[show abstract][hide abstract] ABSTRACT: Attenuated heart rate (HR) response during exercise is associated with adverse cardiovascular outcome. The acceptable value for HR response is 85% of the age-predicted maximal HR (APMHR). This study hypothesized that mild attenuation of HR response during exercise among healthy subjects is associated with increased cardiovascular risk. The study population comprised 10,323 healthy men and women without known cardiovascular disease (CVD) or diabetes mellitus who underwent a yearly screening program and were followed up during a mean period of 4.3 years. Participants were grouped to 3 tertiles based on the percentage of their APMHR reached at the baseline stress test. The primary end point was the occurrence of CVD or cerebrovascular disease. A total of 1,015 incident cases of CVD occurred during follow-up. A multivariate Cox proportional hazards regression model showed that the CVD risk of subjects who reached 60% to 96% of their APMHR was 35% greater compared with those who reached their APMHR (p = 0.001). A subgroup analysis among subjects who reached 85% of their APMHR showed that even mildly attenuated heart response (in the range of 85% to 96% APMHR) was independently associated with 36% increase in CVD risk (p <0.001). In conclusion, attenuated HR response during exercise is a powerful and independent predictor of adverse cardiovascular events during long-term follow-up among healthy men and women. The prognostic implications of attenuated HR response in this population are apparent even with a minor decrease of the maximal HR to <96% of the APMHR.
The American journal of cardiology 08/2013; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abstract Objective: Previous studies have demonstrated an association between increased serum uric acid (SUA) levels and incident diabetes. Most clinical and epidemiological investigations, however, focused solely on male populations or did not analyze men and women separately. We assessed the association between SUA levels and diabetes incidence in a large cohort of apparently healthy men and women. Methods: Data were retrospectively gathered from 9140 adults who participated in annual medical screening visits during 2000-2009. Mean follow-up time was 4.8 years, and the median age was 50 years. Laboratory test results, data from physical examinations, medical history, and lifestyle information were extracted. The main outcome measure was incident diabetes, defined as two consecutive fasting glucose tests higher than 125 mg/dL. Cox proportional-hazards multivariate models were applied for measuring hazard ratios (HRs) for diabetes according to continuous and categorical levels of uric acid. Results: We identified 499 new cases of diabetes (total, 5.5%: men, 6.2%; women, 3.6%) during the follow-up period. The gender-specific HRs for diabetes, adjusted for age and a set of prespecified multiple risk and protective factors, were 1.57 for each 1 mg/dL increase in SUA (95% confidence interval [CI], 1.32-1.86) in women and 1.08 (95% CI, 0.99-1.17) in men; p for interaction of SUA by gender <0.001. Conclusion: SUA is independently associated with diabetes outcome, considerably more in women than in men.
Journal of Women s Health 06/2013; · 1.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Clinical thyroid disease is associated with changes in the cardiovascular system, including changes in heart rate during exercise. However, data on the relation between subclinical thyroid disease (SCTD) and heart rate during exercise are limited. Methods: We investigated 3,799 apparently healthy subjects who were evaluated in the Institute for Preventive Medicine at the Sheba Medical Center. All subjects answered standard health questionnaires, were examined by a physician, completed routine blood tests including TSH, free T3 and free T4 levels, and underwent a treadmill exercise according to the Bruce protocol. Subjects with known thyroid disease or those who were taking thyroid related drugs were excluded from the analysis. Heart rate profile was compared between patients with subclinical hypothyroidism (SCHypoT), normal thyroid functions and patients with subclinical hyperthyroidism (SCHyperT) using propensity score matching. Results: Seventy patients had SCHyperT and 273 had SCHypoT. Compared with age and gender matched normal subjects, SCHyperT subjects had higher resting heart rate (83±17 vs. 76±12 beats per minute [bpm], p=0.006), significantly higher recovery heart rate (94±12 vs. 90±12 bpm, P=0.045) and a significantly lower heart rate reserve (80±20 vs. 87±18 bpm, P=0.006). Subjects with SCHypoT showed a trend toward a lower resting heart rate (75±13 vs. 77±15 bpm, P=0.09) and had a significantly lower recovery heart rate (88±12 vs. 90±13 bpm, P=0.035). There was no significant difference in exercise duration between subjects with SCTD and their matched normal controls. Conclusions: Subjects with subclinical thyroid disease have significantly different heart rate profile during rest, exercise and recovery.
Thyroid: official journal of the American Thyroid Association 06/2013; · 2.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
While moderate and severe chronic kidney disease is an established independent risk factor for cardiovascular disease (CVD), the association of estimated glomerular filtration rate (eGFR) differences within the normal to mildly reduced range (from 60 to >90 ml/min/1.73 m(2)) and CVD is less clear. Our aim was to examine the association of eGFR with incident CVD in a cohort of predominantly healthy subjects with normal to mildly reduced renal function.DesignRetrospective cohort study.Methods
We collected demographic, clinical, and laboratory parameters of subjects free of diabetes mellitus or CVD who attended annual medical screening examinations between 2001 and 2009. Main outcome measures were a new diagnosis of coronary artery disease (CAD) or cerebrovascular events (CVE).ResultsDuring a median follow up of 4.3 years, among 10,909 subjects (mean eGFR 78.5 ± 12.2 ml/min/1.73 m(2)), 10.3% were diagnosed with CAD (n = 1025) or CVE (n = 94). Compared with subjects in the highest eGFR quintile (≥88.8 ml/min/1.73 m(2)), subjects in the lowest quintile (≤68.2 ml/min/1.73 m(2)) had a hazard ratio (HR) of 1.64 (95% CI 1.35-2.00; p < 0.001) for a CAD outcome, but this association was no longer significant after adjustment for age and other confounders (adjusted HR 1.08; p = 0.55). Similar findings were obtained for the association of eGFR with CVE.Conclusions
In a predominantly healthy population with normal to mildly reduced renal function, lower eGFR is associated with higher risk for CVD; however, this association is not independent but merely reflects the association of age and other cardiovascular risk factors with reduced eGFR.
European journal of preventive cardiology. 02/2013;
[show abstract][hide abstract] ABSTRACT: Studies in different populations with high risk for cardiovascular disease (CVD) have shown an association between serum uric acid (SUA) and CVD. However, only a few studies have demonstrated such an association in healthy populations. The aim of this study was to investigate the association between SUA and CVD in a cohort of men and women without diabetes or CVD. A retrospective study was conducted, with a mean 4.8-year follow-up. The outcome was the occurrence of a cardiovascular event, defined as the diagnosis of ischemic heart disease, acute coronary syndrome, acute myocardial infarction, or ischemic stroke. Mean SUA levels were 6.2 ± 1.1 mg/dl for men (n = 6,580) and 4.4 ± 1.1 mg/dl for women (n = 2,559). For women, the rate of CVD occurrence was 11.6% for the highest quartile of SUA level, compared with 5.0% to 6.5% for the lower 3 quartiles. For men, the rate of CVD occurrence was 14.0% for the highest quartile of SUA level, compared with 10.8% for the lowest quartile. The hazard ratio for CVD, adjusted for age, serum creatinine level, body mass index, systolic blood pressure, low-density lipoprotein cholesterol level, triglyceride level, plasma fasting glucose, physical activity, cardiovascular family history, use of diuretics, and current smoking, was 1.24 (95% confidence interval 1.08 to 1.41) for women and 1.06 (95% confidence interval 1.00 to 1.13) for men (p for interaction = 0.04). In conclusion, the strong association of SUA levels with CVD in women, compared with the much lesser degree in men, highlights the necessity of stratifying by gender in investigations of cardiovascular risk factors and supports exploration of SUA as a marker of CVD risk in healthy populations.
The American journal of cardiology 01/2013; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: Body mass index (BMI) is more commonly used than waist circumference as a measure of adiposity in clinical and research settings. The purpose of this study was to compare the associations of BMI and waist circumference with cardiorespiratory fitness. METHODS: In a cross-sectional study of 403 healthy men and women aged 50 +/- 8.8 years, BMI and waist circumference were measured. Cardiorespiratory fitness was assessed from estimated maximal O2 uptake (VO2max), as calculated from a maximal fitness test. RESULTS: Mean BMI (kg/m2) was 27.8 +/- 3.7 and 25.5 +/- 4.6; and mean waist circumference (cm) 94.1 +/- 9.7 and 84.3 +/- 10.4 for men and women, respectively. Both men and women reported an average of 2.5 hours of weekly sports related physical activity, and 18% were current smokers. Correlation coefficients between both BMI and waist circumference, and VO2max were statistically significant in men (r = -0.280 and r = -0.377, respectively, p > 0.05 for both) and in women (r = -0.514 and r = -0.491, respectively, p > 0.05 for both). In women, the contribution of BMI to the level of VO2max in a regression model was greater, while in men waist circumference contributed more to the final model. In these models, age, hours of training per week, and weekly caloric expenditure in sport activity, significantly associated with VO2max, while smoking did not. CONCLUSION: The differences observed between the sexes in the associations of BMI and waist circumference with VO2max support the clinical use of both obesity measures for assessment of cardiorespiratory fitness.
[show abstract][hide abstract] ABSTRACT: Serum lactate dehydrogenase (LDH) is known pathologic marker for a diversity of diseases, including myocardial ischemia. Strenuous and enduring physical activity can transiently induce a greater total LDH level, still within its normal range. To date, however, it has not been determined whether normal-range LDH might be inversely associated with coronary artery disease (CAD) in the low-cardiovascular-risk, physically active, adult population. We conducted a retrospective cohort analysis. A total of 5,519 healthy adults aged 34 to 86 years were followed up for a mean period of 4.2 years. The cohort incidence of CAD was 6.1% (338 cases) from 2001 to 2009. In the present cohort, greater mean LDH levels were significantly associated with a greater number of years, days/week, and minutes/week of leisure time activity (p = 0.02, p = 0.04, and p = 0.01, respectively). These associations were externally validated successfully by analysis of all 5,064 healthy participants aged ≥40 years with normal-range LDH from the 2007 to 2010 National Health and Nutrition Examination Surveys combined. For instance, the mean LDH level was significantly greater in those engaged in 6 to 7 versus 1 to 5 days/wk of vigorous-intensity work activity (138.0 ± 20.7 IU/L vs 133.3 ± 21.7 IU/L, respectively, p = 0.007). In our cohort, the hazard ratio for CAD according to the normal total serum LDH tertiles, adjusted for multiple risk and protective CAD factors in a Cox proportional hazards model, was 0.70 (95% confidence interval 0.54 to 0.92) in the greater versus lower tertile (p for trend = 0.01). In conclusion, we suggest that increased normal-range total serum LDH is associated with reduced short-term risk of CAD outcome in this low-risk, physically active population.
The American journal of cardiology 09/2012; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Introduction: Colonic diverticulosis is a common condition with obscure pathogenesis. Obesity, hyperlipidemia and hypertension have been demonstrated to increase the risk of complicated diverticular disease, but the impact of metabolic risk factors on the prevalence of uncomplicated diverticulosis has not been clearly determined. Aims: The aim of the study was to examine the impact of obesity and metabolic syndrome on the prevalence of colonic diverticulosis. Methods: This retrospective case-control study included patients aged 40-85 years who were followed up by the Institute of Medical Screening in Israel and underwent colonoscopy in 2006-2011 for indication of colorectal cancer screening. Patients with diverticulosis as detected by colonoscopy were compared to patients without diverticulosis. The comparison parameters included medical history, biometric parameters, biochemical and lipid profile. Results: The study included 3,175 patients. Diverticulosis was diagnosed in 17.4% of the cohort. On univariate analysis, age, male gender, BMI (continuous variable), obesity, systolic blood pressure, low-density lipoprotein cholesterol level, history of hypertension, ischemic heart disease, hypothyroidism, and absence of diabetes mellitus were associated with an increased risk of colonic diverticulosis. On multivariate analysis, advanced age, male gender, obesity (BMI >30), history of hypothyroidism and absence of diabetes mellitus were associated with an increased risk of diverticulosis. Prevalence of colonic polyps was similar in patients with and without diverticulosis. Conclusion: Colonic diverticulosis was associated with age, male gender, obesity and hypothyroidism. Diabetes mellitus was associated with a decreased risk of colonic diverticulosis.
[show abstract][hide abstract] ABSTRACT: High values of resting heart rate were found to be correlated with adverse outcomes in various patient groups. Heart rate variability (HRV) is a reliable technique in determining autonomic nervous system function. Our aim was to evaluate whether a 10-second resting heart rate obtained from a resting electrocardiogram (ECG), could be used as a reliable evaluation of short-term HRV.
Seventy-nine healthy volunteers were included in the study. All participants underwent a 10-second ECG, and 5-minute HRV measurement under strict criteria.
A significantly negative correlation was found between resting heart rate and 5-minute max-RR, min-RR, standard deviation of normal RR intervals (SDNN), root mean square of successive differences of RR intervals (RMSSD), HRV triangular index, number of intervals differing by 50 milliseconds from the preceding interval (NN50), pNN50, standard deviation of the points perpendicular to the line of identity (SD1), standard deviation along the line of identity (SD2), and high frequency spectral component (HF). A significant positive correlation was found between resting heart rate and a 5-minute low frequency spectral component (LF) and LF/HF ratio. Specifically, max-RR and min-RR were found to have the best correlation with resting heart rate.
Resting heart rate obtained from a 10-second ECG can be used for crude estimation of all HRV results in healthy individuals who do not take medications, with variable efficacy depending on the measured parameter. Resting heart rate was especially efficient in predicting max-RR and min-RR. Further research should focus on assessing the reliability of a resting heart rate for HRV evaluation, in patients with autonomic dysfunction and high-risk cardiac patients.
Pacing and Clinical Electrophysiology 07/2011; 34(11):1498-502. · 1.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: Heart rate variability (HRV) is an accepted and reliable means for assessing autonomic nervous system dysfunction. A 5-minute measurement of HRV is considered methodologically adequate. Several studies have attempted to use shorter recordings of 1-2 minutes or 10 seconds. The aim of this study was to determine the reliability of HRV parameters calculated from ultra-short electrocardiogram recordings.
Seventy healthy volunteers were recruited for the study. HRV was evaluated for 5 minutes according to accepted procedures. Thereafter, HRV parameters were recalculated from randomly selected 1-minute and 10-second intervals. The standard and ultra-short measurements were correlated using intraclass correlation coefficients.
Good correlations between the 5-minute electrocardiograms (ECGs) and both the 1-minute and 10-second ECGs were noted for average RR interval, and root mean square of successive differences in RR intervals (RMSSD). No correlation was noted for standard deviation of the RR interval (SDNN) and several other HRV parameters.
RMSSD, but not SDNN, seem a reliable parameter for assessing HRV from ultra-short (1 minute or 10 seconds) resting electrocardiographic recordings. Power spectral analysis and evaluation of other HRV parameters require longer recording periods. Further research is required to evaluate the importance of ultra-short RMSSD for cardiovascular risk stratification.
Annals of Noninvasive Electrocardiology 04/2011; 16(2):117-22. · 1.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: High levels of plasma homocysteine constitute a risk for cardiovascular disease. Physical activity, known to reduce CVD risk, has been related to levels of Hcy. Recently, higher Hcy was shown to be associated with lower cardiovascular fitness in women but not in men.
To further explore the relationship between cardiorespiratory fitness and plasma total homocysteine levels in a large cohort of adult males and females.
This cross-sectional study included 2576 fitness and Hcy examinations in adults (62% males) aged 30-59 years randomly drawn from a population undergoing a periodic health examination in the Sheba Medical Center's Executive Screening Survey. Blood tests were collected for tHcy and a sub-maximal exercise test was performed to estimate cardiorespiratory fitness. Information on CVD/CVD risk factors (coronary heart disease, cerebrovascular accident, diabetes, hypertension or dyslipidemia) was self-reported.
Mean tHcy plasma levels were 14.4 +/- 7.7 and 10.2 +/- 3.0 micromol/ml, and mean maximal oxygen uptake 36.5 +/- 11.7 and 292 +/- 9.5 ml/kg/min for males and females, respectively. A multiple regression analysis, adjusting for age, body mass index and CVD/CVD risk factors, showed no association between cardiorespiratory fitness and level of tHcy in males (P = 0.09) or in females (P = 0.62).
In this sample no association was found between level of cardiorespiratory fitness and plasma tHcy in men or women. The inconsistency of findings and the small number of studies warrant further research of the association between cardiorespiratory fitness and tHcy, an association that may have clinical implications for the modifications of cardiovascular risk factors.
The Israel Medical Association journal: IMAJ 03/2009; 11(2):78-82. · 0.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Epidemiological study and laboratory evidence show that physical activity protects against the development and progression of chronic diseases. The physiological and biomechanical principles of the assessment of physical activity are ambiguous, energy expenditure calculations are complex, and numerous difficulties can be encountered in developing simple field techniques for assessing habitual activity. The greatest obstacle to validating field methods of assessing habitual physical activity or energy expenditure in humans has been the lack of adequate comparison criteria for the technique. Physical activity can be described as having four dimensions: duration (minutes/hours), frequency (time per week/per month), intensity (rate of energy expenditure) and circumstances or purpose of the activity. Methodology incorporating questionnaires/interviews are relatively inexpensive, and at present are the only methods feasible for large population studies. Specific activities can be identified in conjunction with frequency and duration. The procedure does not influence subjects' activities to the extent that can occur with observation or diary keeping. The limitations of questionnaires/interviews are the actual definitions and interpretations of the term "physical activity", despite the attempts of interviewers to provide a clear definition. Subjects do not necessarily recall their activities accurately; they may tend to overestimate time or intensity. A self-administered questionnaire must be suited to respondents' ages and education levels. Detailed questionnaires/interviews place a considerable burden on subjects.
[show abstract][hide abstract] ABSTRACT: The physical activity questionnaire is typically chosen for population studies because it is practical and does not interfere with the behavior of the surveyed individual. This instrument can be adapted for the particular studied population, and in terms of accuracy it is both reliable and valid.
To develop a valid and appropriate measure to assess physical fitness according to the level of physical activity throughout the day, and to estimate the relation between a subjective questionnaire measurement evaluating physical activity, to predicted VO2max, as an objective measure of physical fitness.
Three hundred healthy subjects, 150 men and 150 women, aged 25-65 years old participated in this study. All subjects were routinely examined in the Sheba Medical Center Executive Screening Survey. They were asked to complete a self-administered questionnaire and report on the level of physical activity at work, the level of sports activity and the level of leisure time non-sport activity. The index calculated from the questionnaire was compared to the result from a sub-maximal exercise test, which they performed in The Executive Screening Survey, to composite a valid questionnaire to estimate physical fitness.
A high and statistically significant correlation (r = 0.64, P < 0.01) was found between the indexes of physical activity calculated from the questionnaire to the predicted VO2max, measured from the sub-maximal exercise test. The reliability of the questionnaire was examined by test-retest and a high and statistically significant correlation (r = 0.89, P < 0.01) was found between the first and the proceeding one month administration of the questionnaire. The final modal to predict VO2max included a total index of physical activity, gender, BMI, age and resting heart rate. Overall this model predicted 58% of the VO2max.
The self-administered questionnaire developed in this study has high construct validity and a significant correlation to predicted VO2max, with high sensitivity in both sexes and among active and non-active subjects. It is therefore an appropriate tool to be used in epidemiological studies.
[show abstract][hide abstract] ABSTRACT: Evidence linking cardiovascular risk factors to aortic valve sclerosis (AVS) has led to the assumption that the latter is an atherosclerosis-like process. However, triglyceride (TG)-rich lipoproteins, an important risk factor for atherosclerosis, have been rarely investigated in connection with AVS.
A cross-sectional study of 246 healthy individuals (mean age 59+/-6 years, 77% men) was conducted. Subjects underwent an echocardiographic assessment and extensive blood lipid measurements, including evaluation of TG-related indices, such as serum apolipoprotein (apo) C(II) and C(III) levels, apo C(III) levels in VLDL+LDL particles, and apo C(III) ratio (C(III) level in HDL/C(III) level in VLDL+LDL).
Twenty-three patients (9.3%) were diagnosed as having AVS. On average, these patients were 5 years older and had higher levels of serum cholesterol, LDL-C and LP(a), compared with non-AVS subjects. In addition, the AVS patients exhibited higher concentrations of serum apo C(II), serum apo C(III) and apo C(III) in VLDL+LDL, and a lower apo C(III) ratio. Adjusting for age and gender, a 1 S.D. increment in apo C(III) in VLDL+LDL was associated with odds ratio (OR) of 1.76 (95% CI: 1.17-2.65) for AVS. Further adjustment for atherosclerotic risk factors did not alter the association appreciably (OR=1.65, 95% CI: 1.06-2.58).
TG-rich lipoproteins may be involved in the early development of AVS. Confirmation in prospective studies is required.
[show abstract][hide abstract] ABSTRACT: Triglycerides (TG) are carried in the circulation by diverse lipoprotein particles, which vary in their lipid and protein content, metabolism, and atherogenicity. Several indices related to apolipoproteins (apo) CII and CIII blood concentration have been proposed to reflect TG metabolism more accurately than the blood level of TG. In the present study we compared the distribution of those indices in coronary heart disease (CHD) patients and controls..
Ninety consecutively discharged patients with CHD and 209 healthy controls were included in the analysis. Demographic, clinical, and laboratory characteristics were obtained.
The CHD patients differed appreciably from controls in several TG-related variables. After adjusting for cardiovascular risk factors, significant associations were found between CHD and the following: TG, VLDL-C, apo CIII, apo CIII in HDL, apo CIII in VLDL + LDL, apo CII- to- TG ratio, and apo CIII ratio (CIII in HDL/CIII in VLDL + LDL). Further adjustment for HDL-C substantially attenuated the above associations, except for those regarding apo CIII in VLDL + LDL (odds ratio (OR): 1.69 per 1 SD increment, 95%CI: 1.03-2.77) and apo CIII ratio (OR: 0.40 per 1 SD increment, 95%CI: 0.15-1.00).
Our results add to the growing evidence which links apo CIII concentration in VLDL + LDL to CHD. Further confirmation in prospective studies would be required before considering this measurement as a screening tool.
Preventive Medicine 08/2003; 37(1):18-22. · 3.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Evidence linking cardiovascular risk factors to aortic valve sclerosis (AVS) has led to the assumption that the latter is an atherosclerosis-like process. However, triglyceride (TG)-rich lipoproteins, an important risk factor for atherosclerosis, have been rarely investigated in connection with AVS. Methods: A cross-sectional study of 246 healthy individuals (mean age 59±6 years, 77% men) was conducted. Subjects underwent an echocardiographic assessment and extensive blood lipid measurements, including evaluation of TG-related indices, such as serum apolipoprotein (apo) CII and CIII levels, apo CIII levels in VLDL+LDL particles, and apo CIII ratio (CIII level in HDL/CIII level in VLDL+LDL). Results: Twenty-three patients (9.3%) were diagnosed as having AVS. On average, these patients were 5 years older and had higher levels of serum cholesterol, LDL-C and LP(a), compared with non-AVS subjects. In addition, the AVS patients exhibited higher concentrations of serum apo CII, serum apo CIII and apo CIII in VLDL+LDL, and a lower apo CIII ratio. Adjusting for age and gender, a 1 S.D. increment in apo CIII in VLDL+LDL was associated with odds ratio (OR) of 1.76 (95% CI: 1.17–2.65) for AVS. Further adjustment for atherosclerotic risk factors did not alter the association appreciably (OR=1.65, 95% CI: 1.06–2.58). Conclusion: TG-rich lipoproteins may be involved in the early development of AVS. Confirmation in prospective studies is required.