sample.

Metabolic Architecture of Acute Exercise Response in Middle-Aged Adults in the Community.

Background: Whereas regular exercise is associated with lower risk of cardiovascular disease and mortality, mechanisms of exercise-mediated health benefits remain less clear. We used metabolite profiling before and after acute exercise to delineate the metabolic architecture of exercise response patterns in humans.

Methods: Cardiopulmonary exercise testing and metabolite profiling was performed on Framingham Heart Study participants (age 53±8 years, 63% women) with blood drawn at rest (n=471) and at peak exercise (n=411).

An expanded repertoire of intensity-dependent exercise-responsive plasma proteins tied to loci of human disease risk.

Routine endurance exercise confers numerous health benefits, and high intensity exercise may accelerate and magnify many of these benefits. To date, explanatory molecular mechanisms and the influence of exercise intensity remain poorly understood. Circulating factors are hypothesized to transduce some of the systemic effects of exercise.

Impaired Exercise Tolerance in Heart Failure With Preserved Ejection Fraction: Quantification of Multiorgan System Reserve Capacity.

Exercise intolerance is a principal feature of heart failure with preserved ejection fraction (HFpEF), whether or not there is evidence of congestion at rest. The degree of functional limitation observed in HFpEF is comparable to patients with advanced heart failure and reduced ejection fraction. Exercise intolerance in HFpEF is characterized by impairments in the physiological reserve capacity of multiple organ systems, but the relative cardiac and extracardiac deficits vary among individuals.

Clinical and Hemodynamic Associations and Prognostic Implications of Ventilatory Efficiency in Patients With Preserved Left Ventricular Systolic Function.

Background: Ventilatory efficiency (minute ventilation required to eliminate carbon dioxide, VE/VCO2) during exercise potently predicts outcomes in advanced heart failure with reduced ejection fraction, but its prognostic significance for at-risk individuals with preserved left ventricular systolic function is unclear. We aimed to characterize mechanistic determinants and prognostic implications of VE/VCO2 in a single-center dyspneic referral cohort (MGH-ExS [Massachusetts General Hospital Exercise Study]) and in a large sample of community-dwelling participants in the FHS (Framingham Heart Study).

Methods: Maximum incremental cardiopulmonary exercise tests were performed.

Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Diagnosing and Ranking Its Causes Using Personalized O Pathway Analysis.

Background: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with a pressing shortage of therapies. Exercise intolerance is a cardinal symptom of HFpEF, yet its pathophysiology remains uncertain.

Methods: We investigated the mechanism of exercise intolerance in 134 patients referred for cardiopulmonary exercise testing: 79 with HFpEF and 55 controls.

Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction.

Background: Exercise capacity as measured by peak oxygen uptake (Vo2) is similarly impaired in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). However, characterization of how each component of Vo2 changes in response to incremental exercise in HFpEF versus HFrEF has not been previously defined. We hypothesized that abnormally low peripheral o2 extraction (arterio-mixed venous o2 content difference, [C(a-v)o2]) during exercise significantly contributes to impaired exercise capacity in HFpEF.

Causes of exercise intolerance in heart failure with preserved ejection fraction: searching for consensus.

Exercise intolerance is one of the cardinal symptoms of heart failure with preserved ejection fraction (HFpEF). We review its mechanistic basis using evidence from exercise studies. One barrier to a consensus understanding of the pathophysiology is heterogeneity of the patient population.

The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance.

Objective: We identified lipocalin 2 (Lcn2) as a gene induced by dexamethasone and tumor necrosis factor-alpha in cultured adipocytes. The purpose of this study was to determine how expression of Lcn2 is regulated in fat cells and to ascertain whether Lcn2 could be involved in metabolic dysregulation associated with obesity.

Research Design And Methods: We examined Lcn2 expression in murine tissues and in 3T3-L1 adipocytes in the presence and absence of various stimuli.