Charles O. Faselis

Association between AKI and Long-Term Renal and Cardiovascular Outcomes in United States Veterans

BACKGROUND AND OBJECTIVESnAKI is associated with major adverse kidney events (MAKE): death, new dialysis, and worsened renal function. CKD (arising from worsened renal function) is associated with a higher risk of major adverse cardiac events (MACE): myocardial infarction (MI), stroke, and heart failure. Therefore, the study hypothesis was that veterans who develop AKI during hospitalization for an MI would be at higher risk of subsequent MACE and MAKE.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnPatients in the Veterans Affairs (VA) database who had a discharge diagnosis with International Classification of Diseases, Ninth Revision, code of 584.xx (AKI) or 410.xx (MI) and were admitted to a VA facility from October 1999 through December 2005 were selected for analysis. Three groups of patients were created on the basis of the index admission diagnosis and serum creatinine values: AKI, MI, or MI with AKI. Patients with mean baseline estimated GFR<45 ml/min per 1.73 m(2) were excluded. The primary outcomes assessed were mortality, MAKE, and MACE during the study period (maximum of 6 years). The combination of MAKE and MACE-major adverse renocardiovascular events (MARCE)-was also assessed.nnnRESULTSnA total of 36,980 patients were available for analysis. Mean age±SD was 66.8±11.4 years. The most deaths occurred in the MI+AKI group (57.5%), and the fewest (32.3%) occurred in patients with an uncomplicated MI admission. In both the unadjusted and adjusted time-to-event analyses, patients with AKI and AKI+MI had worse MARCE outcomes than those who had MI alone (adjusted hazard ratios, 1.37 [95% confidence interval, 1.32 to 1.42] and 1.92 [1.86 to 1.99], respectively).nnnCONCLUSIONSnVeterans who develop AKI in the setting of MI have worse long-term outcomes than those with AKI or MI alone. Veterans with AKI alone have worse outcomes than those diagnosed with an MI in the absence of AKI.

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.nnMethods 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.nnConclusions— High rates of blood pressure control can be achieved in all age and ethnic groups and in both sexes.nn# Clinical Perspective {#article-title-17}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.

Pattern of Frequent But Nontargeted Pharmacologic Thromboprophylaxis for Hospitalized Patients With Cancer at Academic Medical Centers: A Prospective, Cross-Sectional, Multicenter Study

PURPOSEnHospitalized patients with cancer are considered to be at high risk for venous thromboembolism (VTE). Despite strong recommendations in numerous clinical practice guidelines, retrospective studies have shown that pharmacologic thromboprophylaxis is underutilized in hospitalized patients with cancer.nnnPATIENTS AND METHODSnWe conducted a prospective, cross-sectional study of hospitalized patients with cancer at five academic hospitals to determine prescription rates of thromboprophylaxis and factors influencing its use during hospitalization.nnnRESULTSnA total of 775 patients with cancer were enrolled across five academic medical centers. Two hundred forty-seven patients (31.9%) had relative contraindications to pharmacologic prophylaxis. Accounting for contraindications to anticoagulation, the overall rate of pharmacologic thromboprophylaxis was 74.2% (95% CI, 70.4% to 78.0%; 392 of 528 patients). Among the patients with cancer without contraindications for anticoagulation, individuals hospitalized with nonhematologic malignancies were significantly more likely to receive pharmacologic thromboprophylaxis than those with hematologic malignancies (odds ratio [OR], 2.34; 95% CI, 1.43 to 3.82; P=.007). Patients with cancer admitted for cancer therapy were significantly less likely to receive pharmacologic thromboprophylaxis than those admitted for other reasons (OR, 0.37; 95% CI, 0.22 to 0.61; P<.001). Sixty-three percent of patients with cancer classified as low risk, as determined by the Padua Scoring System, received anticoagulant thromboprophylaxis. Among the 136 patients who did not receive anticoagulation, 58.8% were considered to be high risk by the Padua Scoring System.nnnCONCLUSIONnWe conclude that pharmacologic thromboprophylaxis is frequently administered to hospitalized patients with cancer but that nearly one third of patients are considered to have relative contraindications for prophylactic anticoagulation. Pharmacologic thromboprophylaxis in hospitalized patients with cancer is commonly prescribed without regard to the presence or absence of concomitant risk factors for VTE.

Exercise Capacity and All-Cause Mortality in Male Veterans With Hypertension Aged ≥70 Years

Aging, even in otherwise healthy subjects, is associated with declines in muscle mass, strength, and aerobic capacity. Older individuals respond favorably to exercise, suggesting that physical inactivity plays an important role in age-related functional decline. Conversely, physical activity and improved exercise capacity are associated with lower mortality risk in hypertensive individuals. However, the effect of exercise capacity in older hypertensive individuals has not been investigated extensively. A total of 2153 men with hypertension, aged ≥70 years (mean, 75±4) from the Washington, DC, and Palo Alto Veterans Affairs Medical Centers, underwent routine exercise tolerance testing. Peak workload was estimated in metabolic equivalents (METs). Fitness categories were established based on peak METs achieved, adjusted for age: very-low-fit, 2.0 to 4.0 METs (n=386); low-fit, 4.1 to 6.0 METs (n=1058); moderate-fit, 6.1 to 8.0 METs (n=495); high-fit >8.0 METs (n=214). Cox proportional hazard models were applied after adjusting for age, body mass index, race, cardiovascular disease, cardiovascular medications, and risk factors. All-cause mortality was quantified during a mean follow-up period of 9.0±5.5 years. There were a total of 1039 deaths or 51.2 deaths per 1000 person-years of follow-up. Mortality risk was 11% lower (hazard ratio, 0.89; 95% confidence interval, 0.86–0.93; P<0.001) for every 1-MET increase in exercise capacity. When compared with those achieving ⩽4.0 METs, mortality risk was 18% lower (hazard ratio, 0.82; 95% confidence interval, 0.70–0.95; P=0.011) for the low-fit, 36% for the moderate-fit (hazard ratio, 0.64; 95% confidence interval, 0.52–0.78; P<0.001), and 48% for the high-fit individuals (hazard ratio, 0.52; 95% confidence interval, 0.39–0.69; P<0.001). These findings suggest that exercise capacity is associated with lower mortality risk in elderly men with hypertension.

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.

Exercise capacity and risk of chronic kidney disease in US veterans: a cohort study.

OBJECTIVEnTo assess the association between exercise capacity and the risk of developing chronic kidney disease (CKD).nnnPATIENTS AND METHODSnExercise capacity was assessed in 5812 male veterans (mean age, 58.4±11.5 years) from the Veterans Affairs Medical Center, Washington, DC. Study participants had an estimated glomerular filtration rate of 60 mL/min per 1.73 m(2) or more 6 months before exercise testing and no evidence of CKD. Those who developed CKD during follow-up were initially identified by the International Classification of Diseases, Ninth Revision and further verified by at least 2 consecutive estimated glomerular filtration rate values of less than 60 mL/min per 1.73 m(2) 3 months or more apart. Normal kidney function for CKD-free individuals was confirmed by sequential normal eGFR levels. We established 4 fitness categories on the basis of age-stratified quartiles of peak metabolic equivalents (METs) achieved: least-fit (≤25%; 4.8±0.90 METs; n=1258); low-fit (25.1%-50%; 6.5±0.96 METs; n=1614); moderate-fit (50.1%-75%; 7.7±0.91 METs; n=1958), and high-fit (>75%; 9.5±1.0 METs; n=1436). Multivariable Cox proportional hazard models were used to assess the association between exercise capacity and CKD.nnnRESULTSnDuring a median follow-up period of 7.9 years, 1010 developed CKD (20.4/1000 person-years). Exercise capacity was inversely related to CKD incidence. The risk was 22% lower (hazard ratio, 0.78; 95% CI, 0.75-0.82; P<.001) for every 1-MET increase in exercise capacity. Compared with the least-fit individuals, hazard ratios were 0.87 (95% CI, 0.74-1.03) for low-fit, 0.55 (95% CI, 0.47-0.65) for moderate-fit, and 0.42 (95% CI, 0.33-0.52) for high-fit individuals.nnnCONCLUSIONnHigher exercise capacity attenuated the risk of developing CKD. The association was independent and graded.

Cardiorespiratory Fitness and the Paradoxical BMI-Mortality Risk Association in Male Veterans

OBJECTIVEnTo assess the effect of fitness status on the paradoxical body mass index (BMI)-mortality risk association.nnnPATIENTS AND METHODSnFrom February 1, 1986, through December 30, 2011, we assessed fitness and BMI in 18,033 male veterans (mean age, 58.4 ± 11.4 years) in 2 Veterans Affairs Medical centers. We established 3 fitness categories on the basis of peak metabolic equivalents achieved during an exercise test as well as 5 BMI categories. The primary outcome was all-cause mortality.nnnRESULTSnDuring the follow-up period (median, 10.8 years, comprising a total of 207,168 person-years), 5070 participants (28%) died. After adjusting for age, risk factors, muscle-wasting diseases, medications, and year of entry, mortality risk was higher for individuals with a BMI of 20.1 to 23.9 kg/m(2) (hazard ratio [HR], 1.21; 95% CI, 1.12-1.30) and 18.5 to 20.0 kg/m(2) (HR, 1.56; 95% CI, 1.37-1.77) than for those with a BMI of 24.0 to 27.9 kg/m(2); mortality risk was not increased for those with a BMI of 28.0 kg/m(2) or greater. When stratified by fitness, the trend was similar for low-fit and moderate-fit individuals. However, mortality risk was not increased for high-fit individuals across BMI categories. When fitness status was considered within each BMI category, mortality risk increased progressively with decreased fitness and was more pronounced for moderate-fit (HR, 2.52; 95% CI, 2.06-3.08) and low-fit (HR, 2.48; 95% CI, 2.0-3.06) individuals with a BMI of 18.5-20.0 kg/m(2). Mortality risk was not significantly increased for high-fit individuals (HR, 1.17; 95% CI, 0.78-1.78; P=.45).nnnCONCLUSIONnA high mortality risk associated with low BMI levels was observed only in moderate-fit and low-fit individuals, and not in high-fit individuals. Thus, fitness greatly affects the paradoxical BMI-mortality risk association. Furthermore, our findings indicate that lower BMI levels do not increase the risk for premature death as long as they are associated with high fitness. Thus, the paradoxically higher mortality risk observed with lower body weight as represented by lower BMI is likely the result of unhealthy reduction in body weight and, perhaps most importantly, considerable loss of lean body mass.

Statin Therapy, Fitness, and Mortality Risk in Middle-Aged Hypertensive Male Veterans

BACKGROUNDnHypertension often coexists with dyslipidemia, accentuating cardiovascular risk. Statins are often prescribed in hypertensive individuals to lower cardiovascular risk. Higher fitness is associated with lower mortality, but exercise capacity may be attenuated in hypertension. The combined effects of fitness and statin therapy in hypertensive individuals have not been assessed. Thus, we assessed the combined health benefits of fitness and statin therapy in hypertensive male subjects.nnnMETHODSnPeak exercise capacity was assessed in 10,202 hypertensive male subjects (mean age = 60.4 ± 10.6 years) in 2 Veterans Affairs Medical Centers. We established 4 fitness categories based on peak metabolic equivalents (METs) achieved and 8 categories based on fitness status and statin therapy.nnnRESULTSnDuring the follow-up period (median = 10.2 years), there were 2,991 deaths. Mortality risk was 34% lower (hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.59-0.74; P < 0.001) among individuals treated with statins compared with those not on statins. The fitness-related mortality risk association was inverse and graded regardless of statin therapy status. Risk reduction associated with exercise capacity of 5.1-8.4 METs was similar to that observed with statin therapy. However, those achieving ≥8.5 METs had 52% lower risk (HR = 0.48; 95% CI = 0.37-0.63) when compared with the least-fit subjects (≤5 METs) on statin therapy.nnnCONCLUSIONSnThe combination of statin therapy and higher fitness lowered mortality risk in hypertensive individuals more effectively than either alone. The risk reduction associated with moderate increases in fitness was similar to that achieved by statin therapy. Higher fitness was associated with 52% lower mortality risk when compared with the least fit subjects on statin therapy.

Halting Arterial Aging in Patients with Cardiovascular Disease: Hypolipidemic and Antihypertensive Therapy

Aging is associated with arterial stiffening and subsequent acceleration of pulse wave movement. Traditional cardiovascular risk factors such as hypertension and dyslipidemia are associated with increased arterial stiffness, a premature arterial aging. Antihypertensive drugs exhibit beneficial effects on arterial stiffness, both at the central and peripheral level, and these effects are mainly attributed to blood pressure reduction per se. However, additional benefits of the renin-angiotensin system inhibitors have been recently suggested. Furthermore, a disparity in the effects of beta-blockers on arterial stiffness between conventional and vasodilatory agents has also been suggested. Statin treatment is an essential element of cardiovascular therapy and statins are frequently administered by patients with cardiovascular risk factors or established cardiovascular disease. The effects of statins on arterial stiffness are not yet well established. Moreover, the effects of combining statins with antihypertensive drugs or other strategies to attenuate arterial aging are not adequately studied. The aim of the current review is to present the effects of available therapeutic strategies on arterial stiffness with special emphasis on hypolipidemic and antihypertensive drugs, critically evaluate available information and provide future perspectives in this field.

Carotid Baroreceptor Stimulation: A Promising Approach for the Management of Resistant Hypertension and Heart Failure

Many difficult-to-treat clinical entities in the cardiovascular field are characterized by pronounced sympathetic overactivity, including resistant hypertension and heart failure, underlining the need to explore therapeutic options beyond pharmacotherapy. Autonomic modulation via carotid baroreceptor activation has already been evaluated in clinical trials for resistant hypertension, and relevant outcomes with regard to safety and efficacy of the technique are critically presented. The pathophysiological background of heart failure renders carotid baroreceptor stimulation a potential treatment candidate for the disease. Available data from animal models with heart failure point towards significant cardioprotective benefits of this innovative technique. Accordingly, the effects of baroreceptor activation treatment (BAT) on cardiac parameters of hypertensive patients are well-promising, setting the basis for upcoming clinical trials with baroreflex activation on patients with heart failure. However, as the potential therapeutic of BAT unfolds and new perspectives are highlighted, several concerns are raised that should be meticulously addressed before the wide application of this invasive procedure is set in the limelight.