Nutritional Aspects to Cardiovascular Diseases and Type 2 Diabetes Mellitus.

PURPOSE OF REVIEW: In this narrative review, we discuss the current evidence related to the role of dietary interventions to prevent and treat type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). We also propose alternative therapeutic strategies other than weight loss in this population, namely, improvements in cardiorespiratory fitness and its determinants. RECENT FINDINGS: While weight loss has been consistently associated with the prevention of T2DM and improvements in glycemic control in those with established diseases, its role in preventing and treating CVD is less clear. In fact, in this setting, improvements in diet quality have provided greater benefits, suggesting that this might represent an alternative, or an even more effective strategy than energy-restriction. Improvements in diet quality, with and without caloric restriction have been shown to improve CVD risk and to prevent the development of T2DM in individuals at risk; however, with regard to glycemic control in patients with T2DM, any dietary intervention resulting in significant weight loss may produce clinically meaningful benefits. Finally, dietary interventions with and without energy restriction that can improve cardiorespiratory fitness, even in absence of weight loss in patients with obesity, should be encouraged.

The effect of time of eating on cardiometabolic risk in primary and secondary prevention of cardiovascular disease.

Continuous energy restriction is currently considered the first-line dietary therapy for weight loss in individuals with obesity. Recently, interventions which alter the eating window and time of eating occasions have been explored as means to achieve weight loss and other cardiometabolic improvements such as a reduction in blood pressure, glycaemia, lipids and inflammation. It is unknown, however, whether these changes result from unintentional energy restriction or from other mechanisms such as the alignment of nutrient intake with the internal circadian clock. Even less is known regarding the safety and efficacy of these interventions in individuals with established chronic noncommunicable disease states, such as cardiovascular disease. This review examines the effects of interventions which alter both eating window and time of eating occasions on weight and other cardiometabolic risk factors in both healthy participants and those with established cardiovascular disease. We then summarise the state of existing knowledge and explore future directions of study.

Time of eating and mortality in U.S. adults with heart failure: Analyses of the National Health and Nutrition Examination Survey 2003-2018.

BACKGROUND AND AIMS: Promising associations have been demonstrated between delayed last eating occasion and cardiorespiratory fitness in adults with heart failure (HF), however, it is unknown if time of eating is associated with clinical endpoints such as mortality. This study aimed to examine associations between time of eating variables and all-cause and cardiovascular mortality in the National Health and Nutrition Examination Survey (NHANES). METHODS AND RESULTS: Participants self-disclosed HF diagnosis. Two dietary recalls were obtained and categorical variables were created based on mean time of first eating occasion (8:31 AM), last eating occasion (7:33 PM) and eating window (11.02 h). Mortality was obtained through linkage to the National Death Index. Covariate-adjusted Cox proportional hazard regression models were created examining the association between time of eating and mortality. Participants (n = 991) were 68 (95 % CI 67-69) years of age, 52.6 (95 % CI 49.0-56.3)% men and had a body mass index of 32.5 (95 % CI 31.8-33.2) kg/m2 with follow up time of 68.9 (95 % CI 64.8-72.9) person-months. When models were adjusted for time of eating variables and all other covariates, extending the eating window beyond 11.02 h was associated with decreased risk of cardiovascular (HR 0.36 [95 % CI 0.16-0.81]), but not all-cause mortality. Time of first and last eating occasions were not associated with mortality. CONCLUSIONS: In adults with HF, an extended eating window is associated with reduced risk for cardiovascular mortality. Randomized controlled trials should examine if extending the eating window can improve prognostic indicators such as cardiorespiratory fitness in this population.

Life's Essential 8: Optimizing Health in Older Adults.

The population worldwide is getting older as a result of advances in public health, medicine, and technology. Older individuals are living longer with a higher prevalence of subclinical and clinical cardiovascular disease (CVD). In 2010, the American Heart Association introduced a list of key prevention targets, known as "Life's Simple 7" to increase CVD-free survival, longevity, and quality of life. In 2022, sleep health was added to expand the recommendations to "Life's Essential 8" (eat better, be more active, stop smoking, get adequate sleep, manage weight, manage cholesterol, manage blood pressure, and manage diabetes). These prevention targets are intended to apply regardless of chronologic age. During this same time, the understanding of aging biology and goals of care for older adults further enhanced the relevance of prevention across the range of functions. From a biological perspective, aging is a complex cellular process characterized by genomic instability, telomere attrition, loss of proteostasis, inflammation, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These aging hallmarks are triggered by and enhanced by traditional CVD risk factors leading to geriatric syndromes (eg, frailty, sarcopenia, functional limitation, and cognitive impairment) which complicate efforts toward prevention. Therefore, we review Life's Essential 8 through the lens of aging biology, geroscience, and geriatric precepts to guide clinicians taking care of older adults.

Skeletal muscle quality, measured via phase angle, and cardiorespiratory fitness in patients with obesity and heart failure with preserved ejection fraction.

OBJECTIVES: Cardiorespiratory fitness (CRF) is influenced by body composition quantity and quality in heart failure with preserved ejection fraction (HFpEF) and obesity. Bioelectrical impedance analysis (BIA) provides a noninvasive quantitative and qualitative body composition assessment. The aim of this study was to determine the role of phase angle (PhA), a BIA-measure of skeletal muscle quality and body cell mass, on CRF in patients with obesity and HFpEF. METHODS: Fifty-nine consecutive outpatients with HFpEF underwent cardiopulmonary exercise testing to measure CRF. Single-frequency segmental BIA was used to measure PhA and body composition quantity. Resting Doppler echocardiography and biomarkers were measured to assess cardiac function and systemic inflammation. RESULTS: Compared with patients with lower PhA, patients with higher PhA (above mean 5.8°) presented a greater absolute peak oxygen consumption (VO2; 1.83 [1.3-2.1] versus 1.39 [1.1-1.6] L/min, P = 0.003), VO2 peak adjusted for body weight (17.5 [12.3-18.1] versus 13.3 [12.7-15.2] mL/kg/min, P = 0.040), and a lower edema index (48.7 [2.9] versus 51.4% [2.7], P < 0.001) and N-terminal pro-B-type natriuretic peptide (NT-proBNP; 64 [50-121] versus 183 [68-343.5] pg/dL, P < 0.001). In the overall sample, PhA was correlated with absolute VO2 peak (r = 0.468, P < 0.001), VO2 peak adjusted for body weight (r = 0.368, P = 0.004), VO2 peak adjusted for fat-free mass (r = 0.315, P = 0.015), edema index (r = -0.508, P < 0.001), and NT-proBNP (r = -0.579, P < 0.001). PhA remained a significant predictor for CRF even after adjustment for potential confounders and HFpEF severity. CONCLUSION: In patients with obesity and HFpEF, a greater PhA is an independent predictor for favorable CRF.

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra.

BACKGROUND: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). METHODS: We measured eosinophils in 64 patients with HF (50% females), 55 (51-63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO2) with a treadmill test. RESULTS: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1-0.3] to 0.3 [0.1-0.4] × 103 cells/µL (p < 0.001) and from 0.3 [0.2-0.5] to 0.2 [0.1-0.3] × 103 cells/µL, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO2 (Spearman's Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4-0.6] vs. 0.2 [0.1-0.4] × 103 cells/µL, p = 0.023), who also showed a greater increase in peak VO2 (3.0 [0.9-4.3] vs. 0.3 [-0.6-1.8] mLO2·kg-1·min-1, p = 0.015). CONCLUSION: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO2.

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction.

PURPOSE: - Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique. METHODS: - Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range. RESULTS: - Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56-72] years. Global stress MBF was 2.43 ml/min/g [2.16-2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07-2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81-0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e' and E/e' respectively). CONCLUSION: - Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction.

Contribution of hemoglobin concentration to cardiorespiratory fitness in black African American patients with recently decompensated heart failure and reduced ejection fraction.

BACKGROUND: Previous studies have shown that patients with heart failure with reduced ejection fraction (HFrEF) and anemia have reduced peak oxygen consumption (VO2). Black or African American (B-AA) patients have a higher prevalence of anemia and are underrepresented in clinical studies of HFrEF. The aim of this study was to determine the contribution of hemoglobin to peak VO2 in B-AA patients recently hospitalized for acute decompensated HFrEF. METHODS: We analyzed cardiopulmonary exercise testing (CPX) data measured within two weeks of discharge for acute decompensated HF in B-AA patients with HFrEF (left ventricular ejection fraction [LVEF] ≤40%) without severe anemia (Hb<8 g/dL). Blood samples were collected prior to CPX. Data are reported as median [interquartile range] and compared between groups with the Mann-Whitney, Chi-Square, and Spearman's rank tests. RESULTS: We included 81 patients; 27 (33%) women, 57 [27-79] years of age, Body Mass Index of 33 [15-55] kg/m2 and LVEF of 30 [23-36] %. Hemoglobin ranged between 9.1 to 18.1 g/dL (median= 13.3 [11.9-14.5] g/dL); 26 (32%) were considered to have anemia based on a Hb concentration of males <13 g/dL and females <12 g/dL. Peak VO2 was lower in patients with anemia (11.8 [10.0-14.2] vs. 14.1 [10.6-17.0] mL·kg-1·min-1; P=0.010) with a significant correlation between peak VO2 and hemoglobin concentration (R=+0.455; P<0.001). CONCLUSIONS: Anemia is prevalent among B-AA patients with recently decompensated HFrEF and appears to be a significant contributor to reductions in peak VO2.

Nonpharmacological Strategies in Heart Failure with Preserved Ejection Fraction.

Patients with heart failure with preserved ejection fraction (HFpEF) suffer from a high rate of cardiometabolic comorbidities with limited pharmaceutical therapies proven to improve clinical outcomes and cardiorespiratory fitness (CRF). Nonpharmacologic therapies, such as exercise training and dietary interventions, are promising strategies for this population. The aim of this narrative review is to present a summary of the literature published to date and future directions related to the efficacy of nonpharmacologic, lifestyle-related therapies in HFpEF, with a focus on exercise training and dietary interventions.

Sarcopenic Obesity Is Associated With Reduced Cardiorespiratory Fitness Compared With Nonsarcopenic Obesity in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Sarcopenia impairs cardiorespiratory fitness (CRF) in patients with heart failure with reduced ejection fraction (HFrEF). Obesity has also been shown to impair CRF; however, the effects of sarcopenia on CRF in patients with obesity and HFrEF are unknown. The aim of this analysis was to examine differences in CRF between patients with sarcopenic obesity (SO) and non-SO (NSO) with HFrEF. We also assessed associations between skeletal muscle mass index (SMMI) and CRF. METHODS: Forty patients with HFrEF and obesity underwent cardiopulmonary exercise testing to collect measures of CRF including peak oxygen consumption (VO2), circulatory power, oxygen uptake efficiency slope, O2 pulse, and exercise time. Body composition was performed in all patients using bioelectrical impedance analysis to quantify fat mass index and divide patients into SO and NSO based on SMMI cutoffs. Results are presented as mean (SD) or median [interquartile range] as appropriate. RESULTS: Nearly half (43% [n=17]) of patients had SO. Patients with SO had a lower SMMI than those with NSO, and no differences in fat mass index were observed between groups. Those with SO achieved a lower absolute peak VO2 (NSO, 1.62±0.53 L·min-1 versus SO, 1.27±0.44 L·min-1, P=0.035), oxygen uptake efficiency slope (NSO, 1.92±0.59 versus SO, 1.54±0.48, P=0.036), and exercise time (NSO, 549±198 seconds versus SO, 413±140 seconds, P=0.021) compared to those with NSO. On multivariate analysis, SMMI remained a significant predictor of absolute peak VO2 when adjusted for age, sex, adiposity, and HF severity. CONCLUSIONS: In patients with HFrEF and obesity, sarcopenia, defined as low SMMI, is associated with a clinically significant reduction in CRF, independent of adiposity.

Physical activity, sedentary behaviors and all-cause mortality in patients with heart failure: Findings from the NHANES 2007-2014.

BACKGROUND: Limited data are available examining the effects of both moderate- and vigorous-intensity physical activity (MVPA) and sedentary behavior (SB) on longevity among patients with heart failure (HF). This study examined the associations of MVPA and SB with all-cause mortality in HF patients using a nationally representative survey data. METHODS: National Health and Nutrition Examination Survey data (2007-2014) were used. 711 adults with self-reported congestive HF, linked to 2015 mortality data were analyzed. Self-reported MVPA and SB minutes were used to create the three MVPA [No-MVPA, insufficient (I-MVPA; <150 min/wk), and sufficient (S-MVPA; ≥150 min/wk)] and two SB (<8 and ≥8 hrs/d) groups. Cox proportional hazard models were constructed to test the associations of MVPA and SB with all-cause mortality. RESULTS: 119 deaths occurred over an average of 4.9 years of follow-up. Lower MVPA and higher SB were independently associated with poor survival (P < .001). Joint and stratified analyses showed that the protective effect of MVPA was most pronounced among patients with SB<8 hrs/d. There was no difference in the mortality risk by SB levels within I-MVPA and S-MVPA groups; however, in the No-MVPA group, those with SB≥8 hrs/d had a greater risk of mortality compared to those with <8 hrs/d (Hazard ratio = 1.60). CONCLUSION: In this HF cohort, MVPA and SB were independently and jointly associated with all-cause mortality. The beneficial effect of MVPA is attenuated by excessive SB; however, engaging in some amount of MVPA may provide a protective effect and attenuates the detrimental effects associated with excessive SB.

Effects of Replacing Sedentary Time With Physical Activity on Mortality Among Patients With Heart Failure: National Health and Nutrition Examination Survey Follow-Up Study.

A sedentary lifestyle is prevalent among patients with heart failure (HF) and is associated with poor prognosis and survival, possibly owing to the displacement of health-enhancing behaviors, such as physical activity (PA). However, there is limited evidence examining the displacement effects of reducing duration of sedentary time (ST) on clinical outcomes in patients with HF. The current study examined the theoretical effects of relocating ST with PA on all-cause and cardiovascular disease (CVD)-specific mortality risks in patients with HF. We analyzed 265 patients with HF who participated in the National Health and Nutrition Examination Survey from 2003 to 2006. Cox proportional hazards regression model was fitted to estimate mortality risks based on objectively measured ST well as time spent in light-intensity PA (LPA) and moderate- and vigorous-intensity PA (MVPA). The theoretical changes in the hazard ratio (HR) by replacing ST with LPA or MVPA were examined using isotemporal substitutional modeling. On average, patients with HF spent 70% of waking hours per day in ST (9.01 hours), followed by LPA (29%; 3.75 hours) and MVPA (1%; 0.13 hours). Ten-minute substitution of ST with LPA was associated with significantly lower all-cause and CVD-specific mortality risks (hazard ratio [HR]=0.93 for both). The mortality risks progressively decreased as more ST was relocated to LPA. The relocation effects of ST with MVPA were not statistically significant, possibly because of limited MVPA accrued in this clinical population. The current study provides empirical evidence about the potential health benefits of replacing a modest amount of ST with LPA among patients with HF.

Patient Perceptions of Exertion and Dyspnea With Interleukin-1 Blockade in Patients With Recently Decompensated Systolic Heart Failure.

Interleukin-1 (IL-1) blockade is an anti-inflammatory treatment that may affect exercise capacity in heart failure (HF). We evaluated patient-reported perceptions of exertion and dyspnea at submaximal exercise during cardiopulmonary exercise testing (CPET) in a double-blind, placebo-controlled, randomized clinical trial of IL-1 blockade in patients with systolic HF (REDHART [Recently Decompensated Heart Failure Anakinra Response Trial]). Patients underwent maximal CPET at baseline, 2, 4, and 12 weeks and rated their perceived level of exertion (RPE, on a scale from 6 to 20) and dyspnea on exertion (DOE, on a scale from 0 to 10) every 3 minutes throughout exercise. Patients also answered 2 questionnaires to assess HF-related quality of life: the Duke Activity Status Index and the Minnesota Living with Heart Failure Questionnaire. From baseline to the 12-week follow-up, IL-1 blockade significantly reduced RPE and DOE at 3- and 6-minutes during CPET without changing values for heart rate, oxygen consumption, and cardiac workload at 3- and 6-minutes. Linear regression identified 6-minute RPE to be a strong independent predictor of both physical symptoms (Minnesota Living with Heart Failure Questionnaire; ß = 0.474, p = 0.002) and perceived exercise capacity (Duke Activity Status Index; ß = -0.443, p = 0.008). In conclusion, patient perceptions of exertion and dyspnea at submaximal exercise may be valuable surrogates for quality of life and markers of response to IL-1 blockade in patients with HF.

Midpoint of energy intake, non-fasting time and cardiorespiratory fitness in heart failure with preserved ejection fraction and obesity.

BACKGROUND: Delayed time of evening meal is associated with favorable cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. It is unknown, however, if increasing daily non-fasting time or delaying the midpoint of energy intake may also be associated with CRF. OBJECTIVE: Our aim was to examine whether a longer non-fasting time, delayed midpoint of energy intake, or both, are associated with greater CRF in patients with HFpEF and obesity. METHODS: We measured peak oxygen consumption (VO2), a measure of CRF, in 32 patients with HFpEF and obesity with cardiopulmonary exercise testing, and dietary intake using a five-pass 24-h dietary recall. Participants were divided into groups by having lesser (<11.6) or greater (≥11.6) periods of non-fasting time than the median and similarly, with earlier (<2:15 PM) or later (≥2:15 PM) than median midpoint of energy intake. RESULTS: Median non-fasting time was 11.6 [10.6-12.9] hours and midpoint of energy intake was 2:15 [1:04-3:00] PM. There were no differences in CRF between those with a shorter (<11.6) or longer (≥11.6) non-fasting time. Participants with a delayed midpoint of energy intake (≥2:15 PM) had greater peak VO2 and exercise time. Midpoint of energy intake (r = 0.444, P = 0.011) and time of last meal (r = 0.550, P = 0.001) displayed a positive association with peak VO2, but not non-fasting time nor time of first meal. CONCLUSIONS: Delaying the midpoint of energy intake by postponing last meal is associated with better peak VO2 and exercise time in patients with HFpEF and obesity.

Peak oxygen consumption achieved at the end of cardiac rehabilitation predicts long-term survival in patients with coronary heart disease.

AIMS: Cardiac rehabilitation (CR) improves survival in patients with coronary heart disease (CHD), which is largely mediated by the improvements in cardiorespiratory fitness (CRF) defined as peak oxygen consumption (VO2). Therefore, measuring CRF is essential to predict long-term outcomes in this population. It is unclear, however, whether peak VO2 achieved at the end of CR (END-peak VO2) predicts survival or whether the changes of CRF achieved during CR provide a greater prognostic value. To determine whether END-peak VO2 independently predicts long-term survival in patients with CHD undergoing CR. We also aimed at identifying cut-offs for END-peak VO2 that could be used in clinical practice. METHODS AND RESULTS: Retrospective analysis of 853 patients with CHD referred to CR who completed a maximal cardiopulmonary exercise test. Survival analysis was performed to examine the risk of all-cause mortality (average follow-up years: 6.65) based on peak VO2. The Contal and O'Quigley's method was used to determine the optimal cut-off of END-peak VO2 based on the log-rank statistic. END-peak VO2 was inversely associated with mortality risk [hazard ratio (HR) = 0.84; 95% confidence interval (CI) = 0.78-0.90], independent of changes in peak VO2 adjusted for the baseline peak VO2. The estimated cut-off of END-peak VO2 at ≥17.6 mL/kg/min best predicted the survival with high predictive accuracy and patients with END-peak VO2 under the cut-off had a greater risk of mortality (HR = 2.93; 95% CI = 1.81-4.74). CONCLUSIONS: In patient with CHD undergoing CR, END-peak VO2 is an independent predictor for long-term survival. Studies utilizing higher intensity CR programmes, with and without pharmacologic strategies, to increase peak VO2 to a greater degree in those achieving a suboptimal END-peak VO2, are urgently needed.