The differences in renal hemodynamic response following high-intensity exercise between younger and older males.

BACKGROUND: Renal blood flow (RBF) decreases with exercise, but this change is only temporary, and habitual exercise may be an effective method to improve renal function. The kidney shows structural and functional changes with aging, but it is unclear how aging affects the hemodynamic response of the kidneys to exercise. Therefore, we evaluated the differences in the hemodynamic response of the kidneys to high-intensity exercise between younger and older men. METHODS: Sixteen men (8 young and 8 older) underwent an incremental exercise test using a cycle ergometer with a 1-min warm up followed by exercise at 10-20 W/min until the discontinuation criteria were met. Renal hemodynamics were assessed before exercise, immediately after exercise, and at 60-min after exercise using ultrasound echo. RESULTS: High-intensity exercise significantly reduced RBF in both groups (younger: ∆ - 53 ± 16%, p = 0.0005; older: ∆ - 53 ± 19%, p = 0.0004). In the younger group, RBF returned to the pre-exercise level 60-min after exercise (∆ - 0.4 ± 5.7%, p > 0.9999). In contrast, RBF 60-min after exercise was significantly lower than that before exercise in the older group (∆ - 24 ± 19%, p = 0.0006). The older group had significantly lower RBF than younger adults 60-min after exercise (423 ± 32 vs. 301 ± 98 mL/min, p = 0.0283). CONCLUSIONS: Our findings demonstrate that RBF following high-intensity exercise recovered 60-min after exercise in younger group, whereas RBF recovery was delayed in the older group.

Association between high-density lipoprotein cholesterol levels and major adverse cardiovascular events in patients who underwent coronary computed tomography angiography: FU-CCTA registry.

It is unclear whether higher levels of serum high-density lipoprotein cholesterol (HDL-C) prevent major adverse cardiovascular events (MACE). We prospectively evaluated 501 patients who had undergone coronary computed tomography angiography at Fukuoka University Hospital and either were clinically suspected of having coronary artery disease (CAD) or had at least one cardiovascular risk factor with a follow-up of up to 5 years. The primary endpoint was MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization). The patients were divided into tertiles according to the HDL-C level: 47 mg/dl ≥ HDL-C level [n = 167, lower HDL-C level (L-HDL)], 58 mg/dl ≥ HDL-C level ≥ 48 mg/dl [n = 167, middle HDL-C level (M-HDL)] and HDL-C level ≥ 59 mg/dl [n = 167, higher HDL-C level (H-HDL)] groups. There were significant differences in %CAD among the L-HDL, M-HDL and H-HDL groups. Unexpectedly, there was no difference in %MACE between M-HDL and H-HDL, although %MACE in M-HDL was significantly lower than that in L-HDL (p < 0.05). By a multivariate logistic regression analysis, MACE in H-HDL-C was independently associated with diabetes mellitus (DM) (p = 0.03). A Kaplan-Meier curve according to the HDL subgroup indicated that M-HDL, not H-HDL, enjoyed the greatest freedom from MACE among the 3 groups (log-rank test p = 0.047). Finally, the results of a Cox regression model indicated that L-HDL and H-HDL had significantly higher risk of MACE than M-HDL. In conclusions, patients with middle HDL-C levels, not higher HDL-C levels, showed the greatest freedom from MACE. Patients with higher HDL-C levels need to be strictly managed for DM to prevent MACE.

Effect of exercise intensity on renal blood flow in patients with chronic kidney disease stage 2.

BACKGROUND: Acute exercise reduces renal blood flow (RBF). However, the effect of exercise intensity on RBF in patients with chronic kidney disease (CKD) stage 2 is not known. We investigated the association between RBF and exercise intensity in patients with CKD stage 2 using pulsed Doppler ultrasonography. METHODS: Eight men with CKD stage 2 (cystatin C-based estimate of glomerular filtration rate: 60-89 ml/min/1.73 m2) participated in this study. Using a bicycle ergometer, participants undertook a maximal graded exercise test (MGET) (experiment 1) and a multi-stage exercise test (experiment 2) to determine their lactate threshold (LT). Participants undertook a multi-stage exercise test for 4-min each. Workloads of 60%, 80%, 100%, 120%, and 140% of LT were used in experiment 3. RBF was measured by pulsed Doppler ultrasonography at rest, immediately after exercise, and 1 h after exercise in experiment 1, and at rest and immediately after each exercise bout in experiment 3. RESULTS: Renal blood flow after the MGET was 52% lower than at rest, and did not recover as well as after the exercise test. Cross-sectional area (CSA) was significantly lower after graded exercise. RBF tended to be lower at 100% of LT and was significantly lower at 120% of LT. CSA was significantly lower at 100% of LT. CONCLUSIONS: Renal blood flow does not change during exercise until the LT is reached. These findings may assist in making appropriate exercise recommendations to patients with CKD stage 2.

Association between exercise intensity and renal blood flow evaluated using ultrasound echo.

BACKGROUND: High-intensity exercise reduces renal blood flow (RBF) and may transiently exacerbate renal dysfunction. RBF has previously been measured invasively by administration of an indicator material; however, non-invasive measurement is now possible with technological innovations. This study examined variations in RBF at different exercise intensities using ultrasound echo. METHODS: Eight healthy men with normal renal function (eGFRcys 114 ± 19 mL/min/1.73 m2) participated in this study. Using a bicycle ergometer, participants underwent an incremental exercise test using a ramp protocol (20 W/min) until exhaustion in Study 1 and the lactate acid breaking point (LaBP) was calculated. Participants underwent a multi-stage test at exercise intensities of 60, 80, 100, 120, and 140% LaBP in Study 2. RBF was measured by ultrasound echo at rest and 5 min after exercise in Study 1 and at rest and immediately after each exercise in Study 2. To determine the mechanisms behind RBF decline, a catheter was placed into the antecubital vein to study vasoconstriction dynamics. RESULTS: RBF after maximum exercise decreased by 51% in Study 1. In Study 2, RBF showed no significant decrease until 80% LaBP, and showed a significant decrease (31%) at 100% LaBP compared with at rest (p < 0.01). The sympathetic nervous system may be involved in this reduction in RBF. CONCLUSIONS: RBF showed no significant decrease until 80% LaBP, and decreased with an increase in blood lactate. Reduction in RBF with exercise above the intensity at LaBP was due to decreased cross-sectional area rather than time-averaged flow velocity.

Association Between the Presence or Severity of Coronary Artery Disease and Pericardial Fat, Paracardial Fat, Epicardial Fat, Visceral Fat, and Subcutaneous Fat as Assessed by Multi-Detector Row Computed Tomography.

The associations between the presence or severity of coronary artery disease (CAD) and measurements of various kinds of fat as assessed by multidetector row computed tomography (MDCT) are unclear. We enrolled 300 patients who were clinically suspected to have CAD or who had at least one cardiac risk factor and had undergone MDCT. The number of significantly stenosed coronary vessels (VD), and measurements of pericardial fat index, paracardial fat index, epicardial fat index, visceral fat index, and subcutaneous fat index were quantified using MDCT. Plasma levels of adiponectin, pentaxin-3, and high-sensitivity C-reactive protein factors were also measured. Pericardial fat index, paracardial fat index, and visceral fat index in a CAD group were significantly greater than those in a non-CAD group. In addition, the levels of these fat indices tended to increase as the number of VD increased and were positively correlated with the Gensini score. The area-under-the-curve for paracardial fat index was significantly greater than those for the other parameters of fat index measured by a receiver-operating characteristic curve analysis. The cut-off level of paracardial fat index that gave the greatest sensitivity and specificity for the diagnosis of CAD was 54.9 cm3/m2 (sensitivity 0.710, specificity 0.552). The presence of CAD was independently associated with paracardial fat index, in addition to age and diabetes mellitus, by a multiple logistic regression analysis. In conclusion, paracardial fat index may be a marker for evaluating the presence or severity of CAD.

Effects of Tolvaptan With or Without the Pre-Administration of Renin-Angiotensin System Blockers in Hospitalized Patients With Acute Decompensated Heart Failure.

We examined whether tolvaptan combined with an angiotensin II receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACE-I) is more effective than tolvaptan alone in the treatment of patients with heart failure (HF). Sixty-five hospitalized patients with acute decompensated HF were included in this study. They were divided into 2 groups; an ARB/ACE-I group (n = 44, who received ARB or ACE-I before the use of tolvaptan) and a non-ARB/ACE-I group (n = 21). There were no significant differences in patient characteristics including medications at baseline between the non-ARB/ACE-I and ARB/ACE-I groups with the exception of the percentages of hypertension and ischemic heart disease. Urinary volume (UV) at baseline in the ARB/ACE-I group was slightly higher than that in the non-ARB/ACE-I group. The increase in UV after the use of tolvaptan in the non-ARB/ACE-I group was significantly higher than that in the ARB/ACE-I group. The cardiothoracic ratio and the reduction in body weight were similar between the groups after tolvaptan use. Finally, in a logistic regression analysis, a response to the use of tolvaptan was independently associated with the non-use of ARB/ACE-I, but not with age, gender, body mass index, loop diuretic, or human arterial natriuretic peptide. In conclusion, tolvaptan alone might induce an increase in UV in decompensated HF patients without ARB/ ACE-I, although the treatment of HF with ARB/ACE-I is the first choice strategy.

Visit-to-Visit Variability and Reduction in Blood Pressure After a 3-Month Cardiac Rehabilitation Program in Patients With Cardiovascular Disease.

Visit-to-visit variability (VVV) in blood pressure (BP) has been shown to be a predictor of cardiovascular events. It is unknown whether CR can improve VVV in BP as well as reducing BP. We enrolled 84 patients who had cardiovascular disease (CVD) and participated in a 3-month CR program. We measured systolic and diastolic BP (SBP and DBP), pulse pressure (PP), and heart rate (HR) before exercise training at each visit and determined VVV in BP or HR expressed as the standard deviation of the average BP or HR. Patients who had uncontrolled BP at baseline and who did not change their antihypertensive drugs throughout the study period showed a significant reduction of both SBP and DBP with a decrease in PP after 3 months. Patients who did not change their antihypertensive drugs were divided into larger (L-) and smaller (S-) VVV in the SBP groups and L- and S-VVV in the DBP groups according to the average value of VVV in SBP or DBP. In the L-VVV in the SBP and DBP groups, VVV in SBP and DBP in the 1st month was significantly decreased after the 3rd month in both groups. HR at baseline was significantly decreased after 3 months. In addition, CR induced a significant increase in the level of high-density lipoprotein cholesterol (HDL-C) in blood. In conclusion, CR improved VVV in BP in patients with L-VVV in BP and evoked a significant reduction in HR and an increase in HDL-C. These effects due to the CR program may be cardioprotective.

Usefulness of the cardiopulmonary exercise test up to the anaerobic threshold for pati-ents aged ≥ 80 years with cardiovascular disease on cardiac rehabilitation.

OBJECTIVE: A cardiopulmonary exercise test provides information regarding appropriate exercise intensity, but there have been few reports on its use in patients over 80 years of age. DESIGN: Retrospective observational study. PATIENTS: A total of 511 cardiovascular disease patients who performed a cardiopulmonary exercise test from February 2011 to January 2020 were investigated. METHODS: Patients were stratified according to age: < 70 years, 70-79 years, and ≥ 80 years, and the results of the cardiopulmonary exercise test up to anaerobic threshold were compared. RESULTS: Patients in the < 70 age bracket showed higher oxygen consumption, carbon dioxide output, and ventilatory volume and lower ventilation equivalents per oxygen consumption and carbon dioxide output in all time periods. However, there were no significant differences in these parameters or the work rate (70-79 years of age: 41.4 ± 11.7 watts, vs ≥ 80 years: 42.2 ± 10.9 watts, p = 0.95) or oxygen consumption per body weight at anaerobic threshold (12.2 ± 0.2 ml/min/kg, vs 12.1 ± 0.4 ml/min/kg, p = 0.97) between the 70-79 year age bracket and the ≥ 80 year age bracket. CONCLUSION: Even for cardiovascular disease patients age ≥ 80 years, a cardiopulmonary exercise test up to anaerobic threshold can supply useful information for guiding cardiac rehabilitation.

Effects of high-intensity intermittent exercise versus moderate-intensity continuous exercise on renal hemodynamics assessed by ultrasound echo.

High-intensity intermittent exercise (HIIE) has become attractive for presenting a variety of exercise conditions. However, the effects of HIIE on renal function and hemodynamics remain unclear. This study aimed to compare the effects of HIIE and moderate-intensity continuous exercise (MICE) on renal hemodynamics, renal function, and kidney injury biomarkers. Ten adult males participated in this study. We allowed the participants to perform HIIE or MICE to consider the impact of exercise on renal hemodynamics under both conditions. Renal hemodynamic assessment and blood sampling were conducted before the exercise (pre) and immediately (post 0), 30 min (post 30), and 60 min (post 60) after the exercise. Urine sampling was conducted in the pre, post 0, and post 60 phases. There was no condition-by-time interaction (p = 0.614), condition (p = 0.422), or time effect (p = 0.114) regarding renal blood flow. Creatinine-corrected urinary neutrophil gelatinase-associated lipocalin concentrations increased at post 60 (p = 0.017), but none exceeded the cut-off values for defining kidney injury. Moreover, there were no significant changes in other kidney injury biomarkers at any point. These findings suggest that high-intensity exercise can be performed without decreased RBF or increased kidney injury risk when conducted intermittently for short periods.

Effect of Left Ventricular Diastolic Dysfunction on the Cardiopulmonary Exercise Test in Patients With Cardiovascular Disease.

Left ventricular diastolic dysfunction exists in patients with heart failure with reduced ejection fraction and causes activity restriction and a poor prognosis, but there have been few reports about exercise tolerance in patients with diastolic dysfunction, regardless of left ventricular ejection fraction (LVEF). In this study, 294 cardiovascular disease patients who performed a cardiopulmonary exercise test (CPX) with an adequate examination by echocardiography at Fukuoka University Hospital from 2011 to 2020 were investigated. Patients were divided into groups with grade I and grade II or III diastolic dysfunction according to diagnostic criteria, regardless of LVEF, by echocardiography. After adjusting for age, gender, body mass index, smoking, and LVEF by propensity score matching, we compared the results of CPX between the grade I and grade II/III groups. There were no significant differences in hemodynamic parameters, or in the respiratory exchange ratio, oxygen uptake per body weight, oxygen uptake per heart rate, or parameters of ventilatory volume. Ventilatory equivalents per oxygen uptake and per carbon dioxide output were significantly worse in the grade II/III group from the rest to peak periods during CPX. In conclusion, left ventricular diastolic dysfunction worsens ventilatory efficacy during CPX. This effect potentially contributes to a poor prognosis in left ventricular diastolic dysfunction.

Influence of Discontinuation of Cardiac Rehabilitation in Elderly Outpatients Due to the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has restricted people's activities and necessitated the discontinuation of cardiac rehabilitation (CR) programs for outpatients. In our hospital, CR for outpatients had to be discontinued for 3 months. We investigated the influence of this discontinuation of CR on physical activity, body composition, and dietary intake in cardiovascular outpatients. Method: Seventy-eight outpatients who restarted CR were investigated. We measured body composition, balance test, stage of locomotive syndrome, and food frequency questionnaire (FFQ) results at restart and 3 months later. We also investigated the results of examination that were obtained before discontinuation. Results: With regard to baseline characteristics, the percentage of male was 62.7% (n = 49), and average age and body mass index were 74.1 ± 8.5 years and 24.9 ± 7.0 kg/m2, respectively. Stage of locomotive syndrome and the results of FFQ did not change significantly. The one-leg standing time with eyes open test significantly worsened at restart (p < 0.001) and significantly improved 3 months later (p = 0.007). With regard to body composition, all limb muscle masses were decreased at restart and decreased even further 3 months later. Conclusions: Discontinuation of CR influenced standing balance and limb muscle mass. While the restart of CR may improve a patient's balance, more time is required for additional daily physical activities. The recent pandemic-related interruption of CR should inspire the development of alternatives that could ensure the continuity of CR in a future crisis.

Depression and Anxiety Are Associated with Physical Performance in Patients Undergoing Cardiac Rehabilitation: A Retrospective Observational Study.

BACKGROUND: Cardiac rehabilitation (CR) combined with stress management training has been shown to be associated with fewer clinical events than CR alone. However, there have been no reports on the associations of CR with the psychological condition and detailed physical activities evaluated on the same day. METHOD: One hundred outpatients who participated in a CR program were graded on the hospital anxiety and depression scale (HADS). We divided them into a high HADS group (n = 32) and a normal HADS group (n = 68) and investigated by whole patients, ischemic heart disease (IHD) patients, and heart failure patients. RESULTS: Overall, the patient age was 70.5 ± 9.6 years, the percentage of males was 73.0%, and the body mass index was 23.4 (21.7-26.0) kg/m2. In the high HADS group, overall functional mobility was poor and the distance in a two-minute walking test was short. Especially in IHD patients, the high HADS group showed high fat mass in body composition and low exercise tolerance and ventilator equivalents in cardiopulmonary exercise test. CONCLUSIONS: Depression and anxiety involved poor physical performance in CR outpatients and particularly involved low exercise tolerance in IHD patients. To evaluate accurate physical performance, it is necessary to investigate psychological condition.

The moderate-intensity continuous exercise maintains renal blood flow and does not impair the renal function.

Exercise is restricted for individuals with reduced renal function because exercising reduces blood flow to the kidneys. Safe and effective exercise programs for individuals with reduced renal function have not yet been developed. We previously examined the relationship between exercise intensity and renal blood flow (RBF), revealing that moderate-intensity exercise did not reduce RBF. Determining the effects of exercise duration on RBF may have valuable clinical applications. The current study examined the effects of a single bout of continuous exercise at lactate threshold (LT) intensity on renal hemodynamics. Eight adult males participated in this study. Participants underwent 30 min of aerobic exercise at LT intensity using a cycle ergometer. Evaluation of renal hemodynamics was performed before and after exercise, in the recovery phase using ultrasound echo. Furthermore, blood and urine samplings were conducted before and after exercise, in the recovery phase. Compared with resting, RBF was not significantly changed immediately after continuous exercise (319 ± 102 vs. 308 ± 79 ml/min; p = 0.976) and exhibited no significant changes in the recovery phase. Moreover, urinary kidney injury molecule-1 (uKIM-1) level exhibited no significant change immediately after continuous exercise (0.52 ± 0.20 vs. 0.46 ± 0.27 µg/g creatinine; p = 0.447). In addition, the results revealed no significant change in urinary uKIM-1 in 60-min after exercise. Other renal injury biomarkers exhibited a similar pattern. These findings indicate that a single bout of moderate-intensity continuous exercise maintains RBF and does not induce renal injury.

Difference in Prognosis between Continuation and Discontinuation of A 5-Month Cardiac Rehabilitation Program in Outpatients with Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Cardiac rehabilitation (CR) is a requisite component of care for patients with heart failure (HF). We aimed to evaluate the clinical outcomes in outpatients with HF with preserved ejection fraction (HFpEF) compared to those in patients with non-HFpEF who did and did not continue a 5-month CR program. METHODS: 173 outpatients with HF who participated in a 5-month CR program were registered. We divided them into two groups: HFpEF (n = 84, EF 63 ± 7%) and non-HFpEF (n = 89, EF 31 ± 11%). We further divided the patients into those who continued the CR program (continued group) and those who did not (discontinued group) in the HFpEF and non-HFpEF groups. The clinical outcomes at 5 months were compared among the groups. RESULTS: There were no significant differences in patient characteristics at baseline between the continued and discontinued groups in the HFpEF and non-HFpEF groups except for % diabetes mellitus in the non-HFpEF group. The rates of all-cause death and hospital admissions in the continued group in both the HFpEF and non-HFpEF groups were significantly lower than those in the discontinued group. The all-cause death and hospital admissions in each group were independently associated with the continuation of the CR program. CONCLUSIONS: The continuation of a 5-month CR program was associated with the prevention of all-cause death and hospital admissions in both the HFpEF and non-HFpEF groups.

Possibility of Cardio-renal Protection by Long-term Cardiac Rehabilitation in Elderly Patients with Cardiovascular Diseases.

Objective Cardiac rehabilitation (CR) improves the mortality in patients with cardiovascular disease (CVD). Even in elderly patients with CVD, CR may improve the activities of daily living (ADL). Methods Eighty-eight outpatients over 65 years of age at the beginning of a CR program (baseline) at Fukuoka University Hospital who had CVD and could be followed-up for up to 5 years were enrolled. CVD included ischemic heart disease, postoperative valvular heart disease, dissecting aneurysm of the aorta and peripheral artery disease. The patients were divided into 2 groups according to the average estimated glomerular filtration rate (eGFR) at baseline (55.4±14.8 mL/min/1.73 m2): high (≥55.4, n=44) and low (<55.4, n=44)-eGFR groups. The anaerobic threshold (AT) during exercise and left ventricular ejection fraction (LVEF) were measured by cardiopulmonary exercise (CPX) and ultrasound cardiography, respectively. The serum brain natriuretic protein (BNP) was also measured every year. Results The average age at baseline in all patients was 73±6 years. In all patients, the level of eGFR did not significantly change for 5 years (55±15 mL/min/1.73 m2 at baseline vs. 48±14 at the end of the study). The AT (3.7±1.0 METs at baseline vs. 3.3±0.5), LVEF (57±13% vs. 64±10%) and BNP (260±452 pg/mL vs. 308±345) were also maintained for 5 years. In both the low- and high-eGFR groups, the eGFR, AT during exercise, LVEF and BNP at the end of the study were not significantly changed compared to the baseline values, although some changes were observed during the follow-up period. Conclusion Long-term CR in CVD outpatients over 65 years of age helped maintain the AT, LVEF, BNP and eGFR for 5 years. CR afforded cardio-renal protection in elderly patients with CVD.

Differential prognostic impact between completion and non-completion of a 5-month cardiac rehabilitation program in outpatients with cardiovascular diseases.

BACKGROUND: Cardiac rehabilitation (CR) is an essential component of care for patients with cardiovascular diseases (CVD). We aimed to evaluate clinical outcomes in outpatients with CVD who did and did not complete a 5-month CR program. METHODS: Three hundred thirty-two outpatients with CVD who participated in a 5-month CR program and were followed-up for maximum 5 years were registered. We divided the patients into two groups: those who completed the CR program (success group, n = 175) and those who could not (non-success group, n = 157). Both long-term (5 years) and short-term (5 months) clinical outcomes were compared between the two groups. RESULTS: There were no significant differences in patient characteristics at baseline between the success and non-success groups. With regard to both long-term and short-term clinical outcomes, the rates of all-cause death and hospital admission in the success group were significantly lower than those in the non-success group by a Kaplan-Meier analysis. There was a significant difference in short-term CVD death and hospital admission between the groups, but not for long-term CVD death and hospital. In long-term period, all-cause death and hospital admission was independently associated with completion of the CR program in addition to the presence of peripheral artery disease and VE vs. VCO2 slope after adjusting for age, gender, body mass index, types of CVD and medications. CONCLUSIONS: Completion of a 5-month CR program was associated with the prevention of all-cause death and hospital admission, but not CVD death and hospital admission in the long-term, which suggests that we need to reconsider this issue.

The Current Conditions and Lifestyles of Obese University Students.

BACKGROUND: The prevalence of cardiovascular diseases in Japan remains high, and the onset becomes early. Studies on the current conditions and lifestyles of obese university students may support early interventions to achieve lifestyle modification. METHODS AND RESULTS: The results of periodic health examinations in 32,262 first-year university students revealed that 2,036 (6.3%) were obese. We performed a more detailed examination in 221 of these obese students (165 males and 56 females, age 19 ± 1 years) with study agreement from 2014 to 2016. In this study cohort, the percentage of students who exercised regularly was significantly higher among males than females. Body fat in males with well-exercised was lower than that in males with no exercise. In addition, serum level of high-density cholesterol in males with well-exercised was higher. Among females, there were no significant differences in these parameters between exercisers and non-exercisers. Forty-two obese students (40 males and two females) met the diagnostic criteria of metabolic syndrome (MetS). Among males, levels of body fat, uric acid, liver enzyme and insulin resistance in the MetS group were significantly higher than those in the non-MetS group. The average ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) was low (0.14). CONCLUSIONS: Although the proportions of students with obesity and/or MetS were not high, the EPA/AA ratio in obese young males was low, which may be associated with a high risk of coronary atherosclerosis. To prevent the onset of cardiovascular diseases early intervention to achieve lifestyle modification may be important.