Impact of the COVID-19 Pandemic on the Provision of Dialysis Service and Mortality in Veterans Receiving Maintenance Hemodialysis in the VA: An Interrupted Time-Series Analysis.

INTRODUCTION: According to the US Renal Data System (USRDS), patients with end-stage kidney disease (ESKD) on maintenance dialysis had higher mortality during early COVID-19 pandemic. Less is known about the effect of the pandemic on the delivery of outpatient maintenance hemodialysis and its impact on death. We examined the effect of pandemic-related disruption on the delivery of dialysis treatment and mortality in patients with ESKD receiving maintenance hemodialysis in the Veterans Health Administration (VHA) facilities, the largest integrated national healthcare system in the USA. METHODS: Using national VHA electronic health records data, we identified 7,302 Veterans with ESKD who received outpatient maintenance hemodialysis in VHA healthcare facilities during the COVID-19 pandemic (February 1, 2020, to December 31, 2021). We estimated the average change in the number of hemodialysis treatments received and deaths per 1,000 patients per month during the pandemic by conducting interrupted time-series analyses. We used seasonal autoregressive moving average (SARMA) models, in which February 2020 was used as the conditional intercept and months thereafter as conditional slope. The models were adjusted for seasonal variations and trends in rates during the pre-pandemic period (January 1, 2007, to January 31, 2020). RESULTS: The number (95% CI) of hemodialysis treatments received per 1,000 patients per month during the pre-pandemic and pandemic periods were 12,670 (12,525-12,796) and 12,865 (12,729-13,002), respectively. Respective all-cause mortality rates (95% CI) were 17.1 (16.7-17.5) and 19.6 (18.5-20.7) per 1,000 patients per month. Findings from SARMA models demonstrate that there was no reduction in the dialysis treatments delivered during the pandemic (rate ratio: 0.999; 95% CI: 0.998-1.001), but there was a 2.3% (95% CI: 1.5-3.1%) increase in mortality. During the pandemic, the non-COVID hospitalization rate was 146 (95% CI: 143-149) per 1,000 patients per month, which was lower than the pre-pandemic rate of 175 (95% CI: 173-176). In contrast, there was evidence of higher use of telephone encounters during the pandemic (3,023; 95% CI: 2,957-3,089), compared with the pre-pandemic rate (1,282; 95% CI: 1,241-1,324). CONCLUSIONS: We found no evidence that there was a disruption in the delivery of outpatient maintenance hemodialysis treatment in VHA facilities during the COVID-19 pandemic and that the modest rise in deaths during the pandemic is unlikely to be due to missed dialysis.

Cardiorespiratory fitness and risk of Alzheimer's disease and related dementias among American veterans.

INTRODUCTION: Cardiorespiratory fitness (CRF) is associated with improved health and survival. Less is known about its association with Alzheimer's disease and related dementias (ADRD). METHODS: We identified 649,605 US veterans 30 to 95 years of age and free of ADRD who completed a standardized exercise tolerance test between 2000 and 2017 with no evidence of ischemia. We examined the association between five age- and sex-specific CRF categories and ADRD incidence using multivariate Cox regression models. RESULTS: During up to 20 (median 8.3) years of follow-up, incident ADRD occurred in 44,105 (6.8%) participants, with an incidence rate of 7.7/1000 person-years. Compared to the least-fit, multivariable-adjusted hazard ratios (95% confidence intervals) for incident ADRD were: 0.87 (0.85-0.90), 0.80 (0.78-0.83), 0.74 (0.72-0.76), and 0.67 (0.65-0.70), for low-fit, moderate-fit, fit, and high-fit individuals, respectively. DISSCUSSION: These findings demonstrate an independent, inverse, and graded association between CRF and incident ADRD. Future studies may determine the amount and duration of physical activity needed to optimize ADRD risk reduction.

In-Hospital Weight Loss and Outcomes in Patients With Heart Failure.

BACKGROUND: Acute decompensation of heart failure (HF) is often marked by fluid retention, and weight loss is a marker of successful diuresis. We examined the relationship between in-hospital weight loss and post-discharge outcomes in patients with HF. METHODS: We conducted a propensity score-matched study of 8830 patients hospitalized for decompensated HF in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, in which 4415 patients in the weight-loss group and 4415 patients in the no-weight-loss group were balanced on 75 baseline characteristics. We defined weight loss as an admission-to-discharge weight loss of 1-30 kilograms, and we defined no weight loss as a weight gain or loss of < 1 kilogram. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with weight loss were estimated. RESULTS: Patients had a mean age of 78 years, 57% were women, and 11% were African American. The median weight loss in the weight-loss group was 3.6 (interquartile range, 2.0-6.0) kilograms. HRs and 95% CIs for 30-day all-cause mortality, all-cause readmission and HF readmission associated with weight loss were 0.75 (0.63-0.90), 0.90 (0.83-0.99) and 0.83 (0.72-0.96), respectively. Respective 60-day HRs (95% CIs) were 0.80 (0.70-0.92), 0.91 (0.85-0.98) and 0.88 (0.79-0.98). These associations were attenuated and lost significance during 6 months of follow-up. CONCLUSIONS: Among older patients hospitalized for decompensated HF, in-hospital weight loss was associated with a lower risk of mortality and hospital readmission. These findings suggest that in-hospital weight loss, a marker of successful diuresis and decongestion, is also a marker of improved clinical outcomes.

Right Ventricular Ejection Fraction and Beta-Blocker Effect in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: A low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown. METHODS AND RESULTS: Of the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75-1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78-1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55-0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83-1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251). CONCLUSIONS: The effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy.

Opioid Use and Outcomes in Hospitalized Older Patients With Heart Failure Receiving and Not Receiving Hospice Referrals.

BACKGROUND: The use of opioids is associated with poor outcomes. Less is known about this association in patients with heart failure (HF) and whether it varies by the receipt of hospice care. METHODS: Of the 7467 patients hospitalized for HF without previous opioid use, 124 received discharge opioids. We matched 123 of these patients with 123 not receiving opioids based on their propensity scores for opioid use, thus assembling a matched cohort of 246 patients balanced on 30 baseline characteristics (mean age, 76 years, 60% women, and 11% African American). We repeated the process in hospice (n = 155; 20 received opioids) and nonhospice (n = 7298; 104 received opioids) subgroups, thus assembling 2 matched cohorts of 22 and 208 patients, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) associated with opioid use were estimated from matched cohorts. RESULTS: During 8.6 (median, 1.4) years of follow-up, all-cause mortality occurred in 80% and 68% of matched patients in the opioid and nonopioid groups, respectively (HR, 1.49; 95% CI, 1.11-1.99; P = 0.008). There was evidence of heterogeneity in this association between hospice and nonhospice patients (P for interaction, 0.027). Among matched hospice and nonhospice patients, HRs (95% CIs) for mortality were 6.37 (2.06-19.69; P = 0.001) and 1.42 (1.03-1.96; P = 0.035), respectively. HRs (95% CIs) for 30-day and 1-year mortality were 1.98 (1.06-3.70; P = 0.033) and 1.72 (1.18-2.49; P = 0.004), respectively. HRs (95% CIs) for all-cause, HF, and non-HF readmissions were 1.31 (0.97-1.76; P = 0.079), 1.03 (0.71-1.49; P = 0.866), and 1.75 (1.05-2.91; P = 0.031), respectively. Readmission associations were similar among matched nonhospice patients. There was no readmission among matched hospice patients receiving opioids. CONCLUSIONS: In older patients with HF, opioid use is associated with a higher risk of mortality, which is greater in the hospice subgroup, and a higher risk of non-HF readmission in the nonhospice subgroup.

Renin-Angiotensin Inhibition and Outcomes in Nursing Home Residents With Heart Failure.

BACKGROUND: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs-ARBs) improve outcomes in heart failure (HF). Less is known about this association in nursing home (NH) residents. METHODS: Of the 8024 hospitalized HF patients, 542 were NH residents, of whom 250 received ACEIs-ARBs. We assembled a propensity score-matched cohort of 157 pairs of NH residents receiving and not receiving ACEIs-ARBs balanced on 29 baseline characteristics (mean age, 83 years, 74% women, 17% African American), in which we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with ACEI-ARB use. We then checked for interaction in a matched cohort of 5130 patients (378 were NH residents) assembled from the 8024 patients. RESULTS: Among 314 matched NH residents, HRs (95% CIs) for 30-day all-cause readmission, HF readmission, and all-cause mortality were 0.78 (0.47-1.28), 0.68 (0.29-1.60), and 1.26 (0.70-2.27), respectively. Respective HRs (95% CIs) at 1 year were 0.76 (0.56-1.02), 0.68 (0.42-1.09), and 1.04 (0.78-1.38). Among 5130 matched patients, ACEI-ARB use was associated with a significantly lower risk of all outcomes at both times, with no significant interactions, except for 1-year mortality, which was only significant in the non-NH subgroup (P for interaction, 0.026). CONCLUSIONS: We found no evidence that the use of ACEIs or ARBs is associated with improved outcomes in patients with HF in the NH setting. However, we also found no evidence that this association is different in NH residents with HF versus non-NH patients with HF. Future larger studies are needed to demonstrate effectiveness of these drugs in the NH setting.

Impact of Acute Kidney Injury in Patients Hospitalized With Pneumonia.

OBJECTIVES: Pneumonia is a common cause of hospitalization and can be complicated by the development of acute kidney injury. Acute kidney injury is associated with major adverse kidney events (death, dialysis, and durable loss of renal function [chronic kidney disease]). Because pneumonia and acute kidney injury are in part mediated by inflammation, we hypothesized that when acute kidney injury complicates pneumonia, major adverse kidney events outcomes would be exacerbated. We sought to assess the frequency of major adverse kidney events after a hospitalization for either pneumonia, acute kidney injury, or the combination of both. DESIGN AND SETTING: We conducted a retrospective database analysis of the national Veterans Affairs database for patients with a admission diagnosis of International Classification of Diseases-9 code 584.xx (acute kidney injury) or 486.xx (pneumonia) between October 1, 1999, and December 31, 2005. Three groups of patients were created, based on the diagnosis of the index admission and serum creatinine values: 1) acute kidney injury, 2) pneumonia, and 3) pneumonia with acute kidney injury. Patients with mean baseline estimated glomerular filtration rate less than 45 mL/min/1.73 m were excluded. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was major adverse kidney events defined as the composite of death, chronic dialysis, or a permanent loss of renal function after the primary discharge. The observations of 54,894 subjects were analyzed. Mean age was 68.7 ± 12.3 years. The percentage of female was 2.4, 73.3% were Caucasian, and 19.7% were African-American. Differences across the three diagnostic groups were significant for death, 25% decrease in estimated glomerular filtration rate from baseline, major adverse kidney events following admission, and major adverse kidney events during admission (all p < 0.0001). Death alone and major adverse kidney events after discharge were most common in the pneumonia + acute kidney injury group (51% died and 62% reached major adverse kidney events). In both unadjusted and adjusted time to event analyses, patients with pneumonia + acute kidney injury were most likely to die or reach major adverse kidney events. CONCLUSIONS: When acute kidney injury accompanies pneumonia, postdischarge outcomes are worse than either diagnosis alone. Patients who survive a pneumonia hospitalization and develop acute kidney injury are at high risk for major adverse kidney events including death and should receive careful follow-up.

High serum creatinine nonlinearity: a renal vital sign?

Patients with chronic kidney disease (CKD) may have nonlinear serum creatinine concentration (SC) trajectories, especially as CKD progresses. Variability in SC is associated with renal failure and death. However, present methods for measuring SC variability are unsatisfactory because they blend information about SC slope and variance. We propose an improved method for defining and calculating a patient's SC slope and variance so that they are mathematically distinct, and we test these methods in a large sample of US veterans, examining the correlation of SC slope and SC nonlinearity (SCNL) and the association of SCNL with time to stage 4 CKD (CKD4) and death. We found a strong correlation between SCNL and rate of CKD progression, time to CKD4, and time to death, even in patients with normal renal function. We therefore argue that SCNL may be a measure of renal autoregulatory dysfunction that provides an early warning sign for CKD progression.

Age-specific exercise capacity threshold for mortality risk assessment in male veterans.

BACKGROUND: Mortality risk decreases beyond a certain fitness level. However, precise definition of this threshold is elusive and varies with age. Thus, fitness-related mortality risk assessment is difficult. METHODS AND RESULTS: We studied 18 102 male veterans (8305 blacks and 8746 whites). All completed an exercise test between 1986 and 2011 with no evidence of ischemia. We defined the peak metabolic equivalents (METs) level associated with no increase in all-cause mortality risk (hazard ratio, 1.0) for the age categories of <50, 50 to 59, 60 to 69, and ≥70 years. We used this as the threshold group to form additional age-specific fitness categories based on METs achieved below and above it: least-fit (>2 METs below threshold; n=1692), low-fit (2 METs below threshold; n=4884), moderate-fit (2 METs above threshold; n=4646), fit (2.1-4 METs above threshold; n=1874), and high-fit (>4 METs above threshold; n=1301) categories. Multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality across fitness categories. During follow-up (median=10.8 years), 5102 individuals died. Mortality risk for the cohort and each age category increased for the least-fit and low-fit categories (HR, 1.51; 95% CI, 1.37-1.66; and HR, 1.21; 95% CI, 1.12-1.30, respectively) and decreased for the moderate-fit; fit and high-fit categories (HR, 0.71; 95% CI, 0.65-0.78; HR, 0.63; 95% CI, 0.56-0.78; and HR, 0.49; 95% CI, 0.41-0.58, respectively). The trends were similar for 5- and 10-year mortality risk. CONCLUSION: We defined age-specific exercise capacity thresholds to guide assessment of mortality risk in individuals undergoing a clinical exercise test.

Interactive effects of fitness and statin treatment on mortality risk in veterans with dyslipidaemia: a cohort study.

BACKGROUND: Statins are commonly prescribed for management of dyslipidaemia and cardiovascular disease. Increased fitness is also associated with low mortality and is recommended as an essential part of promoting health. However, little information exists about the combined effects of fitness and statin treatment on all-cause mortality. We assessed the combined effects of statin treatment and fitness on all-cause mortality risk. METHODS: In this prospective cohort study, we included dyslipidaemic veterans from Veterans Affairs Medical Centers in Palo Alto, CA, and Washington DC, USA, who had had an exercise tolerance test between 1986, and 2011. We assigned participants to one of four fitness categories based on peak metabolic equivalents (MET) achieved during exercise test and eight categories based on fitness status and statin treatment. The primary endpoint was all-cause mortality adjusted for age, body-mass index, ethnic origin, sex, history of cardiovascular disease, cardiovascular drugs, and cardiovascular risk factors. We assessed mortality from Veteran's Affairs' records on Dec 31, 2011. We compared groups with Cox proportional hazard model. FINDINGS: We assessed 10,043 participants (mean age 58·8 years, SD 10·9 years). During a median follow-up of 10·0 years (IQR 6·0-14·2), 2318 patients died, with an average yearly mortality rate of 22 deaths per 1000 person-years. Mortality risk was 18·5% (935/5046) in people taking statins versus 27·7% (1386/4997) in those not taking statins (p<0·0001). In patients who took statins, mortality risk decreased as fitness increased; for highly fit individuals (>9 MET; n=694), the hazard ratio (HR) was 0·30 (95% CI 0·21-0·41; p<0·0001) compared with least fit (≤5 METs) patients (HR 1; n=1060). For those not treated with statins, the HR for least fit participants (n=1024) was 1·35 (95% CI 1·17-1·54; p<0·0001) and progressively decreased to 0·53 (95% CI 0·44-0·65; p<0·0001) for those in the highest fitness category (n=1498). INTERPRETATION: Statin treatment and increased fitness are independently associated with low mortality among dyslipidaemic individuals. The combination of statin treatment and increased fitness resulted in substantially lower mortality risk than either alone, reinforcing the importance of physical activity for individuals with dyslipidaemia. FUNDING: None.

Using a board game to reinforce learning.

Experiential gaming strategies offer a variation on traditional learning. A board game was used to present synthesized content of fundamental catheter care concepts and reinforce evidence-based practices relevant to nursing. Board games are innovative educational tools that can enhance active learning.

Long-Term Mortality Risk According to Cardiorespiratory Fitness in Patients Undergoing Coronary Artery Bypass Graft Surgery.

The aim of this study was to evaluate the association between cardiorespiratory fitness (CRF) and long-term survival in United States (US) Veterans undergoing CABG. We identified 14,550 US Veterans who underwent CABG at least six months after completing a symptom-limited exercise treadmill test (ETT) with no evidence of cardiovascular disease. During a mean follow-up period of 10.0 ± 5.4 years, 6502 (43.0%) died. To assess the association between CRF and risk of mortality, we formed the following five fitness categories based on peak workload achieved (metabolic equivalents or METs) prior to CABG: Least-Fit (4.3 ± 1.0 METs (n = 4722)), Low-Fit (6.8 ± 0.9 METs (n = 3788)), Moderate-Fit (8.3 ± 1.1 METs (n = 2608)), Fit (10.2 ± 0.8 METs (n = 2613)), and High-Fit (13.0 ± 1.5 METs (n = 819)). Cox proportional hazard models were used to calculate risk across CRF categories. The models were adjusted for age, body mass index, race, cardiovascular disease, percutaneous coronary intervention prior to ETT, cardiovascular medications, and cardiovascular disease risk factors. P-values < 0.05 using two-sided tests were considered statistically significant. The association between cardiorespiratory fitness and mortality was inverse and graded. For every 1-MET increase in exercise capacity, the mortality risk was 11% lower (HR = 0.89; CI: 0.88-0.90; p < 0.001). When compared to the Least-Fit category (referent), mortality risk was 22% lower in Low-Fit individuals (HR = 0.78; CI: 0.73-0.82; p < 0.001), 31% lower in Moderate-Fit individuals (HR = 0.69; CI: 0.64-0.74; p < 0.001), 52% lower in Fit individuals (HR = 0.48; CI: 0.44-0.52; p < 0.001), and 66% lower in High-Fit individuals (HR = 0.34; CI: 0.29-0.40; p < 0.001). Cardiorespiratory fitness is inversely and independently associated with long-term mortality after CABG in Veterans referred for exercise testing.

Progression to Insulin Therapy in Patients With Type 2 Diabetes According to Cardiorespiratory Fitness, Body Mass Index, and Statin Therapy.

OBJECTIVE: To evaluate the association between statin therapy, cardiorespiratory fitness (CRF), body mass index (BMI), and progression to insulin therapy in type 2 diabetes mellitus (T2DM). METHODS: Participants were patients with T2DM (mean age, 62.7±8.4 years; men, 178,992; women, 8360) not treated with insulin, with no evidence of uncontrolled cardiovascular disease, who completed an exercise treadmill test between October 1, 1999, and September 3, 2020. Of these, 158,578 were treated with statins and 28,774 were not. We established 5 age-specific CRF categories according to peak metabolic equivalents of task achieved during an exercise treadmill test. RESULTS: During a median follow-up period of 9.0 years, 51,182 patients progressed to insulin therapy with an average annual incidence rate of 28.4 events/1000 person-years. The adjusted progression rate was 27% higher in statin-treated patients (hazard ratio [HR], 1.27; 95% CI, 1.24 to 1.31), related directly to BMI and inversely related to CRF. A progressively higher rate was noted in statin-treated vs non-statin-treated patients within all BMI categories, ranging from 23% for normal weight to 90% for those with BMI of 35 kg/m2 and higher. The statin-CRF interaction revealed 43% higher rate in the least-fit statin-treated patients (HR, 1.43; 95% CI, 1.35 to 1.51) and a progressive decline with increased CRF to 30% lower risk in highly fit statin-treated patients (HR, 0.70; 95% CI, 0.66 to 0.75). CONCLUSION: In patients with T2DM, the statin-related progression to insulin therapy was associated with relatively low CRF and high BMI levels. The progression rate was mitigated by increased CRF regardless of BMI. Clinicians should foster regular exercise for patients with T2DM to enhance CRF and to lessen the rate of progression to insulin therapy.

The Association between Cardiorespiratory Fitness and the Risk of Breast Cancer in Women.

INTRODUCTION: Studies have shown an inverse association between the risk of breast cancer in women and physical activity. However, information on the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized test and the risk of developing breast cancer is limited. PURPOSE: To examine the CRF-breast cancer risk association in healthy females. METHODS: This retrospective study was derived from the Exercise Testing and Health Outcomes Study cohort ( n = 750,302). Female participants ( n = 44,463; mean age ± SD; 55.1 ± 8.9 yr) who completed an exercise treadmill test evaluation (Bruce protocol) at the Veterans Affairs Medical Centers nationwide from 1999 to 2020 were studied. The cohort was stratified into four age-specific CRF categories (Least-fit, Low-fit, Moderate-fit, and Fit), based on the peak METs achieved during the exercise treadmill test. RESULTS: During 438,613 person-years of observation, 994 women developed breast cancer. After controlling for covariates, the risk of breast cancer was inversely related to exercise capacity. For each 1-MET increase in CRF, the risk of cancer was 7% lower (HR, 0.93; 95% CI, 0.90-0.95; P < 0.001). When risk was assessed across CRF categories with the Least-fit group as the referent, the risk was 18% lower for Low-fit women (HR, 0.82; 95% CI, 0.70-0.96; P = 0.013), 31% for Moderate-fit (HR, 0.69; 95% CI, 0.58-0.82; P < 0.001), and 40% for Fit (HR, 0.60; 95% CI, 0.47-0.75; P < 0.001). CONCLUSIONS: We observed an inverse and graded association between CRF and breast cancer risk in women. Thus, encouraging women to improve CRF may help attenuate the risk of developing breast cancer.

Cardiorespiratory fitness and risk of heart failure with preserved ejection fraction.

AIMS: Preventive strategies for heart failure with preserved ejection fraction (HFpEF) include pharmacotherapies and lifestyle modifications. However, the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized exercise treadmill test (ETT) and the risk of HFpEF has not been evaluated. Thus, we evaluated the association between CRF and HFpEF incidence. METHODS AND RESULTS: We assessed CRF in US Veterans (624 551 men; mean age 61.2 ± 9.7 years and 43 179 women; mean age 55.0 ± 8.9 years) by a standardized ETT performed between 1999 and 2020 across US Veterans Affairs Medical Centers. All had no evidence of heart failure or myocardial infarction prior to completion of the ETT. We assigned participants to one of five age- and gender-specific CRF categories (quintiles) based on peak metabolic equivalents (METs) achieved during the ETT and four categories based on CRF changes in those with two ETT evaluations (n = 139 434) ≥1.0 year apart. During a median follow-up of 10.1 years (interquartile range 6.0-14.3 years), providing 6 879 229 person-years, there were 16 493 HFpEF events with an average annual rate of 2.4 events per 1000 person-years. The adjusted risk of HFpEF decreased across CRF categories as CRF increased, independent of comorbidities. For fit individuals (≥10.5 METs) the hazard ratio (HR) was 0.48 (95% confidence interval [CI] 0.46-0.51) compared with least fit (≤4.9 METs; referent). Being unfit carried the highest risk (HR 2.88, 95% CI 2.67-3.11) of any other comorbidity. The risk of unfit individuals who became fit was 37% lower (HR 0.63, 95% CI 0.57-0.71), compared to those who remained unfit. CONCLUSIONS: Higher CRF levels are independently associated with lower HFpEF in a dose-response manner. Changes in CRF reflected proportional changes in HFpEF risk, suggesting that the HFpEF risk was modulated by CRF.

Stroke Incidence in Patients With Hypertension According to Cardiorespiratory Fitness.

BACKGROUND: Hypertension and physical inactivity are risk factors for stroke. The effect of cardiorespiratory fitness (CRF) on stroke risk in patients with hypertension has not been assessed. We evaluated stroke incidence in patients with hypertension according to CRF and changes in CRF. METHODS: We included 483 379 patients with hypertension (mean age±SD; 59.4±9.0 years) and no evidence of unstable cardiovascular disease as indicated by a standardized exercise treadmill test. Patients were assigned to 5 age- and sex-specific CRF categories based on peak metabolic equivalents achieved at the initial exercise treadmill test and in 4 categories based on metabolic equivalent changes over time (n=110 576). Multivariable Cox models, adjusted for age, and comorbidities were used to estimate hazard ratios and 95% CIs for stroke risk. RESULTS: During a median follow-up of 10.6 (interquartile range, 6.6-14.6) years, 15 925 patients developed stroke with an average yearly rate of 3.1 events/1000 person-years. Stroke risk declined progressively with higher CRF and was 55% lower for the High-fit individuals (hazard ratio, 0.45 [95% CI, 0.42-0.48]) compared with the Least-fit. Similar associations were observed across the race, sex, and age spectra. Poor CRF was the strongest predictor of stroke risk of all comorbidities studied (hazard ratio, 2.24 [95% CI, 2.10-2.40]). Changes in CRF reflected inverse and proportional changes in stroke risk. CONCLUSIONS: Poor CRF carried a greater risk than any of the cardiac risk factors in patients with hypertension, regardless of age, race, or sex. The lower stroke risk associated with improved CRF suggests that increasing physical activity, even later in life, may reduce stroke risk.

Identification and outcomes of KDIGO-defined chronic kidney disease in 1.4 million U.S. Veterans with heart failure.

AIMS: According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes. METHODS AND RESULTS: Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m2, present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m2. Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations. CONCLUSION: Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria.

Blood pressure control among US veterans: a large multiyear analysis of blood pressure data from the Veterans Administration health data repository.

BACKGROUND: Hypertension treatment and control remain low worldwide. Strategies to improve blood pressure control have been implemented in the United States and around the world for several years. This study was designed to assess improvement in blood pressure control over a 10-year period in a large cohort of patients in the Department of Veterans Affairs. METHODS AND RESULTS: A cohort of 582 881 hypertensive patients and 260 924 normotensive individuals treated in 15 Department of Veterans Affairs medical centers between 2000 and 2010 were examined. Strategies used system-wide included blood pressure control as a performance measure, automatic notification to healthcare providers, electronic reminders, and a systematic revisit schedule. The main outcome measure was the percentage of hypertensive patients whose hypertension was controlled and the level of blood pressure each month. In the hypertensive cohort (mean age 62.9±13.4 years, 96.0% male), 52.3% of patients were white, 25.1% were black, and 21.1% were Hispanic. Blood pressure control rates improved from 45.7% in September 2000 to 76.3% in August 2010. Improvements were similar across ethnic, racial, age, and sex groups. Average systolic/diastolic blood pressure decreased from 142.6/77.1 mm Hg in 2000 to 131.2/74.8 mm Hg in 2010, a decrease of 11.3/2.3 mm Hg (P<0.0001 for both). Systolic and diastolic blood pressures were lower in summer than in winter, and this trend continued through 2010. On average, control rates increased by 3.0% per year and were 6.8% higher in summer than in winter. CONCLUSIONS: High rates of blood pressure control can be achieved in all age and ethnic groups and in both sexes.

Gender differences in hypertension: myths and reality.

Life expectancy is longer in women compared to men, and cardiovascular events occur at a lower rate and at a later age in females than males. The impact of gender on the prevalence, the presentation, and the long-term outcome of cardiovascular disease has long been a topic of active research. Gender differences have been found in several studies but opposite findings also exist. The impact of gender in hypertension and antihypertensive therapy remains poorly clarified. The prevalence, awareness, treatment, and control rates of hypertension exhibit some differences between the two sexes, which are age-dependent. The female advantage in the cardiovascular risk of hypertensive patients might be attenuated by comorbidities and target organ damage. Another aspect of major clinical importance is whether gender differences exist on the effects of antihypertensive agents in blood pressure reduction and cardiovascular morbidity and mortality. The aim of this review is to critically evaluate recent data regarding gender differences in hypertension and incorporate new data into the body of existing knowledge.