Apostolos Tsimploulis

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.

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

OBJECTIVE To assess the association between exercise capacity and the risk of developing chronic kidney disease (CKD). PATIENTS AND METHODS Exercise 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. RESULTS During 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. CONCLUSION Higher exercise capacity attenuated the risk of developing CKD. The association was independent and graded.

Exercise Capacity and Atrial Fibrillation Risk in Veterans: A Cohort Study.

OBJECTIVE To assess the association between exercise capacity and the risk of developing atrial fibrillation (AF). PATIENTS AND METHODS A symptom-limited exercise tolerance test was conducted to assess exercise capacity in 5962 veterans (mean age, 56.8±11.0 years) from the Veterans Affairs Medical Center, Washington, DC. None had evidence of AF or ischemia at the time of or before undergoing their exercise tolerance test. We established 4 fitness categories based on age-stratified quartiles of peak metabolic equivalent task (MET) achieved: least fit (4.9±1.10 METs; n=1446); moderately fit (6.7±1.0 METs; n=1490); fit (7.9±1.0 METs; n=1585), and highly fit (9.3±1.2 METs; n=1441). Multivariable Cox proportional hazards regression models were used to compare the AF-exercise capacity association between fitness categories. RESULTS During a median follow-up period of 8.3 years, 722 (12.1%) individuals developed AF (14.5 per 1000 person-years; 95% CI, 13.9-15.9 per 1000 person-years). Exercise capacity was inversely related to AF incidence. The risk was 21% lower (hazard ratio, 0.79; 95% CI, 0.76-0.82) for each 1-MET increase in exercise capacity. Compared with the least fit individuals, hazard ratios were 0.80 (95% CI, 0.67-0.97) for moderately fit individuals, 0.55 (95% CI, 0.45-0.68) for fit individuals, and 0.37 (95% CI, 0.29-0.47) for highly fit individuals. Similar trends were observed in those younger than 65 years and those 65 years or older. CONCLUSION Increased fitness is inversely and independently associated with the reduced risk of developing AF. The decrease in risk was graded and precipitous with only modest increases in exercise capacity. These findings counter previous suggestions that even moderate increases in physical activity, as recommended by national and international guidelines, increase the risk of AF, with marked protection against AF noted with increasing levels of fitness.

Heart Rate at Rest, Exercise Capacity, and Mortality Risk in Veterans

Heart rate (HR) at rest has been associated inversely with mortality risk. However, fitness is inversely associated with mortality risk and both increased fitness and β-blockade therapy affect HR at rest. Thus, both fitness and β-blockade therapy should be considered when HR at rest-mortality risk association is assessed. From 1986 to 2011, we assessed HR at rest, fitness, and mortality in 18,462 veterans (mean age = 58 ± 11 years) undergoing a stress test. During a median follow-up period of 10 years (211,398 person-years), 5,100 died, at an average annual mortality of 24.1 events/1,000 person-years. After adjusting for age, body mass index, cardiac risk factors, medication, and exercise capacity, we noted approximately 11% increase in risk for each 10 heart beats. To assess the risk in a wide and clinically relevant spectrum, we established 6 HR at rest categories per 10 heart beat intervals ranging from <60 to ≥100 beats. Mortality risk was significantly elevated at a HR at rest of ≥70 beats/min (hazard ratio 1.14, confidence interval 1.04 to 1.25; p <0.006) and increased progressively to 49% (hazard ratio 1.49, confidence interval 1.29 to 1.73; p <0.001) for those with a HR at rest of ≥100 beats/min. Similar trends were noted when for subjects aged <60 and ≥60 years and those treated with β blockers. In all assessments, mortality risk was consistently overestimated when fitness was not considered. In conclusion, HR at rest-mortality risk association was direct and independent. A progressive increase in risk was noted >70 beats/min for the entire cohort, those treated with β blockers, and those aged <60 and ≥60 years. Mortality risk was overestimated slightly when fitness status was not considered.

Systolic–diastolic hypertension versus isolated systolic hypertension and incident heart failure in older adults: Insights from the Cardiovascular Health Study

BACKGROUND Isolated systolic hypertension (ISH) is common in older adults and is a risk factor for incident heart failure (HF). We examined the association of systolic-diastolic hypertension (SDH) with incident HF and other outcomes in older adults. METHODS In the Cardiovascular Health Study (CHS), 5776 community-dwelling adults≥65years had data on baseline systolic and diastolic blood pressure (SBP and DBP). We excluded those with DBP<60mmHg (n=821), DBP≥90 and SBP<140mmHg (n=28), normal BP, taking anti-hypertensive drugs (n=1138), normal BP, not taking anti-hypertensive drugs, history of hypertension (n=193), and baseline HF (n=101). Of the remaining 3495, 1838 had ISH (SBP≥140 and DBP<90mmHg) and 240 had SDH (SBP≥140 and DBP≥90mmHg). The main outcome was centrally-adjudicated incident HF over 13years of follow-up. RESULTS Participants had a mean (±SD) age of 73 (±6)years, 57% were women, and 16% African American. Incident HF occurred in 25%, 22% and 11% of participants with ISH, SDH and no hypertension, respectively. Compared to no hypertension, multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident HF associated with ISH and SDH were 1.86 (1.51-2.30) and 1.73 (1.23-2.42), respectively. Cardiovascular mortality occurred in 22%, 24% and 9% of those with ISH, SDH and no hypertension, respectively with respective multivariable-adjusted HRs (95% CIs) of 1.88 (1.49-2.37) and 2.30 (1.64-3.24). CONCLUSION Among older adults with hypertension, both SDH and ISH have similar associations with incident HF and cardiovascular mortality.

Isolated diastolic hypertension and incident heart failure in community-dwelling older adults: Insights from the Cardiovascular Health Study

BACKGROUND Isolated systolic hypertension and isolated diastolic hypotension are common in older adults and associated with a higher risk of incident heart failure (HF). However, little is known about the prevalence and impact of isolated diastolic hypertension in this population. METHODS In the Cardiovascular Health Study (CHS), of the 5776 community-dwelling older adults ≥65years who had data on baseline systolic and diastolic blood pressure (SBP and DBP), 28 had isolated diastolic hypertension (DBP ≥90mmHg and SBP <140mmHg). From the 5748 without isolated diastolic hypertension, we excluded those with SBP ≥120mmHg (n=4451), DBP 80-89mmHg (n=20), DBP <60mmHg (n=425), normal BP taking anti-hypertensive medications (n=311), normal BP taking no anti-hypertensive medications but with history of hypertension (n=38), and baseline HF (n=5). The final cohort of 524 participants included 27 with isolated diastolic hypertension. RESULTS Patients (n=524) had a mean (±SD) age of 71 (±5) years, 58% were women and 9% African American. There were no significant between-group age or sex differences; 37% of those with isolated diastolic hypertension (versus 7% without) were African American. Incident HF occurred in 19% and 7% of participants with and without isolated diastolic hypertension, respectively (multivariable-adjusted hazard ratio {HR}, 4.65; 95% confidence interval {CI}, 1.09-19.90; p=0.038). There was a trend toward higher cardiovascular mortality (HR, 4.59; 95% CI, 0.92-23.88; p=0.063). CONCLUSION Among community-dwelling older adults, isolated diastolic hypertension is rare and is associated with higher risk for incident HF and cardiovascular mortality.

PDE5 Inhibitors for the Treatment of Erectile Dysfunction in Patients with Hypertension

Erectile dysfunction (ED) is defined as the inability to develop or maintain a penile erection during sexual performance. Its prevalence ranges from 25 % [1] to 52 % [2] among male adults aged 40–70 years. ED is an important risk factor for cardiovascular events [3, 4]. ED may also lower adherence to therapy in patients with chronic diseases, especially hypertension, since many antihypertensive medications have unfavorable effects on libido [5, 6].

SMOKING AND OUTCOMES IN OLDER PATIENTS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION (HFPEF)

Cigarette smoking is a risk factor for heart failure (HF; PMC5499230), but in patients hospitalized for HF smoking has a paradoxical short-term beneficial association (PMID: 18487210). We examined the association of smoking with long-term outcomes in HFpEF. Of the 8873 patients hospitalized for HF

ASSOCIATIONS OF SYSTOLIC BLOOD PRESSURE (SBP) <120 (VERSUS 120-139) MMHG WITH OUTCOMES IN PATIENTS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION (HFPEF) WITHOUT HYPERTENSION (HTN)

According to the 2017 update of 2013 ACCF/AHA HF guideline, SBP should be lowered to <130 mmHg in patients with HFpEF and HTN. However, less is known about the association of lower SBP and outcomes in HFpEF without HTN. Of the 8873 hospitalized patients with HF and EF ≥50% in Medicare-linked

HEART FAILURE HOSPITALIZATION (HFH) DESPITE DIGOXIN THERAPY VERSUS NO HFH DESPITE PLACEBO IN THE DIGITALIS INVESTIGATION GROUP (DIG) TRIAL: INSIGHTS INTO RISK FACTORS FOR HFH IN HF AND REDUCED EJECTION FRACTION (HFREF)

Background: In the DIG trial, 6800 patients with HFrEF (EF≤45%) were randomized to receive either placebo (n=3403) or digoxin (n=3397) and followed for a mean of 37 months. Digoxin significantly reduced the risk of HFH by 28% (HR, 0.72; 95% CI, 0.66–0.79). However, 27% of patients in the digoxin