Anat Berkovitch

The association between cardiorespiratory fitness and cardiovascular risk may be modulated by known cardiovascular risk factors

BACKGROUND We aimed to evaluate whether reduced cardiovascular fitness has a direct or indirect effect for the development of cardiovascular disease. METHODS We investigated 15,595 men and women who were annually screened in a tertiary medical center. All subjects were free of ischemic heart disease and had completed maximal exercise stress test according to the Bruce protocol at their first visit. Fitness was categorized into age- and sex-specific quintiles (Q) according to Bruce protocol treadmill time with Q1 as lowest fitness. Subjects were categorized at baseline into 3 groups: low fitness (Q1), moderate fitness (Q2-Q4), and high fitness (Q5). The primary end point of the current analysis was the development of a first cardiovascular event during follow-up. RESULTS Mean age of study patients was 48 ± 10 years, and 73% were men. A total of 679 events occurred during 92,092 person-years of follow-up. Kaplan-Meier survival analysis showed that the cumulative probability of cardiovascular events at 6 years was significantly higher among subjects with low fitness (P < .001). Low fitness was associated with known cardiovascular risk factors, including hypercholesterolemia (odds ratio [OR] 1.58, 95% CI 1.31-1.89), diabetes mellitus (OR 2.32, 95% CI 1.58-3.41), and obesity (OR 10.46, 95% CI 8.43-12.98). The effect of low fitness on cardiovascular events was no longer significant when including diabetes mellitus, hypercholesterolemia, and obesity as mediators (hazard ratio 0.99, 95% CI 0.82-1.19). CONCLUSIONS The association between cardiovascular fitness and adverse cardiovascular outcomes may be modulated through traditional cardiovascular risk factors. These findings need to be further validated in prospective clinical trials.

The association between normal-range admission potassium levels in Israeli patients with acute coronary syndrome and early and late outcomes

AbstractAbnormal serum potassium levels are associated with an increased risk of ventricular arrhythmias and mortality in patients with acute myocardial infarction (AMI). The aim of the present study was to evaluate whether different levels of serum potassium, within the normal range, are associated with worse outcomes. The present study comprised 1277 patients with AMI and normal-range admission potassium levels (3.5–5.2 mEq/L), who were enrolled and prospectively followed up in the Acute Coronary Syndrome Israeli Survey between 2010 and 2013. Patients were divided into 4 quartiles based on admission potassium levels; “normal-low” (K ≥ 3.5 and K ⩽ 3.9), “normal-moderate” (K > 3.9 and K ⩽ 4.18), “normal-high” (K > 4.18 and K ⩽ 4.45), and “normal-very high” (K > 4.45 and K ⩽ 5.2). We analyzed the association between admission serum potassium levels and 7 days in-hospital complication rates, and 30-day and 1-year all-cause mortality rates. Patients with “normal-very high” potassium displayed increased frequency of baseline clinical risk factors and experienced a higher rate of acute kidney injury during hospitalization compared with the “normal-low” group (7.7% vs 2.4%; P = 0.002). However, the rate of in-hospital ventricular arrhythmias was similar across the range of admission potassium levels (overall P = 0.26), Multivariate analysis showed that compared with “low-normal” potassium values, patients with “normal-very high” potassium levels experienced increased risk for 30-days (adjusted hazard ratio 2.88, 95% confidence interval 1.05–7.87, P = 0.039) and 1-year all-cause mortality (adjusted hazard ratio 1.98, 95% confidence interval 1.05–3.75, P = 0.034). In patients admitted with AMI, admission serum potassium levels of 4.45 to 5.2 mEq/L are not associated with in-hospital ventricular arrhythmias, but are associated with increased short and long-term mortality.

Use of exercise capacity to improve SCORE risk prediction model in asymptomatic adults

AIMS The SCORE risk estimation system is used for cardiovascular risk stratification in apparently healthy adults and is based on known cardiovascular risk factors. The purpose of the current study was to evaluate whether exercise capacity can improve the accuracy of the SCORE overall survival risk estimation. METHODS AND RESULTS We investigated 22 878 asymptomatic men and women who were annually screened in a tertiary medical centre. All subjects were free of known ischaemic heart disease, and had completed maximal exercise stress test according to the Bruce protocol. The SCORE risk estimation system was used to evaluate individual cardiovascular risk for all subjects. The primary endpoint was mortality, after exclusion of patients with metastatic cancer during follow-up. The incremental contribution of exercise capacity in predicting the risk of death was evaluated by net reclassification improvement (NRI) and area under the receiver operating curve (AUROC). Mean age of the study population was 47.4 ± 10.3, and 71.6% were men. There were 505 (2.21%) deaths during a mean follow-up of 9.2 ± 4.1 years. Kaplan-Meier survival analysis showed that both SCORE and low exercise capacity were associated with reduced survival. When added to the SCORE risk prediction, exercise capacity allowed more accurate risk stratification: NRI analysis showed an overall improvement of 56.8% in the accuracy of classification and the AUROC increased (0.782 vs. 0.766). CONCLUSION Both SCORE and exercise capacity are strong independent predictors of all-cause mortality. The addition of exercise capacity to the SCORE risk model can improve the accuracy of the model.

Time dependent changes in high density lipoprotein cholesterol and cardiovascular risk

BACKGROUND High-density lipoprotein cholesterol (HDL-C) is a strong inverse predictor of cardiovascular events. The aim of the current study was to evaluate the correlation between changes in HDL-C and subsequent cardiovascular events. METHODS Study population comprised 13,037 subjects free of cardiovascular disease with a mean follow up of 6 ± 3 years. Low HDL-C was defined as < 40 mg/dl for men and <50mg/dl for women. Participants were divided into three groups based on HDL-C levels at the first and second baseline visits: persistently-low HDL-C (LL); persistently-high HDL-C (HH); and those with high HDL-C in a one visit only: intermittently high HDL-C (LH/HL). The primary endpoint was the first occurrence of a cardiovascular event. RESULTS A total of 529 (4.1%) incident events occurred during follow-up. HDL-C levels increased significantly between the two landmark visits (47.5 ± 12.6 vs. 48.1 ± 12.2, p<0.001). Kaplan-Meier survival analysis showed that the cumulative probability of cardiovascular events at 6 years was highest among subjects in the LL group (7.6%), and similar among LH/HL and HH groups (3.3% and 4%, respectively; log-rank p=0.001). Multivariate Cox regression analysis, with HDL-C as time-dependent covariate, showed that subjects with persistently low HDL-C during follow up experienced a 51% increased cardiovascular risk compared with subjects with persistently high HDL-C (p=0.026). Subjects with intermittently high HDL-C during follow up experienced similar risk to those with persistently high HDL-C (HR=1.02; p=0.89). CONCLUSIONS Variations in HDL-C levels during follow-up are associated with subsequent cardiovascular risk. Patients who retain low HDL-C levels are at the cardiovascular highest risk.

Time-dependent relation between smoking cessation and improved exercise tolerance in apparently healthy middle-age men and women

Background Smoking is an independent cardiovascular risk factor and correlates with reduced exercise tolerance. However, data on the time dependent effect of smoking cessation on exercise tolerance are limited. Design and methods We investigated 17,115 men and women who were annually screened at the Institute for Medical Screening of the Chaim Sheba Medical Centre. All subjects had their smoking status documented and performed an exercise stress testing (EST) according to Bruce protocol at each visit. Subjects were divided at baseline into four groups: active smokers (N = 2858), recent quitters (smoking cessation ≤2 years before baseline EST; N = 861), remote quitters (smoking cessation >2 years before the baseline EST; N = 3856) and never smokers (N = 9810). Baseline and follow up EST duration were compared among the four groups. Results Recent quitters demonstrated a 2.4-fold improvement in their EST duration compared with active smokers (improvement of 24 ± 157 vs. 10 ± 157 s, respectively, p = 0.02). Multivariate logistic regression showed that recent quitters were 26% more likely to improve their exercise tolerance compared with active smokers (95% confidence interval (CI) 1.08–1.47, p = 0.003). Assessing smoking status as a time-dependent covariate during four consecutive visits demonstrated that recent quitters were 17% more likely to improve their exercise tolerance compared with active smokers (95% CI 1.02–1.34, p = 0.02), with a less pronounced benefit among remote quitters (hazard ratio = 1.11, 95% CI 1.02–1.21; p = 0.01). Conclusions Smoking cessation is independently associated with improved exercise tolerance. The benefits of smoking cessation are evident within the first two years of abstinence.

Poor Heart Rate Recovery Is Associated With the Development of New-Onset Atrial Fibrillation in Middle-Aged Adults

OBJECTIVE To investigate the association between heart rate recovery (HRR) and new-onset atrial fibrillation (AF) in middle-aged adults. PATIENTS AND METHODS Heart rate recovery was calculated using the exercise stress test in 15,729 apparently healthy self-referred men and women who attended periodic health screening examinations between January 2000, and December 2015. All participants completed the maximal exercise stress test according to the Bruce protocol and were followed clinically on a yearly basis for a median of 6.4±4 years. The primary end point was new-onset AF. Participants were grouped according to HRR at 5 minutes, dichotomized at the median value (<73 beats/min). RESULTS Participants with low HRR were older, were more commonly men, had a higher rate of comorbidities, and were less fit. Kaplan-Meier survival analysis revealed that the cumulative probability of AF at 6 years was higher in participants with low HRR (2.1%) than in those with high HRR (0.6%) (log-rank, P<.001). Older age, male sex, obesity resting heart rate, and ischemic heart disease were all associated with increased AF risk in a univariate Cox regression model (P<.05 for all). Multivariate Cox regression analysis revealed that low HRR was independently associated with increased AF risk (hazard ratio, 1.92; 95% CI, 1.3-2.8; P<.001) after adjustment for multiple confounders. CONCLUSION Lower HRR is independently associated with the development of new-onset AF during long-term follow-up in middle-aged adults.

Precipitating Factors for Acute Heart Failure Hospitalization and Long-term Survival

AbstractHeart failure (HF) patients have frequent exacerbations leading to high consumption of medical services and recurrent hospitalizations.Different precipitating factors have various effects on long-term survival.We investigated 2212 patients hospitalized with a diagnosis of either acute HF or acute exacerbation of chronic HF. Patients were divided into 2 primary precipitant groups: ischemic (N = 979 [46%]) and nonischemic (N = 1233 [54%]). The primary endpoint was all-cause mortality.Multivariate analysis demonstrated that the presence of a nonischemic precipitant was associated with a favorable in-hospital outcome (OR 0.64; CI 0.43–0.94), but with a significant increase in the risk of 10-year mortality (HR 1.12; CI 1.01–1.21). Consistently, the cumulative probability of 10-year mortality was significantly higher among patients with a nonischemic versus ischemic precipitant (83% vs 90%, respectively; Log-rank P value <0.001). Subgroup analysis showed that among the nonischemic precipitant, the presence of renal dysfunction and infection were both associated with poor short-term outcomes (OR 1.56, [P < 0.001] and OR 1.35 [P < 0.001], respectively), as well as long-term (HR 1.59 [P < 0.001] and HR 1.24 [P < 0.001], respectively).Identification of precipitating factors for acute HF hospitalization has important short- and long-term implications that can be used for improved risk stratification and management.

Long-Term Outcomes of Iliofemoral Artery Stents after Transfemoral Aortic Valve Replacement

PURPOSE To report long-term results of iliofemoral stent placement after transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS TAVR access-related complications treated with iliofemoral stent placement were recorded in 56 patients (mean age, 81 years; range; 53-93 years; 48% male) of 648 patients who underwent TAVR at a single center. Fifty-six patients treated with stent placement (40 patients with stent grafts and 16 patients with bare metal stents) underwent clinical and ultrasonographic follow-up after a mean of 676 days (range, 60-1840 days). RESULTS During follow-up, none of the 56 patients who had stent placement underwent a vascular reintervention of the affected limb, and none suffered from limb claudication. No decrease was observed in ankle-brachial index (ABI) values to an abnormal value, except in 1 patient (mean preprocedural and postprocedural ABI of 1.2 ± 0.14, range, 0.97-1.4 and 1.19 ± 0.24, range, 0.65-1.54, respectively). Arterial duplex assessment showed normal stent flow velocity (mean, 168.7 ± 63.2 cm/sec; range, 80-345 cm/sec) in all but 1 patient. CONCLUSION Iliofemoral stent implantation is a safe and efficacious treatment for vascular access site and access-related complications during transfemoral TAVR.

The Effect of Head and Neck Radiotherapy on Blood Pressure and Orthostatic Hypotension in Patients With Head and Neck Tumors

BACKGROUND Radiotherapy (RT) plays a key role in the management of head and neck cancer (HNC), especially in locally advanced disease. Patients undergoing head and neck RT, especially elderly ones, are suffering from low and labile blood pressure (BP) during the treatment. They complain of weakness and fatigue and are prone to recurrent falls. The aim of this study was to characterize BP changes during RT period. METHODS Patients with HNC, receiving radiation to the neck, were recruited from Sheba medical center RT unit. Office BP, orthostatic measurements, 24-hour ambulatory BP monitoring, body weight, and metabolic parameters were measured at baseline after 30 days and after 90 days from beginning of therapy. RESULTS Nineteen patients (17 males), 64 ± 12 years old were recruited. Nine hypertensive patients continued their antihypertensive treatment during the study. Office systolic BP and diastolic BP decreased significantly after 30 days (128 ± 4/80 ± 3 to 122 ± 3/74 ± 3 mm Hg; P < 0.05). Average 24-hour BP values after 30 days of RT decreased from 130 ± 3/76 ± 2 to 123 ± 3/71 ± 2 mm Hg; P < 0.05. A similar trend was observed for day and night BP levels. Decrease in office and ambulatory BP was sustained for several months after RT completion. No orthostasis was observed during the study period. Patient lost weight significantly during the study period. However, BP changes were independent of weight loss. CONCLUSION There is a significant and sustained BP reduction after head and neck RT, without orthostatic changes. Clinicians should be aware of this phenomenon and consider treatment adaption accordingly.

POOR HEART RATE RESERVE PREDICTS NEW ONSET ATRIAL FIBRILLATION IN MIDDLE AGED ADULTS

Autonomic dysfunction is associated with the atrial arrhythmogenesis. The purpose of this study was to investigate the association between heart rate reserve (HRR), and new onset atrial fibrillation (AF) among middle-aged adults. We investigated 15,729 apparently healthy self-referred men and women