A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

Diet Quality and Incident Frailty in Adults 65 Years or Older: The Israeli Longitudinal Study on Aging.

OBJECTIVE: To prospectively examine the association between diet quality and frailty incidence in the oldest-old age group. METHODS: We studied an older adult (65+ years) cohort participating in the Israeli National Health and Nutrition Survey of Older Adults in 2005-2006 (T1 [N=1799]). Survivors of T1 were contacted, and between 2017 and 2019, an extensive interview and a functional assessment were conducted (T2) of 604 past participants. A 24-hour dietary recall, assessed at T1, was used to calculate the Healthy Eating Index (HEI-2015) score. A frailty index based on an accumulation of deficits, including clinical, functional, and cognitive measures, was computed. Frail participants at T1 were excluded from the analysis. Logistic regression models were constructed to assess the association of HEI-2015 score with frailty incidence. Inverse probability weighting was used to minimize selection bias due to attrition. RESULTS: Of the 479 T2 participants analyzed (mean [SD] age, 84 [5] years; 50% women), 225 (46%) were classified as frail. Frail participants were older, were less educated, and had a lower household income and a higher comorbidity burden at baseline than non-frail participants. After adjustment for sociodemographic and lifestyle factors, a higher HEI-2015 score was associated with decreased odds of incident frailty (odds ratio, 0.57 [95% CI, 0.35 to 0.91] for the upper tertile and 0.66 [95% CI, 0.42 to 1.06] for the middle tertile compared with the lower tertile; Ptrend=.02). CONCLUSION: In this cohort study of oldest-old participants, improved diet quality was inversely associated with frailty incidence in a dose-dependent manner.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

Peripheral sensory nerve function, type 2 diabetes and frailty among men with cardiovascular disease.

OBJECTIVE: To investigated the cross-sectional association between peripheral sensory nerve function and frailty among community-dwelling men, and examine whether type 2 diabetes (T2D) modifies this association. METHODS: A sample of 349 men [mean age = 77.1 ± 6.4 years; 37 % with T2D] who previously (1990-1998) participated in the Bezafibrate Infarction Prevention (BIP) trial, underwent assessment of frailty and legs vibratory thresholds (LVT), a measure of peripheral sensory nerve function, as part of the BIP Neurocognitive study during 2011-2013. LVT was assessed using a graduated tuning fork and frailty was assessed using the Fried criteria. An ordered logistic regression model was used to assess the link between LVT and degrees of frailty and to test for effect modification by T2D. RESULTS: Overall, 117 (33.5 %) of patients were non-frail, 134 (38.4 %) pre-frail, and 98 (28.1 %) frail. A significant interaction between LVT and T2D with regard to frailty was found. Among men with T2D, estimated OR (95%CI) for increasing frailty at the 1st, 2nd, and 3rd as compared to the top LVT quartile were 13.5 (3.4-54.3), 5.9 (1.5-23.5), and 4.4 (1.20-16.0), respectively. Among men without T2D, the estimated ORs for increasing frailty in patients at the 1st, 2nd, and 3rd quartiles compared to the top LVT quartile were 2.8 (1.1-7.4), 1.6 (0.6-4.1), and 2.5 (1.0-6.5), respectively. CONCLUSION: Frailty is significantly associated with worsening peripheral sensory nerve function, particularly among men with T2D.

Religiosity Is Associated with Reduced Risk of All-Cause and Coronary Heart Disease Mortality among Jewish Men.

Previous studies have found an inverse association between religiosity and mortality. However, most of these studies were carried out with Christian participants. This longitudinal study aimed to determine whether a composite variable based on self-reported religious education and religious practices is associated with coronary heart disease (CHD) and all-cause mortality in 9237 Jewish men aged 40-65 years at baseline, over a 32-year follow-up. Jewish men were characterized by their degree of religiosity, from the Ultra-Orthodox ("Haredim")-the strictest observers of the Jewish religious rules, and in descending order: religious, traditional, secular, and agnostic. Demographic and physical assessments were made in 1963 with a 32-year follow-up. The results indicate that Haredim participants, in comparison to the agnostic participants, had lower CHD mortality. Hazard ratio (HR) and 95% confidence interval (95% CI)-adjusted by age, cigarette smoking, systolic blood pressure, diabetes, socioeconomic status, BMI, and cholesterol, was: [HR = 0.68 (95% CI 0.58,0.80)] for Haredim; [HR = 0.82 (95% CI 0.69,0.96)] for religious; [HR = 0.85 (95% CI 0.73-1.00)] for traditional; and [HR = 0.92 (95% CI 0.79-01.06) for secular, respectively (p for trend = 0.001). The same pattern was observed for total mortality. This study shows an association between religious practice among men and a decreased rate of CHD and total mortality.

Association of Diet Quality With Longevity and Successful Aging in Israeli Adults 65 Years or Older.

Importance: To our knowledge, the role of overall diet quality in successful aging has not been conclusively demonstrated. Objective: To prospectively examine the association between diet quality and longevity and successful aging in a population-based cohort of older adults. Design, Setting, and Participants: Participants in "Mabat Zahav" (the Israeli National Health and Nutrition Survey of Older Adults), an older adult cohort (aged ≥65 years) consisting of a random sample of 1770 individuals, were recruited from July 2005 to December 2006 (time 1 [T1]). Survivors of T1 were again contacted and asked to participate in a second interview. From May 2017 to June 2019 (time 2 [T2]), an extensive face-to-face interview and a functional assessment were conducted in each participant's home in a subsample of 604 participants from T1, representing 72.7% of 820 surviving individuals who were able to complete interviews and assessments. Exposures: A 24-hour dietary recall, assessed at T1, was used to calculate scores from the 2015 version of the Healthy Eating Index (HEI-2015) (scores range from 0 [worst diet] to 100 [best diet]). Main Outcomes and Measures: Time to death, with follow-up lasting through June 2019, and successful aging. The latter, based on T2 assessment, was defined as (objectively measured) preserved physical and cognitive function and (subjective) mental well-being and favorable self-rated health. Inverse probability weighting was used in the analysis to minimize attrition bias. Results: At T1, the study included 1770 participants (mean [SD] age, 74.6 [6.2] years; 943 women [53%]). On average, participants with higher HEI-2015 scores had healthier lifestyles and higher socioeconomic status at T1. During a median follow-up duration of 12.6 years (IQR, 7.6-13.2 years), 893 deaths occurred. Among the 596 T2 participants analyzed (mean [SD] age, 84.1 [4.4] years; 334 [56%] women), 242 (40%) met successful aging criteria. After adjustment for sociodemographic and lifestyle risk factors, a higher HEI-2015 score was inversely associated with mortality (hazard ratios, 0.85; 95% CI, 0.72-0.99 in the upper tertile and 0.83; 95% CI, 0.71-0.98 in the middle tertile vs the lower tertile; P = .04 for trend) and was positively associated with successful aging (odds ratios, 1.73; 95% CI, 1.10-2.72 in the upper tertile and 1.30; 95% CI, 0.83-2.03 in the middle tertile vs the lower tertile; P = .03 for trend). Conclusions and Relevance: In this cohort study of older adults in Israel, improved diet quality was associated with increased longevity and successful aging in a dose-dependent manner. These data contribute to the body of literature that suggests diet quality is associated with aging in the older age group.

Association of socioeconomic status measures with physical activity and subsequent frailty in older adults.

BACKGROUND: Despite increased recognition, frailty remains a significant public health challenge. OBJECTIVE: we aimed to assess the role of education and income, as well as neighborhood socioeconomic status, on physical activity and subsequent frailty in older adults. METHODS: Using a population-based cohort of older adults, this study examined the relationship between socioeconomic status (SES) factors, physical activity and frailty. The study included 1,799 participants (mean [SD], 74.6 (6.2), 53.3% female) from the "National Health and Nutrition Survey of Older Adults Aged 65 and Over in Israel", conducted in 2005-2006. A follow-up interview was performed 12-14 years later in a subgroup of 601 subjects (mean [SD], age 84[4]; 56% women). Self-reported leisure-time physical activity (LTPA) was measured at both baseline and follow-up. SES measures were assessed at baseline. Frailty was measured at follow-up, using the Fried's Phenotype Model. RESULTS: All SES measures were strongly and positively associated with LTPA (all p < 0.001). Eighty-two participants (14%) were classified as frail at follow-up. After age and sex adjustment and accounting for attrition bias using inverse probability weighting, baseline LTPA (OR = 2.77, 95% CI: 1.57-4.90, for inactivity; OR = 1.41, 95% CI: 0.75-2.68, for insufficient activity, compared with sufficient activity, Ptrend < 0.001) was inversely associated with incident frailty. The association persisted after further adjustment for SES and comorbidity. CONCLUSION: Among older individuals, multiple SES measures were positively associated with LTPA, which was a strong predictor of lower subsequent frailty risk.

Adherence to Mediterranean diet and subsequent cognitive decline in men with cardiovascular disease.

Backgrounds and aims: Evidence from recent years highlighted the importance of the Mediterranean diet for brain health. We investigated the association between adherence to Mediterranean diet and change in cognitive functions two decades later in patients with cardiovascular disease (CVD).Methods: Participants were men with a history of CVD, who previously participated in the Bezafibrate Infarction Prevention (BIP) trial between 1990 and 1997, had a food diary record, and underwent cognitive evaluations 14.6 ± 1.9 years (T1) and 19.9 ± 1.0 years after baseline (T2) as part of the BIP Neurocognitive study (n = 200, mean age at 57.3 ± 6.3 years). Adherence to the Mediterranean diet was determined from the self-administered 4-day food diary record, with patients categorized into high, middle and poor levels of adherence if they received >5, 4-5 and <4 points, respectively. Cognitive function was assessed using the NeuroTrax computerized battery. Linear mixed models were applied.Results: Among the 200 patients, 52 (26%) had poor adherence, 98 (49%) had middle adherence and 50 (25%) had high levels of adherence to the Mediterranean diet. Those categorized to the poor adherence level had poorer cognitive function at T1 compared to the other groups. Additionally, poor vs. high level of adherence was associated with a greater decline in overall cognitive performance [z-score = -0.23 and 95% confidence interval (CI), -0.43;-0.04; p = 0.021] and in visual spatial functions (-0.46 95% CI, -0.86;-0.06; p = 0.023).Conclusion: This study stresses the possible role of the Mediterranean diet in men with a high vascular burden and may set the ground for future intervention to reduce their risk for cognitive decline.

Resumption of sexual activity after acute myocardial infarction and long-term survival.

AIMS: Sexual activity is an important factor in the overall quality of life. We examined whether resumption of sexual activity frequency within the first few months after myocardial infarction (MI) is associated with long-term survival. METHODS AND RESULTS: Sexually active patients aged ≤65 years (n = 495; median age, 53 years), drawn from the longitudinal Israel Study of First Acute Myocardial Infarction, were interviewed during the index hospitalization (1992-93) and after 3-6 months. Resumption of sexual activity was defined as abstaining/decreasing or maintaining/increasing according to self-reported frequency post- vs. pre-MI. Patients were followed for all-cause and cause-specific mortality through national registries. A propensity score for sexual activity resumption was calculated, based on which inverse probability weighted Cox models were constructed to examine associations. Patients who maintained/increased frequency [n = 263 (53%)] were more likely to be of higher socioeconomic status and to express lower levels of depression than their abstained/decreased counterparts. In the propensity score-weighted synthetic sample, the distribution of measured baseline covariates was similar across exposure categories. During a median follow-up of 22 years, 211 (43%) patients died. Maintaining/increasing sexual activity frequency was inversely associated with all-cause mortality [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.48-0.88], compared with abstaining/reducing. The inverse association was more robust for non-cardiovascular mortality (HR 0.56, 95% CI 0.36-0.85) than cardiovascular mortality (HR 0.90, 95% CI 0.53-1.51). CONCLUSIONS: Resumption of sexual activity frequency within the first months after MI was strongly associated with improved long-term survival, highlighting the need for sexual counselling shortly after MI.

Reaching 80 Years of Age: Clinical, Behavioral, and Psychosocial Related Risk Factors in a Large Cohort of Israeli Working Men.

The objective of this study was to estimate the probability of long-term overall survival based on total number of risk factors (RF). We also sought to examine the role of midlife clinical, behavioral, and psychosocial predictors of longevity in a large cohort of Israeli men. This study was based on the Israeli Ischemic Heart Disease (IIHD) cohort that included over 10,000 men who were followed up for mortality over more than four decades. During the 43 years of follow-up, 4634 (46.1%) men survived to 80 years of age or older. We considered cigarette smoking, diabetes mellitus, high systolic blood pressure, hypercholesterolemia, low socioeconomic status, and serious family problems as RF at ages 40-65. Cox proportional hazards regression models, with age as the time scale, were constructed to estimate the hazard ratios (HRs) for failure to survive 80 years of age. Compared with men free of all the above RF, those with one identified RF (HR = 1.58, 95% CI: 1.42-1.75) and counterparts with two identified RF (HR = 2.18, 95% CI: 1.96-2.43) were at a significantly greater risk of death before 80. Additional RF further increased the risk of early mortality (HR = 3.62, 95% CI: 1.50-8.73 for men with 5 RF). The results suggest a role of physiological, behavioral, and psychological risk factors at midlife in predicting longevity.

Excess Body Weight and Long-Term Incidence of Lung and Colon Cancer in Men; Follow-Up Study of 43 Years.

Most evidence for an association between excess body weight and cancer risk has been derived from studies of relatively short duration with little reference to the effect on tumor site. This study was designed to evaluate the association between categories of body mass index (BMI: <20, 20-25, 25-30, and >30 kg/m2) and the incidence of colon and lung cancer over 43 years of follow-up (1963-2006), in 10,043 men from the Israeli Ischemic Heart Disease (IIHD) prospective cohort (mean age at baseline 49.3 years, mean BMI 25.7 kg/m2). Data from the Israel National Cancer Registry was linked with the IIHD, and the Cox proportional hazards regression model was applied to analyze the relative risks for lung and colon cancer across BMI categories at baseline. Three hundred cases of lung cancer (2.9%) and 328 cases of colon cancer (3.3%) were diagnosed in the total population. Applying a multivariate model adjusted for age, smoking intensity, and total cholesterol, higher BMI category was associated with an increased risk of colon cancer [HR = 1.22 (95% CI 1.02-1.45)], and with a decreased risk for lung cancer [HR = 0.66 (95% CI 0.56-0.77)]. In this long-term follow-up study over four decades, we observed a consistent dose-response pattern between BMI and increased risk for colon cancer, but decreased risk for lung cancer. Specific associations between excess body weight and cancer risk may suggest different patterns of body fat and cancer incidence at a given site.

Dissatisfaction with Married Life in Men Is Related to Increased Stroke and All-Cause Mortality.

The objectives of this study were to assess the association between marital satisfaction and specific and all-cause mortality, and to examine whether this association is independent of other known risk factors for early mortality. In this prospective cohort, male Israeli civil servants and municipal employees (n = 8945) underwent an extensive appraisal of health and behavioral patterns and were followed for more than three decades. Cox proportional hazards analysis was used to estimate the relative risks for stroke and all-cause mortality over time across marital satisfaction categories. During the 32 years of follow-up, 5736 (64.1%) died. Dissatisfaction with married life was related to increased long-term risk of stroke (HR = 1.94; 95%CI, 1.41-2.90) and all-cause mortality (HR = 1.21; 95%CI, 1.04-1.41). The latter association was of a similar order of magnitude to other known risk factors for early mortality, such as people with a history of smoking (HR = 1.37; 95%CI, 1.30-1.48) compared to people who have never smoked and for physically inactive participants (HR = 1.21; 95%CI, 1.14-1.37) compared to physically active participants. The results of our study suggest that marital dissatisfaction may predict an elevated risk of all-cause mortality. Assessing marital satisfaction and measuring the health benefits of marital education programs for couples should be implemented as part of health promotion strategies for the general population.

Holocaust exposure and late-life cognitive performance in men with coronary heart disease.

BACKGROUND: Holocaust victims experienced extreme physical and mental stress that could lead to prolonged deficits in psychological and physiological well-being. We aimed to examine whether exposure to Holocaust conditions is associated with cognitive function and decline in a sample of old male adults with coronary heart disease (CHD). METHODS: The sample included 346 individuals with CHD who participated in a clinical trial in 1990-1997 (mean age 56.7 ± 6.5 y). During 2004-2008 (mean age 71.8 ± 6.5 y) and 2011-2013 (mean age 77.1 ± 6.4 y) participants underwent computerized cognitive assessments. Exposure to Holocaust conditions was based on self-report at the second assessment. Linear regression and mixed-effect models were conducted to evaluate the associations between Holocaust survivorship and subsequent cognitive performance and rate of cognitive decline. RESULTS: Forty-Three participants (12%) survived concentration camps/ghettos, 69 (20%) were Holocaust survivors who escaped concentration camps/ghettos, and 234 (68%) were not Holocaust survivors. After adjustment for potential confounders, concentration camp/ghetto survivors had poorer global cognitive performance and poorer attention (ß = -3.90; 95%CI: 7.11;-0.68 and ß = -4.11; 95%CI: 7.83;-0.38, respectively) compared to individuals who were not exposed to Holocaust conditions. Additionally, participants who reported being at concentration camps/ghettoes had increased cognitive decline in global performance and executive function (ß = -0.19; 95%CI: 0.37;-0.008 and ß = -0.29; 95%CI: 0.53;-0.06, respectively) compared to participants who were not Holocaust survivors. Lastly, those who were Holocaust survivors but not in concentration camps/ghettos had greater decline in attention (ß = -0.11; 95%CI: 0.21;-0.01). DISCUSSION: Exposure to Holocaust conditions in early-life may be linked with poorer cognitive function and greater cognitive decline decades later in old-adults with CHD.

Overweight, Obesity, and Late-Life Sarcopenia Among Men With Cardiovascular Disease, Israel.

INTRODUCTION: Little is known about the association between obesity and sarcopenia - age-related loss of muscle mass and function - among patients with cardiovascular disease. We investigated the association between overweight, obesity, and sarcopenia among community-dwelling men in Israel with cardiovascular disease. METHODS: A subset of 337 men (mean age at baseline 56.7 [SD, 6.5]) who previously (1990-1997) participated in the Bezafibrate Infarction Prevention trial underwent a neurovascular evaluation as part of the Bezafibrate Infarction Prevention Neurocognitive Study 15.0 (SD, 3.0) years after baseline and a sarcopenia evaluation 19.9 (SD, 1.0) years after baseline. We applied a multinomial logistic model to estimate odds ratios and 95% CIs for 3 categories of sarcopenia: no evidence of sarcopenia (ie, robust), probable sarcopenia, and sarcopenia. RESULTS: We found sarcopenia among 54.3% of participants with obesity (body mass index [BMI, in kg/m2] ≥30.0), 37.0% of participants who were overweight (25.0 ≤ BMI ≤29.9), and 24.8% of participants with normal weight (BMI 18.5 to 24.9). In a comparison of BMI ≥25.0 and BMI <25.0, adjusting for covariates, the odds ratio of having probable sarcopenia was 3.27 (95% CI, 1.68-6.36) and having sarcopenia was 5.31 (95% CI, 2.50-11.27). CONCLUSION: We found a positive association between obesity and late-life sarcopenia and suggest that obesity might be an important modifiable risk factor related to sarcopenia among men with cardiovascular disease.

Role of psychosocial factors in long-term adherence to secondary prevention measures after myocardial infarction: a longitudinal analysis.

PURPOSE: Psychosocial factors have been linked to myocardial infarction (MI) outcomes. Whether psychosocial factors affect post-MI long-term adherence to secondary prevention recommendations remains uncertain. METHODS: Patients ≤65 years (n = 616) were assessed for optimism, perceived social support (PSS), sense of coherence (SOC), anxiety, and depression at initial hospitalization for acute MI (1992-1993). Adherence to secondary prevention measures was recorded in interviews 3-6 months, 1-2, 5, and 10-13 years after MI. Prevention score (proportion of recommendations met) was developed based on: (1) medication adherence; (2) exercise; (3) nonsmoking; (4) healthy diet; (5) maintaining recommended body weight. Associations between psychosocial factors and prevention scores were estimated using Generalized Estimating Equation models. The role of the prevention score in long-term survival was assessed using time-dependent Cox regression analysis. RESULTS: Average follow-up prevention scores ranged from 0.70 to 0.80 (SD, ≈0.20). After multivariable adjustment, PSS (ß = 0.087, P = .002, per 1 SD increase) and SOC (ß = 0.082, P = .006, per 1 SD increase) were positively associated with secondary prevention adherence. The prevention score predicted survival over 23-year follow-up (adjusted hazard ratio = 0.79; 95% CI: 0.68-0.91, per 1 SD increase). CONCLUSIONS: Psychosocial factors following MI, particularly PSS and SOC, were associated with long-term adherence to secondary prevention measures.

Blood pressure variability at midlife is associated with all-cause, coronary heart disease and stroke long term mortality.

OBJECTIVE: Elevated blood pressure (BP) is associated with cardiovascular mortality. BP variability (BPV) is also associated with cardiovascular mortality. However, most studies evaluated hypertensive patients with a relatively short follow-up. We investigated in male workers the association between BPV and long-term all-cause and specific-cause mortality. METHODS: Among 10 059 men, aged 40-65, tenured civil servants and municipal employees in Israel, 9398 participants who were examined in 1963, 1965 and 1968 had assessment of diabetic and coronary morbidity status and SBP levels. Participants underwent clinical and biochemical evaluations and BP measured in the recumbent position on the right arm. We conducted analysis for SD-SBP across study visits. Hazard ratios were calculated for 18 years all-cause mortality, coronary heart disease (CHD) and stroke mortality associated with quintile of SD-SBP, with the lowest quintile serving as a reference. RESULTS: Multivariate analysis yielded a significant association between SD-SBP and all-cause, CHD and stroke mortality. Age and SBP-adjusted hazard ratios of all-cause mortality was 1.02 [95% confidence interval (CI), 0.90-1.17], 1.06 (95% CI, 0.94-1.20), 1.20 (95% CI, 1.06-1.35) and 1.36 (95% CI, 1.21-1.53) (for quintile 2-5, respectively). The results of CHD and stroke mortality similarly and strongly indicated increasing age-adjusted mortality risk with increasing SD-SBP. Further adjustment for smoking, BMI, diabetes mellitus and coronary heart disease yielded similar results. CONCLUSION: In this cohort of tenured male workers, BPV taken over 5 years was clearly associated with 18-year all-cause, CHD and stroke mortality.

C-reactive protein in midlife is associated with depressive symptoms two decades later among men with coronary heart disease.

Aim: We investigated the relationship between midlife C-reactive protein (CRP) levels in men with coronary heart disease (CHD) and depressive symptoms at old age. CRP levels were measured in a subset of patients with CHD, who previously participated in a secondary prevention trial.Methods: Depressive symptoms were evaluated in survivors of the original cohort 15.0 ± 3 and 19.9 ± 1 years later (T1, n = 463 and T2, n = 314 respectively) using the Geriatric Depression Scale (GDS), 15-item version. Logistic regression was used to estimate ORs and 95%CIs for presence of potentially clinically significant depressive symptoms (GDS ≥5) at T1 and T2.Results: Adjusting for demographic and health-related variables, the OR (95%CI) for GDS ≥5 was 1.23 (0.65-2.33); p = .53 at T1 and 2.36 (1.16-4.83); p = .018 at T2 in the top CRP tertile compared to the others. Similarly, consistently high CRP levels in the top tertile at baseline and 2 years later, were associated with OR of 2.85 (95%CI 1.29-6.30); p = .01 for GDS ≥5 at T2.Conclusions: Presence and persistence of low-grade inflammation in men with CHD during midlife are associated with increased risk of depressive symptoms twenty years later. Among middle aged men with CHD, low-grade inflammation may provide an important added value for prediction of depression in old age.

Frequency of Sexual Activity and Long-term Survival after Acute Myocardial Infarction.

BACKGROUND: Previous studies have shown an inverse relationship between sexual activity and mortality in the general population. We evaluated the association between sexual activity and long-term survival among patients with acute myocardial infarction. METHODS: Patients aged ≤65 years (n=1120; mean age, 53) discharged from 8 hospitals in central Israel after first myocardial infarction from 1992-1993 were followed for mortality through 2015. Frequency of sexual activity was self-reported during the index hospitalization (baseline; referring to the year preceding the infarct) and after 5 and 10-13 years, along with sociodemographic and clinical data. Cox proportional hazards models were constructed to estimate the association with all-cause mortality in time-dependent sexual activity categories. RESULTS: At baseline, a > once per week frequency of sexual activity was reported by 42% of the patients, whereas no sexual activity was reported by 6%. After 10-13 years, the rates were 21% and 27%, respectively. Lower sexual activity was associated with older age, female sex, lack of a steady partner and more comorbidities. During follow-up, 524 deaths (47%) occurred. An inverse relationship was observed between sexual activity frequency and death, with hazard ratios (95% confidence intervals) of 0.30 (0.23-0.38) for > once per week, 0.36 (0.28-0.46) for once per week, and 0.53 (0.42-0.66) for < once per week, compared with none. After adjusting for relevant confounding factors, the estimates were attenuated to 0.68 (0.50-0.91), 0.63 (0.48-0.83), and 0.72 (0.57-0.93), respectively (P for trend = .004). CONCLUSIONS: Using repeated assessments of sexual activity after myocardial infarction, an inverse association was demonstrated with mortality, which was only partly accounted for by measured potential confounders.

Midlife resting heart rate, but not its visit-to-visit variability, is associated with late-life frailty status in men with coronary heart disease.

BACKGROUND: Autonomic imbalance is linked with multiple health conditions, yet its associations with frailty were rarely studied. We assessed the relationship of resting heart rate (RHR) and visit-to-visit heart rate variability (HRV) with future frailty among elderly men with coronary heart disease (CHD). METHODS: Three-hundred-six community-dwelling men with CHD who participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1998; mean age 56.6 ± 6.5 years) underwent assessment of physical frailty in 2011-2013 (mean age 77.0 ± 6.4 years). Mean RHR and visit-to-visit HRV were calculated from electrocardiogram as indicators of autonomic imbalance. Nominal logistic and linear regression models were used to assess the relationships of RHR and HRV with frailty status and its components (i.e. gait speed, grip strength, weight loss, exhaustion and activity), respectively. Adjustments were made for various demographic, clinical and metabolic covariates. RESULTS: Of the 306 men, 81 (26%) were frail and 117 (38%) were prefrail. After controlling for potential confounders, RHR, but not visit-to-visit HRV, was associated with higher odds of being prefrail [OR = 1.44 (95%CI 1.15, 1.79)] and frail [OR = 1.35 (95%CI 1.03, 1.77)]. Each 5-bpm increase in RHR was associated with weaker grip (ß= -1.12 ± 0.32 kg; p-value < .001) and slower gait speed (ß = 0.19 ± 0.08s/m; p-value = .022). CONCLUSIONS: Midlife RHR may be associated with late-life frailty in men with CHD.

Angina pectoris severity and late-life frailty among men with cardiovascular disease.

OBJECTIVE: We investigated the association between severity of angina pectoris (AP) and subsequent late-life frailty among men with cardiovascular disease (CVD). METHOD: A subset of 351 men (mean age at baseline 56.7 ± 6.5 years) who previously participated in the Bezafibrate Infarction Prevention, BIP trial (1990-1997) underwent a neurovascular evaluation as part of the BIP Neurocognitive study 15.0 ± 3.0 years after baseline (T1) and a frailty evaluation according to Fried 19.9 ± 1.0 years after baseline (T2). Severity of AP was assessed at baseline of the BIP trial using the Canadian Cardiovascular Society angina classification. We assessed the odds of being in the advanced rank of frailty status (robust, pre-frail, and frail) using ordered logistic regression. RESULTS: Among 351 participants, 134 (38.2%) were classified as pre-frail and 100 (28.5%) as frail. Frailty was found among 42% participants in the AP class ≥2 and among 26% participants in the AP class <2. Adjusting for demographic, health-related and cognitive variables, odds ratio (OR), and 95% confidence interval (95% CI) for advanced rank of frailty was 2.68 (95% CI: 1.29-5.59) comparing AP class ≥2 to AP class <2. DISCUSSION: Among men with CVD, severity of AP should be taken into risk consideration due to its strong association with late-life frailty, particularly among inactive participants and participants with cerebral microvascular damage.