Lifestyle factors,cardiovascular disease and all-cause mortality in middle-aged and elderly women: a systematic review and meta-analysis

Cardiovascular disease (CVD) risk factors, incidence and death increases from around the time of menopause comparing to women in reproductive age. A healthy lifestyle can prevent CVD, but it is unclear which lifestyle factors may help maintain and improve cardiovascular health for women after menopausal transition. We conducted a systematic review and meta-analysis of prospective cohort studies to evaluate the association between modifiable lifestyle factors (specifically smoking, physical activity, alcohol intake, and obesity), with CVD and mortality in middle-aged and elderly women. Pubmed, Embase, among other databases and reference lists were searched until February 29th, 2016. Study specific relative risks (RR) were meta-analyzed using random effect models. We included 59 studies involving 5,358,902 women. Comparing current versus never smokers, pooled RR were 3.12 (95% CI 2.15–4.52) for CHD incidence, 2.09 (95% CI 1.51–2.89) for stroke incidence, 2.76 (95% CI 1.62–4.71) for CVD mortality and 2.22 (95% CI 1.92–2.57) for all-cause mortality. Physical activity was associated with a decreased risk of 0.74 (95% CI 0.67–0.80) for overall CVD, 0.71 (95% CI 0.67–0.75) for CHD, 0.77 (95% CI 0.70–0.85) for stroke, 0.70 (95% CI 0.58–0.84) for CVD mortality and 0.71 (95% CI 0.65–0.78) for all-cause mortality. Comparing moderate drinkers versus non-drinkers, the RR was 0.72 (95% CI 0.56–0.91) for CHD, 0.63 (95% CI 0.57–0.71) for CVD mortality and 0.80 (95% CI 0.76–0.84) for all-cause mortality. For women with BMI 30–35 kg/m² the risk was 1.67 (95% CI 1.24–2.25) for CHD and 2.3 (95% CI 1.56–3.40) for CVD mortality, compared to normal weight. Each 5 kg/m² increase in BMI was associated with 24% (95% CI 16–33%) higher risk for all-cause mortality. This meta-analysis suggests that physical activity and moderate alcohol intake were associated with a reduced risk for CVD and mortality. Smoking and higher BMI were associated with an increased risk of these endpoints. Adherence to a healthy lifestyle may substantially lower the burden of CVD and reduce the risk of mortality among middle-aged and elderly women. However, this review highlights important gaps, as lack of standardized methods in assessing lifestyle factors and lack of accurate information on menopause status, which should be addressed by future studies in order to understand the role of menopause on the association between lifestyle factors and cardiovascular events.     

Anthropometric measures and risk of all-cause and cardiovascular mortality: An 18 years follow-up

BackgroundThe contribution of anthropometric measures to predict mortality in normal-weight subjects is unclear. We aimed to study the association of central obesity measures, e.g., waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), with the risk of all-cause and CVD mortality.MethodsIn a prospective population-based Tehran Lipid and Glucose Study, 8287 participants aged ≥30 y, followed for a median of 18 years. The association of WC, WHR and WHtR with the risk for mortality was estimated using multivariate Cox proportional hazard models in different BMI groups.ResultsWe documented 821 deaths, of which 251 were related to CVD mortality. Normal weight individuals with central obesity were significantly at increased risk of all-cause (HR: 1.5; 95% CI: 1.10, 2.1) and CVD mortality (HR: 1.6; 95% CI: 0.92, 2.9) compared with normal-weight individuals without central obesity; the risk remained significant only in women. Also, normal-weight women (not men) with high WHR were at increased risk of all-cause (HR: 1.7; 95% CI: 1.0, 2.8) and CVD mortality (HR: 5.9; 95% CI: 1.5, 23.2). High WHtR increased the risk of all-cause (HR: 1.5; 95% CI: 1.2, 1.8) and CVD mortality (HR: 1.8; 95% CI: 1.2, 2.7) which remained significant in normal-weight men and women. All central obesity indicators were significantly associated with all-cause and CVD mortality in subjects aged under 65.ConclusionEven in normal-weight individuals, WC and WHR in women and WHtR in both sexes are predictors of all-cause and CVD mortality. WHtR shows a stronger association, especially in the population aged under 65.     

Dietary Sodium and Potassium Intake and Risk of Non-Fatal Cardiovascular Diseases: The Million Veteran Program

Objective: To examine the association between intakes of sodium and potassium and the ratio of sodium to potassium and incident myocardial infarction and stroke. Design, Setting and Participants: Prospective cohort study of 180,156 Veterans aged 19 to 107 years with plausible dietary intake measured by food frequency questionnaire (FFQ) who were free of cardiovascular disease (CVD) and cancer at baseline in the VA Million Veteran Program (MVP). Main outcome measures: CVD defined as non-fatal myocardial infarction (MI) or acute ischemic stroke (AIS) ascertained using high-throughput phenotyping algorithms applied to electronic health records. Results: During up to 8 years of follow-up, we documented 4090 CVD cases (2499 MI and 1712 AIS). After adjustment for confounding factors, a higher sodium intake was associated with a higher risk of CVD, whereas potassium intake was inversely associated with the risk of CVD [hazard ratio (HR) comparing extreme quintiles, 95% confidence interval (CI): 1.09 (95% CI: 0.99–1.21, p trend = 0.01) for sodium and 0.87 (95% CI: 0.79–0.96, p trend = 0.005) for potassium]. In addition, the ratio of sodium to potassium (Na/K ratio) was positively associated with the risk of CVD (HR comparing extreme quintiles = 1.26, 95% CI: 1.14–1.39, p trend < 0.0001). The associations of Na/K ratio were consistent for two subtypes of CVD; one standard deviation increment in the ratio was associated with HRs (95% CI) of 1.12 (1.06–1.19) for MI and 1.11 (1.03–1.19) for AIS. In secondary analyses, the observed associations were consistent across race and status for diabetes, hypertension, and high cholesterol at baseline. Associations appeared to be more pronounced among participants with poor dietary quality. Conclusions: A high sodium intake and a low potassium intake were associated with a higher risk of CVD in this large population of US veterans.     

Dietary total antioxidant capacity is inversely associated with all-cause and cardiovascular disease death of US adults

Purpose

Although evidence strongly supports that antioxidant-rich diets reduce risk of chronic disease and mortality, findings from the previous studies on the effect of individual antioxidants on mortality have been inconsistent. The aim of this study was to assess the relationship between dietary total antioxidant capacity (TAC) and all-cause and disease-specific mortality in a representative sample of the US population.

Methods

A total of 23,595 US adults aged 30 years and older in NHANES 1988–1994 and 1999–2004 were selected for this study. Dietary TAC was calculated from 1-day 24-h diet recall data at baseline and all-cause, cancer and cardiovascular disease (CVD) mortality was assessed through December 31, 2011.

Results

During a mean follow-up of 13 years, deaths from all-cause, cancer and CVD were 7157, 1578, and 2155, respectively. Using cause-specific Cox proportional hazards models, inverse associations and linear trends were observed between dietary TAC and all-cause mortality [highest quartile (Q4) versus Q1 ref. HR 0.78; 95% CI 0.71–0.86], cancer mortality (Q4 versus Q1 ref. HR 0.75; 95% CI 0.60–0.93), and CVD mortality (Q4 versus Q1 ref. HR 0.83; 95% CI 0.69–0.99), respectively, after adjusting for age, sex, ethnicity, and total energy intake. The inverse association and linear trend still remained between dietary TAC and all-cause mortality (Q4 versus Q1 ref. HR 0.79; 95% CI 0.71–0.87) and CVD mortality (Q4 versus Q1 ref. HR 0.74; 95% CI 0.61–0.89) when further adjusted for relevant covariates.

Conclusions

These findings support that antioxidant-rich diets are beneficial to reducing risk of death from all-cause and CVD.

     

Prospective Analysis of Health and Mortality Risk in Veteran and Non-Veteran Participants in the Women's Health Initiative

BackgroundThe health of postmenopausal women veterans is a neglected area of study. A stronger empirical evidence base is needed, and would inform the provision of health care for the nearly 1 million U.S. women veterans currently 50 years of age or older. To this end, the present work compares salient health outcomes and risk of all-cause mortality among veteran and non-veteran participants of the Women's Health Initiative (WHI).MethodsThis study features prospective analysis of long-term health outcomes and mortality risk (average follow-up, 8 years) among the 3,706 women veterans and 141,009 non-veterans who participated in the WHI Observational Study or Clinical Trials. Outcome measurements included confirmed incident cases of cardiovascular disease (CVD), cancer, diabetes, hip fractures, and all-cause mortality.ResultsWe identified 17,968 cases of CVD, 19,152 cases of cancer, 18,718 cases of diabetes, 2,817 cases of hip fracture, and 13,747 deaths. In Cox regression models adjusted for age, sociodemographic variables, and health risk factors, veteran status was associated with significantly increased risk of all-cause mortality (hazard ratio [HR], 1.13; 95% CI, 1.03–1.23), but not with risk of CVD (HR, 1.00; 95% CI, 0.90–1.11), cancer (HR, 1.04; 95% CI, 0.95–1.14), hip fracture (HR, 1.16; 95% CI, 0.94–1.43), or diabetes (HR, 1.00; 95% CI, 0.89–1.1).ConclusionsWomen veterans' postmenopausal health, particularly risk for all-cause mortality, warrants further consideration. In particular, efforts to identify and address modifiable risk factors associated with all-cause mortality are needed.     

Coffee Consumption and the Risk of All-Cause and Cause-Specific Mortality in the Korean Population

BackgroundThere is a dearth of information regarding the association between coffee consumption and its health effects with respect to mortality among Korean people.ObjectiveThe aim of this study was to examine the association between coffee consumption and all-cause mortality and cause-specific mortality risks in the Korean population.DesignThis prospective cohort study had a median follow-up period of 9.1 years.Participants/settingIn total, 173,209 participants aged 40 years and older from the Health Examinees study were enrolled between 2004 and 2013. The analytic sample included 110,920 participants without diabetes, cardiovascular disease (CVD), or cancer at baseline who could be linked with their death information.Main outcome measuresDeaths of participants until December 31, 2018 were ascertained using the death certificate database of the National Statistical Office. Cause of death was classified according to the International Classification of Diseases, 10th Revision.Statistical analyses performedParticipants were categorized according to the amount and type of coffee consumed. Cox proportional hazards regression analysis was performed to estimate the hazard ratio (HR) and 95%CI of all-cause mortality and cause-specific mortality, such as CVD and cancer mortality.ResultsCompared with nonconsumers of coffee, participants who consumed > 3 cups/day had a reduced risk of all-cause mortality (HR 0.79, 95% CI 0.66 to 0.95). Participants who consumed ≤1 cup/day and 1 to 3 cups/day had a reduced risk of CVD mortality (≤1 cup/day: HR 0.58, 95% CI 0.69 to 0.94; 1 to 3 cups/day: HR 0.62, 95% CI 0.41 to 0.96).ConclusionsThis study provides evidence that greater coffee consumption is associated with a decreased risk of all-cause mortality and moderate coffee consumption (approximately 3 cups/day) is associated with a decreased risk of CVD mortality, regardless of the type of coffee, in a Korean population.     

Oat Intake and Risk of Type 2 Diabetes,Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis

Cardiovascular disease (CVD) and type 2 diabetes (T2D) remain the top disease and mortality burdens worldwide. Oats have been shown to benefit cardiovascular health and improve insulin resistance. However, the evidence linking oat consumption with CVD, T2D and all-cause mortality remains inconclusive. We conducted a comprehensive systematic review and meta-analysis of prospective cohort studies to evaluate the associations between oat consumption and risks of T2D, CVD and all-cause mortality in the general population. Five electronic databases were searched until September, 2020. Study specific relative risks (RR) were meta-analyzed using random effect models. Of 4686 relevant references, we included 9 articles, based on 8 unique studies and 471,157 participants. Comparing oat consumers versus non-consumers, RRs were 0.86 (95% CI 0.72–1.03) for T2D incidence and 0.73 (95% CI 0.5–1.07) for combined CVD incidence. Comparing participants with highest versus lowest oat intake, RRs were 0.78 (95% CI 0.74–0.82) for T2D incidence, 0.81 (95% CI 0.61–1.08) for CHD incidence and 0.79 (95% CI 0.59–1.07) for stroke. For all-cause mortality one study based on three cohorts found RR for men and women were 0.76 (95% CI 0.69–0.85) and 0.78 (95% CI 0.70–0.87), respectively. Most studies (n = 6) were of fair to good quality. This meta-analysis suggests that consumption of oat could reduce the risk for T2D and all-cause mortality, while no significant association was found for CVD. Future studies should address a lack of standardized methods in assessing overall oat intake and type of oat products, and investigate a dose-dependent response of oat products on cardiometabolic outcomes in order to introduce oat as preventive and treatment options for the public.     

Predicting cause-specific mortality of older men living in the veterans home by handgrip strength and walking speed: a 3-year, prospective cohort study in Taiwan

ObjectiveTo determine prognostic value of handgrip strength (HGS) and walking speed (WS) in predicting the cause-specific mortality for older men.DesignProspective cohort study.SettingBanciao Veterans Care Home.Participants558 residents aged 75 years and older.MeasurementsAnthropometric data, lifestyle factors, comorbid conditions, biomarkers, HGS, and WS at recruitment; all-cause and cause-specific mortality at 3 years after recruitment.ResultsDuring the study period, 99 participants died and the baseline HGS and WS were significantly lower than survivors (P both <.001). Cox survival analysis showed that subjects with slowest quartile of WS were at significantly higher risk of all-cause mortality and cardiovascular mortality (hazard ratio [HR] 3.55, 95% confidence interval [CI] 1.69–7.43; HR 11.55, 95% CI 2.30–58.04, respectively), whereas the lowest quartile of HGS significantly predicted a higher risk of infection-related death (HR 5.53, 95% CI 1.09–28.09). Participants in the high-risk status with slowest quartile for WS but not those in the high-risk status with weakest quartile for HGS had similar high risk of all-cause mortality with the group with combined high-risk status (HR 2.96, 95% CI 1.68–5.23; HR 2.58, 95% CI 1.45–4.60, respectively) compared with the participants without high-risk status (reference group).ConclusionsSlow WS predicted all-cause and cardiovascular mortality, whereas weak HGS predicted a higher risk of infection-related death among elderly, institutionalized men in Taiwan. Combining HGS with WS simultaneously had no better prognostic value than using WS only in predicting all-cause mortality.     

Leisure time physical activity and long-term cardiovascular and cancer outcomes: the Busselton Health Study

The study aimed to investigate whether meeting leisure time physical activity recommendations was associated with reduced incident and fatal cancer or cardiovascular disease (CVD) in a community-based cohort of middle- to late-aged adults with long-term follow-up. At baseline, 2,320 individuals were assessed on a large number of lifestyle and clinical parameters including their level of physical activity per week, other risk factors (e.g. smoking and alcohol use) various anthropometric measures, blood tests and medical history. Individuals were linked to hospital and mortality registry data to identify future cancer and cardiovascular events (fatal and non-fatal) out to 15 years of follow-up. Cox regression analyses adjusted for relevant confounders identified a priori were used to estimate risk for all-cause, cancer-specific and CVD-specific mortality. In the full cohort an estimated 21 % decreased risk for all-cause mortality (HR 0.79; 95 % CI 0.66–0.96) and 22 % decreased risk for fatal/non-fatal CVD events (HR 0.78; 95 % CI 0.66–0.92) was associated with baseline self-reported physical activity levels of 150 min or more. After exclusion of those with chronic co-morbidities (CVD, cancer, diabetes, chronic obstructive pulmonary disease, hypertension treatment) at baseline, lower risk for fatal/non-fatal CVD events remained significantly associated with 150 min or more of physical activity (HR 0.77; 95 % CI 0.62–0.96). Results from this well established prospective community-based cohort study support the role of leisure time physical activity in reducing all-cause mortality and CVD events (fatal/nonfatal) in the broader population studied. The data also suggest that physical activity associated reductions in risk for CVD events (fatal/nonfatal) were not overly impacted by prevalent key non-communicable diseases.     

Cardiovascular Health Metrics and All-cause and Cardiovascular Disease Mortality Among Middle-aged Men in Korea: The Seoul Male Cohort Study

Objectives

This study estimated the association of cardiovascular health behaviors with the risk of all-cause and cardiovascular disease (CVD) mortality in middle-aged men in Korea.

Methods

In total, 12 538 men aged 40 to 59 years were enrolled in 1993 and followed up through 2011. Cardiovascular health metrics defined the following lifestyle behaviors proposed by the American Heart Association: smoking, physical activity, body mass index, diet habit score, total cholesterol, blood pressure, and fasting blood glucose. The cardiovascular health metrics score was calculated as a single categorical variable, by assigning 1 point to each ideal healthy behavior. A Cox proportional hazards regression model was used to estimate the hazard ratio of cardiovascular health behavior. Population attributable risks (PARs) were calculated from the significant cardiovascular health metrics.

Results

There were 1054 total and 171 CVD deaths over 230 690 person-years of follow-up. The prevalence of meeting all 7 cardiovascular health metrics was 0.67%. Current smoking, elevated blood pressure, and high fasting blood glucose were significantly associated with all-cause and CVD mortality. The adjusted PARs for the 3 significant metrics combined were 35.2% (95% confidence interval [CI], 21.7 to 47.4) and 52.8% (95% CI, 22.0 to 74.0) for all-cause and CVD mortality, respectively. The adjusted hazard ratios of the groups with a 6-7 vs. 0-2 cardiovascular health metrics score were 0.42 (95% CI, 0.31 to 0.59) for all-cause mortality and 0.10 (95% CI, 0.03 to 0.29) for CVD mortality.

Conclusions

Among cardiovascular health behaviors, not smoking, normal blood pressure, and recommended fasting blood glucose levels were associated with reduced risks of all-cause and CVD mortality. Meeting a greater number of cardiovascular health metrics was associated with a lower risk of all-cause and CVD mortality.     

Interaction of Body Mass Index and Diabetes as Modifiers of Cardiovascular Mortality in a Cohort Study

Objectives

Diabetes and obesity each increases mortality, but recent papers have shown that lean Asian persons were at greater risk for mortality than were obese persons. The objective of this study is to determine whether an interaction exists between body mass index (BMI) and diabetes, which can modify the risk of death by cardiovascular disease (CVD).

Methods

Subjects who were over 20 years of age, and who had information regarding BMI, past history of diabetes, and fasting blood glucose levels (n=16 048), were selected from the Korea Multi-center Cancer Cohort study participants. By 2008, a total of 1290 participants had died; 251 and 155 had died of CVD and stroke, respectively. The hazard for deaths was calculated with hazard ratio (HR) and 95% confidence interval (95% CI) by Cox proportional hazard model.

Results

Compared with the normal population, patients with diabetes were at higher risk for CVD and stroke deaths (HR, 1.84; 95% CI, 1.33 to 2.56; HR, 1.82; 95% CI, 1.20 to 2.76; respectively). Relative to subjects with no diabetes and normal BMI (21 to 22.9 kg/m²), lean subjects with diabetes (BMI <21 kg/m²) had a greater risk for CVD and stroke deaths (HR, 2.83; 95% CI, 1.57 to 5.09; HR, 3.27; 95% CI, 1.58 to 6.76; respectively), while obese subjects with diabetes (BMI ≥25 kg/m²) had no increased death risk (p-interaction <0.05). This pattern was consistent in sub-populations with no incidence of hypertension.

Conclusions

This study suggests that diabetes in lean people is more critical to CVD deaths than it is in obese people.     

Health-related behaviours as predictors of mortality and morbidity in Australian Aborigines

OBJECTIVE: To examine predictors of coronary heart disease (CHD) and all-cause mortality in Aboriginal Australians. METHOD: In 1988-89, a survey of Western Australian Aborigines (256 women, 258 men) aged 15-88 years documented diet, alcohol and smoking habits. Linkage to mortality and hospital admissions to the end of 2002 provided longitudinal data for modelling of coronary heart disease endpoints and all-cause mortality using Cox regression. RESULTS: Coronary heart disease risk increased with smoking (HR 2.62, 95% CI: 1.19, 5.75), consumption of processed meats >once/week (HR 2.21, 95% CI: 1.05, 4.63), eggs >twice/week (HR 2.59, 95% CI: 1.11, 6.04) and using spreads on bread (HR 3.14. 95% CI: 1.03, 9.61). All-cause mortality risk was lower with exercise >once/week (HR 0.51, 95% CI 0.26, 1.05), increased in ex-drinkers (HR 3.66, 95% CI: 1.08, 12.47), heavy drinkers (HR 5.26, 95% CI: 1.46, 7.52) and with consumption of take away foods >nine times/month (HR 1.78, 95% CI 0.96, 3.29). Greater alcohol intake, smoking and adverse dietary choices clustered in 53% of men and 56% of women and increased risk of coronary heart disease (HR 2.1, 95% CI: 1.1, 4.0) and all-cause mortality (HR 2.3, 95% CI: 1.2, 4.2). CONCLUSION: Lifestyle in Aboriginal Australians predicts coronary heart disease and all-cause mortality. Clustering of adverse behaviours is common and increases risk of coronary heart disease and death.     

Frailty Status Predicts All-Cause and Cause-Specific Mortality in Community Dwelling Older Adults

ObjectivesTo examine the relationship between frailty status and risk of all-cause and cause-specific mortality.DesignLongitudinal cohort study with an 11-year follow up.Setting and participantsData from the Survey on Health, Aging and Retirement in Europe (SHARE) were used. In the analysis, we included data from 11 European countries. We included men and women older than 50 years residing in Europe. Overall, 24,634 participants were analyzed with a mean age of 64.2 (9.8), 53.6% female, where 14.7% and 6.9% were found to be prefrail or frail, respectively, at the baseline.MethodsFrailty status was calculated using the SHARE–Frailty Instrument, categorizing the participants as robust, prefrail, and frail. Multivariate Cox regression models were used to estimate the risk of all-cause and cause-specific (stroke, heart attack, other cardiovascular disease, cancer, respiratory illness, infectious, and digestive and other) mortality.ResultsDuring the follow-up, and after adjusting for sex, age, education, body mass index, smoking, alcohol consumption, and number of comorbidities, frailty was associated with a higher risk of all-cause (HR 2.17, 95% CI 1.90-2.48) and mortality due to stroke (HR 2.06, 95% CI 1.37-3.10), heart attack (HR 1.67, 95% CI 1.19-2.34), other cardiovascular disease (HR 2.77, 95% CI 1.87-4.12), cancer (HR 2.11, 95% CI 1.63-2.73), respiratory disease (HR 2.76, 95% CI 1.66-4.60), infectious diseases (HR 1.79, 95% CI 1.03-3.11), and digestive and other causes (HR 2.02, 95% CI 1.51-2.71). Prefrailty was associated with a higher risk of all-cause (HR 1.47, 95% CI 1.31-1.63), heart attack (HR 1.31, 95% CI 1.01-1.72), other cardiovascular disease (HR 2.03, 95% CI 1.46-2.81), respiratory disease (HR 1.70, 95% CI 1.09-2.65), and digestive and other causes (HR 1.50, 95% CI 1.18-1.91) mortality.Conclusions and implicationsBaseline prefrailty and frailty are associated with increased all-cause and cause-specific mortality over an 11-year follow up. Public health policy should include preventive programs aimed at older adults to prevent frailty and reduce mortality.     

Troponin T,B-type natriuretic peptide,C-reactive protein,and cause-specific mortality

PurposeWe sought to evaluate the associations of high-sensitivity troponin T (Hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high sensitivity C-reactive protein (Hs-CRP) with mortality from any cause, cardiovascular disease (CVD), coronary heart disease (CHD), stroke, cancer, and respiratory disease in the Atherosclerosis Risk in Communities cohort.MethodsWe included 11,193 participants aged 54 to 74 years, initially free of the conditions being studied, and who had biomarkers measured. Participants were followed for a mean of 9.9 years.ResultsHazard ratios (HR), adjusted for multiple risk factors, for mortality in participants in the highest Hs-TnT category compared with those with undetectable levels were: Total 3.42 (95% confidence interval [CI], 2.75–4.26); CVD, 7.34 (95% CI, 4.64–11.6); CHD, 6.06 (95% CI, 2.91–12.6); stroke, 3.31 (95% CI, 1.26–8.66); cancer, 1.60 (95% CI, 1.08–2.38); and respiratory, 3.85 (95% CI, 1.39–10.7). Comparing the highest NT-proBNP quintile with those in the lowest quintile, the adjusted HRs for mortality were: Total, 3.05 (95% CI, 2.46–3.77); CVD, 7.48 (95% CI, 4.67–12.0); CHD, 4.07 (95% CI, 2.07–7.98); and stroke, 10.4 (95% CI, 2.26–47.7). Comparing extreme Hs-CRP quintiles, the adjusted HRs for mortality were: Total, 1.61 (95% CI, 1.32–1.97); CVD, 1.76 (95% CI, 1.19–2.62); and respiratory, 3.36 (95% CI, 1.34–8.45). Having multiple markers elevated simultaneously greatly increased cause-specific mortality risks.ConclusionsGreater levels of Hs-TnT, NT-proBNP and Hs-CRP are associated with increased risk of death, not just from CVD, but also from some noncardiovascular causes.     

Association between Dietary Diversity and All-Cause Mortality: A Multivariable Model in a Mediterranean Population with 18 Years of Follow-Up

We evaluated the relationship between the dietary diversity score (DDS) and all-cause, CVD and cancer mortality in an adult Mediterranean population. We analyzed the data of 1540 participants from the Valencia Nutrition Survey. The DDS was estimated using a validated food frequency questionnaire and was categorized into quartiles (Q), where the first quartile indicates the lowest dietary diversity. Deaths were ascertained during an 18-year follow-up period. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). There were 403 deaths during the follow-up period (40% due to CVD). An inverse association was observed between the DDS and all-cause and CVD mortality. Compared with participants in the lowest DDS quartile (Q1), participants in the highest DDS quartile (Q4) showed 32% and 45% less risk of death for all-cause and CVD mortality, in sex- and age-adjusted models, respectively. Regarding the food groups in the DDS, an inverse association was identified between total vegetable consumption diversity and all-cause and CVD mortality in the highest quartiles, (Q3 vs. Q1, HR: 0.70; 95% CI: 0.50, 0.99) and (Q4 vs. Q1, HR: 0.52; 95% CI: 0.30, 0.91), respectively. This study suggests that a higher diversity in food intake, particularly in vegetables, may be associated with a lower risk of all-cause and CVD mortality. This association should be further investigated in other wider populations.     

Meal Skipping and Shorter Meal Intervals Are Associated with Increased Risk of All-Cause and Cardiovascular Disease Mortality among US Adults

BackgroundPrevious dietary studies and current dietary guidelines have mainly focused on dietary intake and food patterns. Little is known about the association between eating behaviors such as meal frequency, skipping and intervals, and mortality.ObjectiveThe objective was to examine the associations of meal frequency, skipping, and intervals with all-cause and cardiovascular disease (CVD) mortality.DesignThis was a prospective study.Participants/settingA total of 24,011 adults (aged ≥40 years) who participated in the National Health and Nutrition Examination Survey 1999-2014 were included in this study. Eating behaviors were assessed using 24-hour recall. Death and underlying causes of death were ascertained by linkage to death records through December 31, 2015.Main outcome measuresThe outcomes were all-cause and CVD mortality.Statistical analyses performedMultivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) of all-cause and CVD mortality.ResultsDuring 185,398 person-years of follow-up period, 4,175 deaths occurred, including 878 cardiovascular deaths. Most participants ate three meals per day. Compared with participants eating three meals per day, the multivariable-adjusted HRs for participants eating one meal per day were 1.30 (95% CI 1.03 to 1.64) for all-cause mortality, and 1.83 (95% CI 1.26 to 2.65) for CVD mortality. Participants who skipped breakfast have multivariable-adjusted HRs 1.40 (95% CI 1.09 to 1.78) for CVD mortality compared with those who did not. The multivariable-adjusted HRs for all-cause mortality were 1.12 (95% CI 1.01 to 1.24) for skipping lunch and 1.16 (95% CI 1.02 to 1.32) for skipping dinner compared with those who did not. Among participants eating three meals per day, the multivariable-adjusted HR for participants with an average interval of ≤4.5 hours in two adjacent meals was 1.17 (95% CI 1.04 to 1.32) for all-cause mortality, comparing with those having a meal interval of 4.6 to 5.5 hours.ConclusionsIn this large, prospective study of US adults aged 40 years or older, eating one meal per day was associated with an increased risk of all-cause and CVD mortality. Skipping breakfast was associated with increased risk of CVD mortality, whereas skipping lunch or dinner was associated with increased risk of all-cause mortality. Among participant with three meals per day, a meal interval of ≤4.5 hours in two adjacent meals was associated with higher all-cause mortality.     

Ultra-Processed Food Consumption and Adult Mortality Risk: A Systematic Review and Dose–Response Meta-Analysis of 207,291 Participants

We performed a systematic review and dose–response meta-analysis of observational studies assessing the association between UPF consumption and adult mortality risk. A systematic search was conducted using ISI Web of Science, PubMed/MEDLINE, and Scopus electronic databases from inception to August 2021. Data were extracted from seven cohort studies (totaling 207,291 adults from four countries). Using a random-effects model, hazard ratios (HR) of pooled outcomes were estimated. Our results showed that UPF consumption was related to an enhanced risk of all-cause mortality (HR = 1.21; 95% CI: 1.13, 1.30; I² = 21.9%; p < 0.001), cardiovascular diseases (CVDs)-cause mortality (HR = 1.50; 95% CI: 1.37, 1.63; I² = 0.0%; p < 0.001), and heart-cause mortality (HR = 1.66; 95% CI: 1.50, 1.85; I² = 0.0%; p = 0.022), but not cancer-cause mortality. Furthermore, our findings revealed that each 10% increase in UPF consumption in daily calorie intake was associated with a 15% higher risk of all-cause mortality (OR = 1.15; 95% CI: 1.09, 1.21; I² = 0.0%; p < 0.001). The dose–response analysis revealed a positive linear association between UPF consumption and all-cause mortality (P_nonlinearity = 0.879, P_{dose–response} = p < 0.001), CVDs-cause mortality (P_nonlinearity = 0.868, P_{dose–response} = p < 0.001), and heart-cause mortality (P_nonlinearity = 0.774, P_{dose–response} = p < 0.001). It seems that higher consumption of UPF is significantly associated with an enhanced risk of adult mortality. Despite this, further experimental studies are necessary to draw a more definite conclusion.     

Lifestyle and ethnicity play a role in all-cause mortality

The Israeli population is characterized by its marked ethnic diversity. These ethnic groups (originating mainly from Yemen/Aden, the Middle East, North Africa and Europe/America) have kept traditional distinct lifestyle habits and exhibit different morbidity and mortality trends. The aim of the present study was to evaluate the associations among ethnic background, lifestyle patterns and 18-y all-cause mortality. A subgroup of 632 individuals aged 41-70 y, drawn from a larger stratified cohort from the Israel Glucose Intolerance, Obesity and Hypertension study, were personally interviewed, using a quantified food-frequency questionnaire, including most food items consumed by the different subpopulations in Israel. Physical activity was also evaluated, as well as smoking status. Weight, height and blood pressure (BP) measurements were taken. Predictors of mortality were assessed using Cox proportional hazards models. Over the 18-y follow-up period, 151 deaths occurred (24%). In comparison with Yemenites, the adjusted hazard ratios (HR) for all cause mortality were HR = 1.77 [95% confidence interval (CI): 1.01-3.09] for Europeans/Americans; HR = 1.63 (95% CI: 0.89-2.99) for those from a Middle Eastern background; and HR = 1.56 (95% CI: 0.82-2.97) for North Africans. Mortality risk was 43% lower among those consuming > or =25 g of dietary fiber daily [HR = 0.57 (95% CI: 0.41-0.72)], and 42% lower for those consuming <300 mg/d of cholesterol [HR = 0.58 (95% CI: 0.34-0.96)]. Accumulating an average of 0.5 h/d of moderate physical activity reduced mortality by 47% [HR = 0.53 (95% CI: 0.29-0.97)]. Smoking, increased systolic BP, older age and male sex increased mortality risk. We conclude that in our study, although ethnic origin and lifestyle habits are interrelated, each affects mortality independently.     

MTHFR C677T genotype and cardiovascular risk in a general population without mandatory folic acid fortification

Purpose

Meta-analyses have suggested an effect of MTHFR C677T genotype (rs1801133), a proxy for blood total homocysteine, on cardiovascular disease (CVD) in populations with low population dietary folate. The aim was to examine the association and effect modification by serum folate and vitamin B12 levels between MTHFR and CVD-related outcomes in a general population with no mandatory folic acid fortification policy.

Methods

The study population included 13,748 adults retrieved from pooling of four population-based studies conducted in Denmark. MTHFR genotype, serum folate (measured in approximately 9,356 individuals), and serum vitamin B12 (9,215 individuals), hypertension, and dyslipidemia were measured at baseline, and participants were followed for a mean of 10.5–11.7 years in central registries for diagnoses of stroke (623 incidents), ischaemic heart disease (IHD) (835 incidents), and all-cause mortality (1,272 incidents).

Results

The MTHFR genotype (TT vs. CC/CT) was not associated with hypertension [OR (95 % CI) 1.09 (0.95–1.25)], dyslipidemia [OR (95 % CI) 0.97 (0.84–1.11)], stroke [HR (95 % CI) 0.92 (0.69–1.23)], and all-cause mortality [HR (95 % CI) 0.94 (0.77–1.14)], either overall, or in participants with low serum folate or B12 status (P values for interactions 0.15–0.94). Individuals with the MTHFR TT genotype had a higher risk of IHD (HR (95 % CI) 1.38 (1.11–1.71)), but this association was not modified by folate status (P value for interaction 0.45).

Conclusions

Our results do not support a causal relationship between homocysteine and CVD. However, we cannot exclude a direct causal effect of MTHFR C677T genotype on IHD.     

Association between Excessive Daytime Sleepiness and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis of Longitudinal Cohort Studies

ObjectiveExcessive daytime sleepiness (EDS) is a prevalent phenomenon in adults, and although cohort studies have reported an association between EDS and adverse health outcomes, the results are inconclusive. This meta-analysis summarizes the evidence from longitudinal cohort studies on the relationship between EDS and the risk of cardiovascular disease (CVD) or all-cause mortality.DesignA meta-analysis of prospective cohort studies was conducted.Setting and ParticipantsWe searched for relevant longitudinal cohort studies published through September 2019 using Web of Science, PubMed, Medline, and SciELO.MeasuresThe relative risk (RR) of EDS was pooled in random-effects or fixed-effects meta-analyses. Subgroup, sensitivity, and meta-regression analyses were performed to identify heterogeneous sources. Publication bias was assessed using the Begg and Egger tests.ResultsSeventeen studies (153,909 participants) were included. The mean follow-up was 5.4 (range, 2–13.8) years. The pooled relative risks of EDS were 1.28 [95% confidence interval (CI) 1.09–1.50] for total CVD events, 1.28 (95% CI 1.12–1.46) for coronary heart disease (CHD), 1.52 (95% CI 1.10–2.12) for stroke, 1.47 (95% CI 1.09–1.98) for CVD mortality, and 1.23 (95% CI 1.13–1.33) for all-cause mortality. Subgroup analyses by mean age, region, follow-up time, EDS assessment method, and year of publication yielded similar results.Conclusions and ImplicationsEDS is a modest but statistically significant predictor for CVD events, coronary heart disease, stroke, and CVD and all-cause mortality. However, its prognostic value warrants further investigation to identify those at highest risk of mortality and in need of intervention to improve outcomes.