Use of benzodiazepine and Z-drugs and mortality in older adults after myocardial infarction.

BACKGROUND: The adverse cardiovascular effects of benzodiazepines and Z-drugs (jointly referred as BZDRs) have been of concern. Yet, little is known about the use of BZDRs in relation to mortality risk among older adults with myocardial infarction history (post-MI). METHODS: This study is a secondary analysis of the Alpha Omega Cohort study, comprising post-MI patients aged 40-60 years. Self-reported information on the use of BZDRs, including types and dose, was collected at baseline. Four categories of mortality were examined, namely all-cause mortality, cardiovascular (CVD) mortality, cancer mortality, and non-CVD/non-cancer mortality. Associations between BZDRs use, by types and doses, and mortality were estimated with Cox regression models, adjusted for demographic and classic cardiovascular risk factors. RESULTS: A total of 433 (8.9%) out of 4837 (21.8% females) patients reported BZDRs use at baseline. During a median follow-up of 12.4 years, 2287 deaths were documented, of which 825 (36.1%) were due to CVD. BZDRs use was related to a statistically significantly higher risk of all-cause and CVD mortality; adjusted hazard ratios [95% CI] were (1.31 [1.41, 1.52]) and (1.43 [1.14, 1.81]), respectively. These relationships were dose-dependent-patients using BZDRs on an as-needed basis had similar risks compared to the non-uses, whereas patients with a daily use schedule and increasing doses had higher risks (p-value for trend: <0.001). CONCLUSION: BZDRs use was independently associated with a higher risk of all-cause and cardiovascular mortality in older post-MI patients, and there was evidence for a dose-dependent relationship. CLINICAL TRIAL REGISTRATION: NCT00127452 (www. CLINICALTRIALS: gov).

Dietary and Circulating Long-Chain Omega-3 Polyunsaturated Fatty Acids and Mortality Risk After Myocardial Infarction: A Long-Term Follow-Up of the Alpha Omega Cohort.

Background Habitual intake of long-chain omega-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid (EPA+DHA) from fish, has been associated with a lower risk of fatal coronary heart disease (CHD) in population-based studies. Whether that is also the case for patients with CHD is not yet clear. We studied the associations of dietary and circulating EPA+DHA and alpha-linolenic acid, a plant-derived omega-3 fatty acids, with long-term mortality risk after myocardial infarction. Methods and Results We analyzed data from 4067 Dutch patients with prior myocardial infarction aged 60 to 80 years (79% men, 86% on statins) enrolled in the Alpha Omega Cohort from 2002 to 2006 (baseline) and followed through 2018. Baseline intake of fish and omega-3 fatty acids were assessed through a validated 203-item food frequency questionnaire and circulating omega-3 fatty acids were assessed in plasma cholesteryl esters. Hazard ratios (HRs) with 95% CIs were obtained from Cox regression analyses. During a median follow-up period of 12 years, 1877 deaths occurred, of which 515 were from CHD and 834 from cardiovascular diseases. Dietary intake of EPA+DHA was significantly inversely associated with only CHD mortality (HR, 0.69 [0.52-0.90] for >200 versus ≤50 mg/d; HR, 0.92 [0.86-0.98] per 100 mg/d). Similar results were obtained for fish consumption (HRCHD, 0.74 [0.53-1.03] for >40 versus ≤5 g/d; Ptrend: 0.031). Circulating EPA+DHA was inversely associated with CHD mortality (HR, 0.71 [0.53-0.94] for >2.52% versus ≤1.29%; 0.85 [0.77-0.95] per 1-SD) and also with cardiovascular diseases and all-cause mortality. Dietary and circulating alpha-linolenic acid were not significantly associated with mortality end points. Conclusions In a cohort of Dutch patients with prior myocardial infarction, higher dietary and circulating EPA+DHA and fish intake were consistently associated with a lower CHD mortality risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03192410.

Physical activity and 4-year changes in body weight in 52,498 non-obese people: the Lifelines cohort.

OBJECTIVES: We investigated associations between leisure-time physical activity (LTPA) at different intensities (moderate and vigorous or moderate-to-vigorous) and prospective weight gain in non-obese people. We also examined whether these associations were independent of other lifestyle factors and changes in muscle mass and whether they were age-dependent and changed over a person's life course. METHODS: The data were extracted from the Lifelines cohort study (N = 52,498; 43.5% men) and excluded obese individuals (BMI > 30 kg/m2). We used the validated SQUASH questionnaire to estimate moderate-to-vigorous (MVPA; MET≥4), moderate (MPA; MET between 4 and 6.5) and vigorous PA (VPA; MET≥6.5). Body weight was objectively measured, and changes were standardized to a 4-year period. Separate analyses, adjusted for age, educational level, diet, smoking, alcohol consumption and changes in creatinine excretion (a marker of muscle mass), were performed for men and women. RESULTS: The average weight gain was + 0.45 ± 0.03 kg in women. Relative to each reference groups (No-MVPA, No-MPA and No-VPA), MVPA (Beta (95%CI): - 0.34 kg (- 0.56;-0.13)), MPA (- 0.32 kg (- 0.54;-0.10)) and VPA (- 0.30 kg (- 0.43;-0.18)) were associated with less gain in body weight in women after adjusting for potential confounders, described above. These associations were dose-dependent when physically active individuals were divided in tertiles. Beta-coefficients (95%CI) for the lowest, middle, and highest MVPA tertiles relative to the 'No-MVPA' were, respectively, - 0.24 (- 0.47;-0.02), - 0.31 (- 0.53;-0.08), and - 0.38 (- 0.61;-0.16) kg. The average weight gain in men was + 0.13 ± 0.03 kg, and only VPA, not MPA was associated with less body weight gain. Beta-coefficients (95%CI) for the VPA tertiles relative to the 'No-VPA' group were, respectively, - 0.25 (- 0.42;-0.09), - 0.19 (- 0.38;-0.01) and - 0.20 (- 0.38;-0.02) kg. However, after adjusting for potential confounders, the association was no longer significant in men. The potential benefits of leisure-time PA were age-stratified and mainly observed in younger adults (men < 35 years) or stronger with younger age (women < 55 years). CONCLUSION: Higher leisure-time MVPA, MPA, and VPA were associated with less weight gain in women < 55 years. In younger men (< 35 years), only VPA was associated with less weight gain.

Associations of Diet Quality and All-Cause Mortality Across Levels of Cardiometabolic Health and Disease: A 7.6-Year Prospective Analysis From the Dutch Lifelines Cohort.

OBJECTIVE: To simultaneously investigate the association of diet quality and all-cause mortality in groups with varying cardiometabolic diseases (CMDs) at baseline. RESEARCH DESIGN AND METHODS: From the population-based Lifelines cohort, 40,892 non-underweight participants aged ≥50 years with data on diet quality and confounding factors were included (enrollment 2006-2013). From food-frequency questionnaire data, tertiles of the Lifelines Diet Score were calculated (T1 = poorest, T3 = best diet quality). Four CMD categories were defined: 1) CMD free, 2) type 2 diabetes, 3) one cardiovascular disease (CVD), 4) two or more CMDs. Months when deaths occurred were obtained from municipal registries up until November 2019. Multivariable Cox proportional hazards models were applied for the total population and stratified by CMD categories. RESULTS: After a median follow-up of 7.6 years, 1,438 participants died. Diet quality and CMD categories were independently associated with all-cause mortality in crude and adjusted models (P < 0.001). A dose-response relationship of diet quality with all-cause mortality was observed in the total population (P trend < 0.001, T2 vs. T3 = 1.22 [1.07-1.41], T1 vs. T3 = 1.57 [1.37-1.80]). In stratified analyses, the association was significant for CMD-free individuals (T1 vs. T3 = 1.63 [1.38-1.93]) and for patients with type 2 diabetes (1.87 [1.17-3.00]) but not for patients with one CVD (1.39 [0.93-2.08]) or multiple CMDs (1.19 [0.80-1.76]). CONCLUSIONS: A high-quality diet can potentially lower all-cause mortality risk in the majority of the aging population. Its effect may be greatest for CMD-free individuals and patients with type 2 diabetes. Tailored dietary guidelines may be required for patients with extensive histories of CMDs.

Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes: Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants.

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction (p = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01-1.03, I2 = 61%) for total fish, 1.04 (1.01-1.07, I2 = 46%) for fatty fish, and 1.02 (1.00-1.04, I2 = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02-1.04, I2 = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.

Chronic bronchitis in the 50-year follow-up of the European cohorts of the Seven Countries Study: prevalence, mortality and association with cardiovascular diseases.

OBJECTIVES: To study prevalence of chronic bronchitis (CB) in residential populations and its relationship with mortality in a 50-year follow-up. MATERIAL AND METHODS: In the late 1950's-early 1960's, 7047 men aged 40-59 years were enrolled in 10 European cohorts of the Seven Countries Study (in Finland, the Netherlands, Italy, Serbia and Greece). After baseline examination, follow-up for mortality was extended during 50 years (45 year in the Serbian cohorts). Prevalence of CB, and 50-year mortality from CB and other major causes of death were used as end-points to identify their determinants using multivariate models. RESULTS: Prevalence of CB was directly associated with smoking habits and inversely associated with high socio-economic status (SES), forced expiratory volume in ¾ sec (FEV) and the ratio FEV/vital capacity (VC). Fifty-year mortality from CB was directly predicted by CB prevalence (from a minimum hazard ratio [HR] 2.35, 95% confidence limits [CI] 1.70-3.24, to a maximum HR 3.01, CI 2.18-5.20, depending on diagnostic criteria and different models) and age, and inversely by high SES, FEV and FEV/VC. The same applied in models predicting mortality from coronary heart disease (HR for prevalent CB: 1.53, CI 1.24-1.88), major cardiovascular diseases (HR 1.43, CI 1.23-1.67) and all-cause mortality (HR 1.48, CI 1.34-1.64) all adjusted for age, high SES, smoking habits and FEV. CONCLUSIONS: CB is strongly associated with major cardiovascular disease and all-cause mortality while FEV and FEV/VC seem to carry at least partly an independent role from CB in predicting long-term mortality.

Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions.

BACKGROUND: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies. OBJECTIVE: To examine the prospective associations of total and types of legume intake with the risk of incident T2D. METHODS: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity. RESULTS: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy. CONCLUSIONS: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.

The Mediterranean diet from past to future: Key concepts from the second "Ancel Keys" International Seminar.

The year 2020 celebrated the tenth anniversary of the recognition of the Mediterranean Diet as Intangible Cultural Heritage of Humanity by the UNESCO Intergovernmental Committee. This event represented a milestone in the history of nutrition, as the Mediterranean diet was the first traditional food practice to receive such award. Since then, a lot has been discussed not only on the beneficial aspects of the Mediterranean diet, but also on its complex role as a lifestyle model that includes a set of skills, knowledge and intercultural dialogue. This process ended up with the recognition in 2019 of Mediterranean diet as a possibly universal model of healthy diet from the EAT-Lancet Commission. These concepts were widely debated at the 2019 "Ancel Keys" International Seminar, held in Ascea (Italy) (for more information see: www.mediterraneandietseminar.org) with the aim to stimulate interest and awareness of a young group of participants on the current problems inherent to the effective implementation of the Mediterranean diet. The present article collects the contributions of several lecturers at the Seminar on key issues such as methodological and experimental approach, sustainability, molecular aspects in disease prevention, future exploitation, without neglecting a historical view of the Seven Countries Study. From the Seminar conclusions emerged a still vibrant and modern role of Mediterranean diet. The years to come will see national and international efforts to reduce the barriers that limit adherence to Mediterranean diet in order to plan for multi-factorial and targeted interventions that would guide our populations to a sustainable healthy living.

Nutrition beyond the first 1000 days: diet quality and 7-year change in BMI and overweight in 3-year old children from the Dutch GECKO Drenthe birth cohort.

The identification of early-life determinants of overweight is crucial to start early prevention. As weight gain accelerates between 2 and 6 years, we studied the association between diet quality in children aged 3 years and the change in BMI and overweight incidence in the following 7 years. From the Dutch GECKO Drenthe birth cohort, 1001 children born in 2006 or 2007 with complete data on diet (food frequency questionnaire at the age of 3 years) and growth at the age of 3 and 10 years were included. Diet quality was estimated with the evidence-based Lifelines Diet Score (LLDS). Measured height and weight at the age of 3 and 10 years were used to calculate BMI z-scores standardized for age and sex. The associations of the LLDS (in quintiles) with BMI-z change and overweight incidence were studied with linear and logistic regression analyses. Overweight prevalence in the total study population increased from 8.3% at the age of 3 years to 16.7% at the age of 10 years. The increase in overweight prevalence ranged from 14.7% in Q1 to 3.5% in Q5. Children with a better diet quality (higher quintiles of LLDS) increased significantly less in BMI-z (confounder adjusted ßLLDS = -0.064 (-0.101; -0.026)). Children with a poor diet quality at the age of 3 years had a considerably higher risk for overweight at the age of 10 years (confounder adjusted OR for Q1 vs. Q5 was 2.86 (95% CI 1.34-6.13). These results show the importance of diet in healthy development in the early life following the first 1000 days when new habits for a mature diet composed of food groups with lifelong importance are developed, providing a relevant window for overweight prevention early in life.

Association Between Depressive Symptoms and Incident Cardiovascular Diseases.

Importance: It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVDs). Objective: To characterize the association between depressive symptoms and CVD incidence across the spectrum of lower mood. Design, Setting, and Participants: A pooled analysis of individual-participant data from the Emerging Risk Factors Collaboration (ERFC; 162 036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and the UK Biobank (401 219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline. Exposures: Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Center for Epidemiological Studies Depression (CES-D) scale (range, 0-60; ≥16 indicates possible depressive disorder). The UK Biobank recorded the 2-item Patient Health Questionnaire 2 (PHQ-2; range, 0-6; ≥3 indicates possible depressive disorder). Main Outcomes and Measures: Primary outcomes were incident fatal or nonfatal coronary heart disease (CHD), stroke, and CVD (composite of the 2). Hazard ratios (HRs) per 1-SD higher log CES-D or PHQ-2 adjusted for age, sex, smoking, and diabetes were reported. Results: Among 162 036 participants from the ERFC (73%, women; mean age at baseline, 63 years [SD, 9 years]), 5078 CHD and 3932 stroke events were recorded (median follow-up, 9.5 years). Associations with CHD, stroke, and CVD were log linear. The HR per 1-SD higher depression score for CHD was 1.07 (95% CI, 1.03-1.11); stroke, 1.05 (95% CI, 1.01-1.10); and CVD, 1.06 (95% CI, 1.04-1.08). The corresponding incidence rates per 10 000 person-years of follow-up in the highest vs the lowest quintile of CES-D score (geometric mean CES-D score, 19 vs 1) were 36.3 vs 29.0 for CHD events, 28.0 vs 24.7 for stroke events, and 62.8 vs 53.5 for CVD events. Among 401 219 participants from the UK Biobank (55% were women, mean age at baseline, 56 years [SD, 8 years]), 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1 years). The HR per 1-SD higher depression score for CHD was 1.11 (95% CI, 1.08-1.14); stroke, 1.10 (95% CI, 1.06-1.14); and CVD, 1.10 (95% CI, 1.08-1.13). The corresponding incidence rates per 10 000 person-years of follow-up among individuals with PHQ-2 scores of 4 or higher vs 0 were 20.9 vs 14.2 for CHD events, 15.3 vs 10.2 for stroke events, and 36.2 vs 24.5 for CVD events. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors. Conclusions and Relevance: In a pooled analysis of 563 255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels lower than the threshold indicative of a depressive disorder. However, the magnitude of associations was modest.

Socio-economic disparities in the association of diet quality and type 2 diabetes incidence in the Dutch Lifelines cohort.

BACKGROUND: It is unknown whether a socio-economic difference exists in the association of diet quality with type 2 diabetes incidence, nor how diet influences the socioeconomic inequality in diabetes burden. METHODS: In 91,025 participants of the population-based Lifelines Cohort (aged ≥30, no diabetes or cardiovascular diseases at baseline), type 2 diabetes incidence was based on self-report, fasting glucose ≥ 7·0 mmol/l and/or HbA1c ≥ 6·5%. The evidence-based Lifelines Diet Score was calculated with data of a 110-item food frequency questionnaire. Socio-economic status (SES) was defined by educational level. Cox proportional hazards models were adjusted for age, gender, smoking, energy intake, alcohol intake and physical activity. FINDINGS: In 279,796 person-years of follow-up, 1045 diabetes cases were identified. Incidence rate was 5·7, 3·2 and 2·4 cases/1000 person-years in low, middle and high SES, respectively. Diet was associated with greater diabetes risk (HR(95%CI) in Q1 (poor diet quality) vs. Q5 (high diet quality) = 2·11 (1·70-2·62)). SES was a moderator of the association(pINTERACTION = 0·038). HRs for Q1 vs. Q5 were 1·66 (1·22-2·.27) in low, 2·76 (1·86-4·08) in middle and 2·46 (1·53-3·97) in high SES. With population attributable fractions of 14·8%, 40·1% and 37·3%, the expected number of cases/1000 person-years preventable by diet quality improvement was 0·85 in low, 1·28 in middle and 0·90 in high SES. INTERPRETATION: Diet quality improvement can potentially prevent one in three cases of type 2 diabetes, but because of a smaller impact in low SES, it will not narrow the socioeconomic health gap in diabetes burden. FUNDING: None.

Dietary protein intake and kidney function decline after myocardial infarction: the Alpha Omega Cohort.

BACKGROUND: Post-myocardial infarction (MI) patients have a doubled rate of kidney function decline compared with the general population. We investigated the extent to which high intake of total, animal and plant protein are risk factors for accelerated kidney function decline in older stable post-MI patients. METHODS: We analysed 2255 post-MI patients (aged 60-80 years, 80% men) of the Alpha Omega Cohort. Dietary data were collected with a biomarker-validated 203-item food frequency questionnaire. At baseline and 41 months, we estimated glomerular filtration rate based on the Chronic Kidney Disease Epidemiology Collaboration equations for serum cystatin C [estimated glomerular filtration rate (eGFRcysC)] alone and both creatinine and cystatin C (eGFRcr-cysC). RESULTS: Mean [standard deviation (SD)] baseline eGFRcysC and eGFRcr-cysC were 82 (20) and 79 (19) mL/min/1.73 m2. Of all patients, 16% were current smokers and 19% had diabetes. Mean (SD) total protein intake was 71 (19) g/day, of which two-thirds was animal and one-third plant protein. After multivariable adjustment, including age, sex, total energy intake, smoking, diabetes, systolic blood pressure, renin-angiotensin system blocking drugs and fat intake, each incremental total daily protein intake of 0.1 g/kg ideal body weight was associated with an additional annual eGFRcysC decline of -0.12 (95% confidence interval -0.19 to -0.04) mL/min/1.73 m2, and was similar for animal and plant protein. Patients with a daily total protein intake of ≥1.20 compared with <0.80 g/kg ideal body weight had a 2-fold faster annual eGFRcysC decline of -1.60 versus -0.84 mL/min/1.73 m2. Taking eGFRcr-cysC as outcome showed similar results. Strong linear associations were confirmed by restricted cubic spline analyses. CONCLUSION: A higher protein intake was significantly associated with a more rapid kidney function decline in post-MI patients.

Coronary heart disease mortality trends during 50 years as explained by risk factor changes: The European cohorts of the Seven Countries Study.

OBJECTIVES: The purpose of this study was to relate risk factor changes during decades with 50-year coronary heart disease mortality in European cohorts of middle-aged men of the Seven Countries Study. MATERIAL AND METHODS: In the 1950s-early 1960s, nine cohorts of 6518 men aged 40-59 years were examined in five European countries. Smoking habits, systolic blood pressure and serum cholesterol were measured at entry and five times during the next 35 years and a comprehensive Risk Factor Change Score was created. Coronary heart disease mortality data was collected during a 50-year follow-up, modelled by the Weibull distribution, whose shape (Weibull shape) was related to the Risk Factor Change Score by linear regression. RESULTS: The Risk Factor Change Score showed slight declines in the Finnish and Dutch cohorts, moderate or large increases in the other cohorts. These effects were related to a decrease of smoking habits in all cohorts, an increase of blood pressure in all cohorts except East Finland, a decrease of serum cholesterol in Finland and the Netherlands, whereas serum cholesterol increases were slight in Italy and large in Serbia and Greece. Weibull distribution shape for coronary heart disease mortality showed slight deceleration in one Finnish and the Dutch cohorts, large acceleration in the Serbian and Greek cohorts. The correlation coefficient of the Risk Factor Change Score versus Weibull shape for the nine cohorts was 0.78 (R2 = 0.60; p = 0.0132). CONCLUSIONS: Spontaneous long-term changes of major coronary risk factor levels were associated with changes in the same direction of coronary heart disease mortality risk modelled by the Weibull distribution, expressing a kind of 'natural experiment' with an outcome that matches those of controlled preventive trials.

Age- and Sex-Specific Analyses of Diet Quality and 4-Year Weight Change in Nonobese Adults Show Stronger Associations in Young Adulthood.

BACKGROUND: Although the general importance of diet quality in the prevention of unintentional weight gain is known, it is unknown whether its influence is age or sex dependent. OBJECTIVE: The aim of this study was to investigate whether the strength of the association between diet quality and 4-y weight change was modified by age and sex. METHODS: From the Dutch population-based Lifelines Cohort, 85,618 nonobese adult participants (age 18-93 y), recruited between 2006 and 2013, were included in the study. At baseline, diet was assessed with a 110-item food-frequency questionnaire. The Lifelines Diet Score, based on international evidence for diet-disease relations at the food group level, was calculated to assess diet quality. For analyses, the score was divided in quintiles (Qs). Body weight was objectively measured at baseline and after a median follow-up of 44 mo (25th-75th percentile: 35-51 mo). In between, body weight was self-reported twice. Linear mixed models were used to investigate the association between diet quality and weight change by sex and in 6 age categories (18-29, 30-39, 40-49, 50-59, 60-69, and ≥70 y). RESULTS: Mean 4-y weight change decreased over age categories. Confounder-adjusted linear mixed models showed that the association between diet quality and weight change was modified by sex (P-interaction = 0.001). In women, the association was also modified by age (P-interaction = 0.001). Poor diet quality was most strongly associated with weight gain in the youngest men [Q1 compared with Q5: +0.33 kg/y (95% CI: 0.10, 0.56)] and women [+0.22 kg/y (95% CI: 0.07, 0.37)]. In contrast, in women aged ≥70 y, poor diet quality was associated with greater weight loss [-0.44 kg/y (95% CI: -0.84, -0.05)]. CONCLUSIONS: Poor diet quality was related to higher weight gain, especially in young adults. Oppositely, among women aged ≥70 y, poor diet quality was related to higher weight loss. Therefore, a healthful diet is a promising target for undesirable weight changes in both directions.

Correction: Development of the food-based Lifelines Diet Score (LLDS) and its application in 129,369 Lifelines participants.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cardiovascular Risk Factors Associated With Venous Thromboembolism.

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Age at death of major cardiovascular diseases in 13 cohorts. The seven countries study of cardiovascular diseases 45-year follow-up.

OBJECTIVES: To explore age at death (AD) for major cardiovascular diseases (CVD) and their risk factors in originally middle-aged men followed nearly to extinction in the Seven Countries Study. MATERIALS AND METHODS: Thirteen cohorts of men aged 40-59 years (N = 10,628) in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) were enrolled in late 1950s and early 1960s and were followed 45 years for mortality. AD was computed for coronary heart disease (CHD), stroke (STR), heart disease of uncertain aetiology (HDUE) and for all-causes. AD was compared across CHD-HDUE-STR. Cox models were computed for each end-point using baseline age, cigarettes smoking, systolic blood pressure and serum cholesterol. RESULTS: After 45 years 92.9% of men had died. The most common CVD death was CHD in most cohorts except some Mediterranean and Japanese cohorts where STR or HDUE were most prevalent. In 13 cohorts mean AD was 74.5, 73.5, 75.7 and 79.1 years, respectively, for all-cause, CHD, STR and HDUE mortality (all possible differences were significant). The difference, across cohorts, between the highest and the lowest mean AD was 12.9, 9.0 and 4.7 years for CHD, HDUE and STR mortality, respectively. Risk factors explored were significant predictors of all three CVD end-points, except serum cholesterol, specific to CHD mortality. CONCLUSIONS: AD is a useful indicator of previous health and aging populations. STR and HDUE are diseases appearing later in life, thus being associated with a higher AD compared with CHD mortality.

Cardiovascular Risk Factors Accelerate Kidney Function Decline in Post-Myocardial Infarction Patients: The Alpha Omega Cohort Study.

INTRODUCTION: Impaired kidney function is a robust risk factor for cardiovascular mortality. Age-related annual kidney function decline of 1.0 ml/min per 1.73 m2 after age 40 years is doubled in post-myocardial infarction (MI) patients. METHODS: We investigated the impact of the number of cardiovascular risk factors (including unhealthy lifestyle) on annual kidney function decline, in 2426 post-MI patients (60-80 years) of the prospective Alpha Omega Cohort study. Glomerular filtration rate was estimated by serum cystatin C (eGFRcysC) and combined creatinine-cystatin C (eGFRcr-cysC), using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations from 2012. Data were analyzed by multivariable linear and logistic regression. RESULTS: At baseline, mean (SD) eGFRcysC and eGFRcr-cysC were 81.5 (19.6) and 78.5 (18.7) ml/min per 1.73 m2, respectively. Of all patients, 79% were men, 19% had diabetes, 56% had high blood pressure (≥140/90 mm Hg), 16% were current smokers, 56% had high serum low-density lipoprotein (LDL of ≥2.5 mmol/l), and 23% were obese (body mass index of ≥30.0 kg/m2). After multivariable adjustment, the additional annual eGFRcysC decline (95% confidence interval) was as follows: in patients with versus without diabetes, -0.90 (-1.23 to -0.57) ml/min per 1.73 m2; in patients with high versus normal blood pressure, -0.50 (-0.76 to -0.24) ml/min per 1.73 m2; in obese versus nonobese patients, -0.31 (-0.61 to 0.01) ml/min per 1.73 m2; and in current smokers versus nonsmokers, -0.19 (-0.54 to 0.16) ml/min per 1.73 m2. High LDL was not associated with accelerated eGFRcysC decline. Similar results were obtained with eGFRcr-cysC. CONCLUSION: In older, stable post-MI patients without cardiovascular risk factors, the annual kidney function decline was -0.90 (-1.16 to -0.65) ml/min per 1.73 m2. In contrast, in post-MI patients with ≥3 cardiovascular risk factors, the annual kidney function decline was 2.5-fold faster, at -2.37 (-2.85 to -1.89) ml/min per 1.73 m2.