Alpha Omega Cohort Research Articles

Vitamin D status, physical activity and long-term mortality risk after myocardial infarction: a prospective analysis in the Alpha Omega Cohort.

In post-myocardial infarction (MI) patients, we examined independent and combined associations of vitamin D status and physical activity (PA) with long-term mortality, including effect modification by health determinants. We conducted a prospective analysis of 4,837 MI patients from the Alpha Omega Cohort. Baseline blood samples (2002-2006) were assessed for plasma 25-hydroxyvitamin D (25[OH]D) levels using LC-MS/MS. PA was assessed using a validated questionnaire. Patients were followed for mortality through December 2022. HRs for CVD and all-cause mortality were obtained across sex-specific tertiles of 25(OH)D and four categories of PA using Cox models, adjusted for sociodemographic and lifestyle factors. Potential effect modification by health determinants was examined through stratification. Patients were 69±5.6 years old, 78% was male, 21% had diabetes, and 10% used vitamin D-containing supplements. Over 14.4 years, 3,206 deaths occurred, including 1,244 from CVD. Median 25(OH)D was 21.1 ng/mL and 44% was vitamin D deficient (<20 ng/mL). Higher 25(OH)D levels were associated with lower CVD (HR:0.63, 95%CI:0.54,0.74) and all-cause mortality (HR:0.68, 95%CI:0.62,0.75). For PA levels (high vs. light), HRs were 0.72 (95%CI:0.61,0.85) for CVD mortality and 0.83 (95%CI:0.75,0.92) for all-cause mortality. Patients with low 25(OH)D and no PA had a threefold higher mortality risk than those with high 25(OH)D levels and high PA. The associations were not significantly modified by sex, comorbidities and other health determinants. Vitamin D status and PA were inversely and independently associated with long-term risk of CVD and all-cause mortality after MI, regardless of other health determinants.

Dietary and genetic determinants of non-alcoholic fatty liver disease in coronary heart disease patients.

A healthy diet reduces the risk of non-alcoholic fatty liver disease (NAFLD) in the general population, especially in individuals who are genetically predisposed to NAFLD. Little is known in patients who suffered from a myocardial infarction (MI). We examined the interaction between diet quality and genetic predisposition in relation to NAFLD in post-MI patients. We included 3437 post-MI patients from the Alpha Omega Cohort. Diet quality was assessed with adherence to the Dutch Healthy Diet index 2015 (DHD15-index). A weighted genetic risk score (GRS) for NAFLD was computed using 39 genetic variants. NAFLD prevalence was predicted using the Fatty Liver Index. Prevalence ratios (PR) with 95% confidence intervals of DHD15-index and GRS in relation to NAFLD were obtained with multivariable Cox proportional hazards models. The interaction between DHD15-index and GRS in relation to NAFLD was assessed on an additive and multiplicative scale. Patients had a mean age of 69 (± 5.5) years, 77% was male and 20% had diabetes. The DHD15-index ranged from 28 to 120 with a mean of 73. Patients with higher diet quality were less likely to suffer from NAFLD, with a PR of 0.76 (0.62, 0.92) for the upper vs lower quintile of DHD15-index. No association between the GRS and NAFLD prevalence was found (PR of 0.92 [0.76, 1.11]). No statistically significant interaction between the DHD15-index and GRS was observed. In Dutch post-MI patients, adherence to the Dutch dietary guidelines was associated with a lower prevalence of NAFLD, as assessed by the FLI. This association was present regardless of genetic predisposition in this older aged cohort.

Association of body mass index and waist circumference with long-term mortality risk in 10,370 coronary patients and potential modification by lifestyle and health determinants.

Body adiposity is known to affect mortality risk in patients with coronary artery disease (CAD). We examined associations of body mass index (BMI) and waist circumference (WC) with long term mortality in Dutch CAD patients, and potential and effect modification of these associations by lifestyle and health determinants. 10,370 CAD patients (mean age ∼65 y; 20% female; >80% on cardiovascular drugs) from the prospective Alpha Omega Cohort and Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease study were included. Cox models were used to estimate categorical and continuous associations (using restricted cubic splines) of measured BMI and WC with all-cause and cardiovascular mortality risk, adjusting for age, sex, smoking, alcohol, physical activity and educational level. Analyses were repeated in subgroups of lifestyle factors (smoking, physical activity, diet quality), education and health determinants (diabetes, self-rated health). During ∼10 years of follow-up (91,947 person-years), 3,553 deaths occurred, including 1,620 from cardiovascular disease. U-shaped relationships were found for BMI and mortality risk, with the lowest risk for overweight patients (BMI ∼27 kg/m2). For obesity (BMI ≥30), the HR for all-cause mortality was 1.31 (95% CI: 1.11, 1.41) in male patients and 1.10 (95% CI: 0.92, 1.30) in female patients, compared to BMI 25-30 kg/m2. WC was also non-linearly associated with mortality, and HRs were 1.18 (95%CI:1.06, 1.30) in males and 1.31 (95%CI:1.05, 1.64) in females for the highest vs. middle category of WC. Results for cardiovascular mortality were mostly in line with the results for all-cause mortality. U-shaped associations were found in most subgroups, associations were moderately modified by physical activity, smoking and educational level. CAD patients with obesity and a large WC were at increased risk of long-term CVD and all-cause mortality, while mildly overweight patients had the lowest risk. These associations were consistent across subgroups of patients with different lifestyles and health status.

The Beverage Quality Index and risk of cardiometabolic outcomes after a myocardial infarction: A prospective analysis in the Alpha Omega Cohort

Background and aimsIndividual beverages have varying associations with cardiometabolic outcomes, but little is known about overall beverage quality and cardiometabolic risk after myocardial infarction (MI). We created the Beverage Quality Index (BQI) to assess beverage quality and examined its association with cardiometabolic outcomes after MI. Methods and resultsWe included 4365 Dutch post-MI patients from the Alpha Omega Cohort, aged 60–80 years. Diet was assessed at baseline (2002–2006) with a 203-item FFQ. The BQI included eight components (coffee, tea, milk, juices, sugar-sweetened beverages, alcohol, added sugar to coffee and tea, and energy from beverages), and ranged from 0 to 80. Multivariable Cox models were used to estimate HRs for the BQI in relation to incident diabetes mellitus (DM), major adverse cardiovascular events (MACE), recurrent cardiovascular disease (CVD) and fatal CVD over 3.4 y of follow-up, with follow-up for fatal CVD extended through 2018 (12.4 y). The average BQI was 50.0 ± 12.5. During 3.4 y of follow-up, we identified 186 incident cases of DM, 601 of MACE, 310 of recurrent CVD and 140 of fatal CVD. In multivariable models, a higher BQI (T3 vs. T1) was associated with lower risk of MACE [HR: 0.73 (0.59–0.90)], and recurrent CVD [HR: 0.67 (0.50–0.91)], but not with DM or CVD mortality. After 12.4 y of follow-up, 903 CVD deaths occurred. A significant inverse association with CVD mortality during long-term follow-up was found [HR: 0.81 (0.68–0.96)]. ConclusionOverall beverage intake quality, as assessed by the BQI, may represent an important target for the prevention of recurrent CVD.

Diet quality in relation to kidney function and its potential interaction with genetic risk of kidney disease among Dutch post-myocardial infarction patients

PurposeWe examined the relation between diet quality, its components and kidney function decline in post-myocardial infarction (MI) patients, and we explored differences by genetic risk of chronic kidney disease (CKD).MethodsWe analysed 2169 patients from the Alpha Omega Cohort (aged 60–80 years, 81% male). Dietary intake was assessed at baseline (2002–2006) using a validated food-frequency questionnaire and diet quality was defined using the Dutch Healthy Diet Cardiovascular Disease (DHD-CVD) index. We calculated 40-months change in estimated glomerular filtration rate (eGFR, mL/min per 1.73m2). We constructed a weighted genetic risk score (GRS) for CKD using 88 single nucleotide polymorphisms previously linked to CKD. Betas with 95%-confidence intervals (CIs) were obtained using multivariable linear regression models for the association between DHD-CVD index and its components and eGFR change, by GRS.ResultsThe average DHD-CVD index was 79 (SD 15) points and annual eGFR decline was 1.71 (SD 3.86) mL/min per 1.73 m2. The DHD-CVD index was not associated with annual eGFR change (per 1-SD increment in adherence score: -0.09 [95% CI -0.26,0.08]). Results for adherence to guidelines for red meat showed less annual eGFR decline (per 1-SD: 0.21 [0.04,0.38]), whereas more annual eGFR decline was found for legumes and dairy (per 1-SD: -0.20legumes [-0.37,-0.04] and − 0.18dairy [-0.34,-0.01]). Generally similar results were obtained in strata of GRS.ConclusionThe DHD-CVD index for overall adherence to Dutch dietary guidelines for CVD patients was not associated with kidney function decline after MI, irrespective of genetic CKD risk. The preferred dietary pattern for CKD prevention in CVD patients warrants further research.

Diet quality and long-term cardiovascular mortality after myocardial infarction in the Alpha Omega Cohort

Abstract Introduction A healthy diet is important for the prevention and treatment of cardiovascular disease (CVD). The Dutch Health Council recently defined dietary guidelines for patients with atherosclerotic CVD (ASCVD), which we investigated in relation to long-term mortality after myocardial infarction (MI). Purpose We developed the Dutch Healthy Diet index for CVD patients (DHD-CVD index) and examined its relation with mortality in post-MI patients. Methods We included 4,365 patients of the Dutch Alpha Omega Cohort (60-80 y, 80% male) with a MI &amp;lt;10 y prior to study enrolment. Dietary intake was assessed at baseline (2002-2006), using a validated 203-item food frequency questionnaire. To create the DHD-CVD index, the existing 2015 Dutch Healthy Diet index was adapted using the 2023 Dutch dietary guidelines for ASCVD patients (scale from 0 to maximal adherence [0-150]). Patients were followed for cause-specific mortality through December 2018. Hazard Ratios (HRs) across quartiles of the DHD-CVD-index (ref = Q1, i.e. low overall diet quality) and per 1-SD increment in score were estimated using Cox proportional hazard models. Associations were adjusted for age, sex, total energy intake, smoking, education and physical activity. Results were additionally stratified for sex, obesity and diabetes. Results Of the cohort, 17% smoked, 21% had diabetes and &amp;gt;90% used statins or other CVD drugs. During a follow-up of 48,660 person-years, 2,048 deaths occurred of which 911 were due to CVD. The mean DHD-CVD score was 78.9 (SD 13) points. High diet quality (Q4) was associated with a 29% lower risk of CVD mortality compared to low diet quality (HR: 0.71, 95% CI: 0.56, 0.84), with an HR of 0.88 (95% CI: 0.82, 0.94) per 1-SD. For all-cause mortality, we observed a 14% lower risk for high vs. low diet quality (HR: 0.86, 95% CI: 0.76, 0.98), with an HR of 0.94 (95% CI: 0.90, 0.98) per 1-SD. HRs did not essentially differ between male of female patients, or between obese and non-obese patients. HRs for CVD mortality were stronger in non-diabetic patients (HR: 0.86, 95% CI: 0.79, 0.93; per 1-SD), and no longer statistically significant in patients with diabetes (HR: 0.97, 95% CI: 0.84, 1.11; per 1-SD). Conclusion A high diet quality, measured with the DHD-CVD index, was associated with a lower risk of CVD and all-cause mortality after MI in Dutch patients. Adherence to dietary guidelines for CVD patients should be considered on top of medication use.

Vitamin D status and 12-year mortality risk after myocardial infarction

Abstract Introduction Vitamin D deficiency has been associated with an increased risk of cardiovascular disease (CVD) mortality in healthy populations. Whether this association is also present in patients with established CVD is not yet clear. Purpose We examined the association of serum 25-hydroxyvitamin D [25(OH)D] as an indicator of vitamin D status with 12-year risk of CVD and all-cause mortality in post-myocardial infarction (MI) patients. Methods A prospective analysis was carried out in 4,479 Dutch patients from the Alpha Omega Cohort (aged 60-80 y) who had an MI ≤10 y prior to study enrolment. Non-fasting venous blood was sampled at baseline (2002-2006) for the assessment of 25(OH)D using LC-MS/MS. Patients were followed for cause-specific mortality through December 2018. Hazard ratios (HRs) for CVD and all-cause mortality were obtained in sex-specific 25(OH)D tertiles using Cox regression models, adjusted for age, education, physical activity, smoking status, alcohol intake, adherence to dietary guidelines (i.e. 2015 Dutch Healthy Diet index [DHD15]), prevalent diabetes and kidney function (eGFR). Restricted cubic splines (RCS) analysis was performed for continuous associations, using median 25(OH)D as the reference. Results Patients were 69.0 ± 5.6 y old, 78% was male, 17% were current smokers, 18% had diabetes and 8% used vitamin-D containing supplements. A total of 2,091 deaths occurred during a median follow-up period of 12.4 y (49,529 person-years), including 924 from CVD as a primary or contributing cause. Median 25(OH)D was 21.3 ng/mL, and tertile cut-offs were 18.3 and 26.2 ng/mL for males and 15.2 and 22.0 ng/mL for females. Of the cohort, 44% were vitamin D deficient (&amp;lt;20 ng/mL). Lower risks of CVD mortality were observed in the mid tertile (HR: 0.76, 95%CI:0.65-0.88) and upper tertile (HR: 0.67, 95%CI:0.57-0.79) of 25(OH)D, compared to the lower tertile. RCS showed a roughly linear association (P-non-linearity = 0.08), with a 11% lower risk of CVD mortality per 5 ng/mL-increment in 25(OH)D (HR: 0.89, 95%CI: 0.86-0.93). Inverse associations were more pronounced in patients with a higher calcium intake (&amp;gt;845 g/d; 0.87, 95%CI:0.96-0.98; per 5 ng/mL) and in patients who were more physically active (HR: 0.88, 95%CI: 0.83-0.93; per 5 ng/mL). Exclusion of 378 vitamin D supplement users did not materially change the associations. For all-cause mortality, multivariable HRs were 0.74 (95%CI: 0.67-0.82) in the mid tertile, and 0.65 (95%CI: 0.58-0.73) in the upper tertile, compared to the lower tertile. Conclusion A low vitamin D serum concentration is related to a higher risk of recurrent CVD and all-cause mortality in patients with coronary artery disease. Causality remains to be determined preferably in a clinical trial to evaluate the effect of oral suppletion of vitamin D on recurrent CVD and mortality risk in these patients.

Serum uric acid is related to liver and kidney disease and 12-year mortality risk after myocardial infarction.

To study the associations of non-alcoholic fatty liver disease (NAFLD), chronic kidney disease (CKD), and serum uric acid (SUA) in patients with post-myocardial infarction (MI) patients, and the relationship of SUA with 12-year mortality risk. We included 3,396 patients (60-80 years old, 78% men) of the Alpha Omega Cohort. Multivariable prevalence ratios (PRs) were obtained for the association of NAFLD [fatty liver index (FLI), ≥77 (women) and ≥79 (men)] with CKD [estimated glomerular filtration rate (eGFR), <60 mL/min per 1.73 m2]. We calculated sensitivity and specificity of SUA to detect the (combined) presence and absence of NAFLD and CKD. Cause-specific mortality was monitored from enrolment (2002-2006) through December 2018. Hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality in SUA categories were obtained from multivariable Cox models. Median baseline FLI was 67 (men, 68; women, 64), and mean ± SD eGFR was 81 ± 20 mL/min per 1.73 m2 (17% with CKD). Sex-specific FLI was associated with higher CKD prevalence (PRtertile3 vs. tertile1, 1.94; 95% confidence interval: 1.57, 2.39). Baseline SUA was 0.36 ± 0.09 mmol/L. With increasing SUA concentrations, specificity for the presence of NAFLD, CKD, or both increased, and sensitivity decreased. During 12 (interquartile range, 9-14) years of follow-up, 1,592 patients died (713 from CVD). HRs ranged from 1.08 (0.88, 1.32) for SUA ≤0.25 mmol/L to 2.13 (1.75, 2.60) for SUA >0.50 mmol/L vs. SUA >0.30-0.35 mmol/L for all-cause mortality. For CVD mortality, HRs ranged from 1.05 (0.77, 1.44) to 2.43 (1.83, 3.25). NAFLD and CKD were strongly associated, which was reflected by higher SUA concentrations. SUA was a strong predictor of 12-year mortality risk after MI.

Fatty Liver Index and mortality after myocardial infarction: A prospective analysis in the Alpha Omega Cohort.

Accumulating evidence shows that NAFLD might play a role in the etiology and progression of CVD, but little is known on the association of NAFLD and CVD mortality in patients with a history of a myocardial infarction (MI). Therefore, we studied the relationship of Fatty Liver Index (FLI), as indicator for non-alcoholic fatty liver disease (NAFLD), with 12-year risk of cardiovascular disease (CVD) and all-cause mortality in post-MI patients. We included 4165 Dutch patients from the Alpha Omega Cohort aged 60-80 years who had an MI ≤10 years prior to study enrolment. NAFLD was defined as FLI ≥60. Patients were followed for cause-specific mortality from enrolment (2002-2006) through December 2018. Hazard ratios for CVD and all-cause mortality were obtained by multivariable Cox regression using FLI <30 (indicating absence of NAFLD) as the reference. Baseline FLI as a continuous measure was studied with mortality using restricted cubic splines analyses. The median (IQR) FLI was 68 (48-84). Sixty percent of the patients had FLI ≥60, who were more likely to be male and more often had diabetes, high blood pressure, and high serum cholesterol levels. During 12 years of follow-up, 2042 deaths occurred of which 846 from CVD. Patients with NAFLD were at increased risk of CVD mortality (HR: 1.55 [1.19, 2.03]) and all-cause mortality (HR: 1.21 [1.03; 1.41]) compared to patients without NAFLD. Results remained consistent after excluding patients with obesity and diabetes. To conclude, the adverse association of FLI with CVD mortality was stronger in female than in male patients with conventional cut-off points. FLI ≥60, indicating NAFLD, was a predictor for CVD and all-cause mortality in post-MI patients, independent of other cardiometabolic risk factors. However, cut-off points might differ between male and female patients for predicting CVD mortality.

Compliance with the DASH diet and risk of all-cause and cardiovascular mortality in patients with myocardial infarction

The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to effectively reduce blood pressure and body weight, but its effectiveness for reducing (cardiovascular) mortality rates has never been assessed in a clinical trial. Causal effects of dietary interventions are difficult to measure, due to practical limitations of randomized controlled diet trials. Target trial emulation can be used to improve causal inference in observational data. The aim of this study was to emulate a target trial assessing the relationship between compliance with the DASH diet and cardiovascular and all-cause mortality risk in patients with established CVD. Using data from the Alpha Omega Cohort, we emulated a DASH diet trial in patients with a history of myocardial infarction (MI). Inverse probability of treatment weighting (IPTW) was used to balance confounders over DASH-compliant and non-DASH-compliant participants. Hazard ratios (HRs) were estimated with IPT-weighted Cox models. Of 4365 patients (79% male, median age 69 years, >80% treated with lipid- and blood pressure-lowering medication), 598 were classified as DASH-compliant (compliance score ≥5 out of 9). During a median follow-up of 12.4 years, 2035 deaths occurred of which 903 (44%) were of cardiovascular origin. DASH compliance was not associated with all-cause mortality (HR 0.92, 95%CI 0.0.80-1.06) and cardiovascular mortality (HR 0.90, 95%CI 0.72-1.11). In an emulated target trial on the DASH diet in the Alpha Omega cohort no relation was found between DASH compliance and risk of all-cause and cardiovascular mortality in patients with a history of MI. The DASH diet's effects may have been modified in this population by concomitant use of blood pressure-lowering medications.

Sugar and low/no-calorie-sweetened beverage consumption and associations with body weight and waist circumference changes in five European cohort studies: the SWEET project

PurposeResults of prospective studies investigating associations between low/no-calorie sweeteners (LNCS) and body weight-related outcomes are inconclusive. We conducted dose–response and theoretical replacement individual patient data meta-analyses using harmonised prospective data to evaluate associations between sugar-sweetened beverage (SSB) consumption, low/no-calorie sweetened beverage (LNCB) consumption, and changes in body weight and waist circumference.MethodsIndividual participant data were obtained from five European studies, i.e., Lifelines Cohort Study, NQplus study, Alpha Omega Cohort, Predimed-Plus study, and Feel4diabetes study, including 82,719 adults aged 18–89 with follow-up between 1 and 9 years. Consumption of SSB and LNCB was assessed using food-frequency questionnaires. Multiple regression analyses adjusting for major confounders and including substitution models were conducted to quantify associations in individual cohorts; random-effects meta-analyses were performed to pool individual estimates.ResultsOverall, pooled results showed weak adverse associations between SSB consumption and changes in body weight (+ 0.02 kg/y, 95%CI 0.00; 0.04) and waist circumference (+ 0.03 cm/y, 95%CI 0.01; 0.05). LNCB consumption was associated with higher weight gain (+ 0.06 kg/y, 95%CI 0.04; 0.08) but not with waist circumference. No clear associations were observed for any theoretical replacements, i.e., LNCB or water for SSB or water for LNCB.ConclusionIn conclusion, this analysis of five European studies found a weak positive association between SSB consumption and weight and waist change, whilst LNCB consumption was associated with weight change only. Theoretical substitutions did not show any clear association. Thus, the benefit of LNCBs as an alternative to SSBs remains unclear.

P10-031-23 Taste-Related Genes Are Differentially Associated With Food Group Intakes Among Dutch Adults: A Cross-Sectional Analysis in the Alpha Omega Cohort

P10-031-23 Taste-Related Genes Are Differentially Associated With Food Group Intakes Among Dutch Adults: A Cross-Sectional Analysis in the Alpha Omega Cohort

Dairy products and kidney function decline after myocardial infarction: A prospective analysis in the Alpha Omega Cohort

Population-based studies have shown both beneficial and neutral associations between dairy consumption and kidney function outcomes. We investigated the association between dairy products and kidney function decline in drug-treated post-myocardial infarction (MI) patients. We analysed data of 2169 post-MI patients (aged 60-80 years, 81% male) of the Alpha Omega Cohort. Dietary data were collected at baseline (2002-2006) using a validated 203-item food frequency questionnaire. The 2021 Chronic Kidney Disease Epidemiology (CKD-EPI) equation was used to estimate 40-months change in creatinine-cystatin C based glomerular filtration rate (eGFRcr-cysC, mL/min per 1.73m2). Beta coefficients and 95% confidence intervals (CIs) for dairy products in relation to annual eGFRcr-cysC change were obtained from multivariable linear regression, adjusted for age, sex, energy intake, and other lifestyle and dietary factors. Baseline energy-adjusted median intakes were 64g/day for total milk, 20g/day for hard cheeses, 18g/day for plain yogurt, and 70g/day for dairy desserts. Mean±SD eGFRcr-cysC was 84±20 (13% with CKD), and annual eGFRcr-cysC change was-1.71±3.85. In multivariable models, high vs. low intakes of total milk, cheese, and dairy desserts were not associated with annual eGFRcr-cysC change (βtotal milk:-0.21 [-0.60; 0.19], βcheese:-0.08 [-0.52; 0.36], βdairy desserts:-0.24 [-0.72; 0.24]). High vs. low intake of yogurt was adversely associated with annual eGFRcr-cysC change (βtotal yogurt:-0.50 [-0.91;-0.09]), but subsequent spline analyses showed no clear dose-response association. Intakes of milk, cheese or dairy desserts were not associated with a delayed kidney function decline after MI. The observed adverse association for yogurt should be interpreted with caution. Our findings require confirmation in other cohorts of coronary heart disease patients.

Sugar-sweetened beverages, low/no-calorie beverages, fruit juice and non-alcoholic fatty liver disease defined by fatty liver index: the SWEET project

BackgroundSweetened beverage intake may play a role in non-alcoholic fatty liver disease (NAFLD) development, but scientific evidence on their role is limited. This study examined associations between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB) and fruit juice (FJ) intakes and NAFLD in four European studies.MethodsData for 42,024 participants of Lifelines Cohort, NQPlus, PREDIMED-Plus and Alpha Omega Cohort were cross-sectionally analysed. NAFLD was assessed using Fatty Liver Index (FLI) (≥60). Restricted cubic spline analyses were used to visualize dose–response associations in Lifelines Cohort. Cox proportional hazard regression analyses with robust variance were performed for associations in individual cohorts; data were pooled using random effects meta-analysis. Models were adjusted for demographic, lifestyle, and other dietary factors.ResultsEach additional serving of SSB per day was associated with a 7% higher FLI-defined NAFLD prevalence (95%CI 1.03–1.11). For LNCB, restricted cubic spline analysis showed a nonlinear association with FLI-defined NAFLD, with the association getting stronger when consuming ≤1 serving/day and levelling off at higher intake levels. Pooled Cox analysis showed that intake of >2 LNCB servings/week was positively associated with FLI-defined NAFLD (PR 1.38, 95% CI 1.15–1.61; reference: non-consumers). An inverse association was observed for FJ intake of ≤2 servings/week (PR 0.92, 95% CI: 0.88–0.97; reference: non-consumers), but not at higher intake levels. Theoretical replacement of SSB with FJ showed no significant association with FLI-defined NAFLD prevalence (PR 0.97, 95% CI 0.95–1.00), whereas an adverse association was observed when SSB was replaced with LNCB (PR 1.12, 95% CI 1.03–1.21).ConclusionsPooling results of this study showed that SSB and LNCB were positively associated with FLI-defined NAFLD prevalence. Theoretical replacement of SSB with LNCB was associated with higher FLI-defined NAFLD prevalence. An inverse association was observed between moderate intake of FJ and FLI-defined NAFLD. Our results should be interpreted with caution as reverse causality cannot be ruled out.

Abstract MP25: Circulating Odd-Chain Fatty Acids and Mortality Risk After Myocardial Infarction in the Alpha Omega Cohort

Background: Circulating odd-chain fatty acids (OCFAs) 15:0 and 17:0, potential biomarkers of dairy (fat) intake, have been associated with cardiometabolic outcomes in population-based studies. Whether circulating OCFAs are related to mortality risk in patients who experienced a myocardial infarction (MI) is not yet clear. Methods: We included 4,741 Dutch patients aged 60-80 y (78% males) from the Alpha Omega Cohort, who experienced a myocardial infarction (MI) up to 10 years prior to study enrolment. At baseline (2002-2006), data were obtained on risk factors for cardiovascular disease (CVD), medication, lifestyle factors and dietary intakes (203-item FFQ). Fatty acids in serum cholesteryl esters (CE) were assessed using gas chromatography. Multivariable Cox models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CI) for total and CVD mortality in relation to 15:0 and 17:0 in CE (per 10 th to 90 th percentile range, P 10-90 ). HRs were adjusted for age, sex, education, BMI, physical activity, diabetes, other CVD risk factors, medication, circulating linoleic acid, circulating EPA+DHA, and dietary factors. Missing data imputation was performed for confounders. Findings: Most patients used cardiovascular drugs (statins: 85%) and 979 patients (21%) had diabetes. During a median follow-up period of 12.4 years (total of 52,625 person-years), 2,233 patients died, of whom 984 from CVD. Circulating levels (% of total fatty acids) were low for 15:0 (median: 0.16; P 10-90 : 0.11-0.21) and 17:0 (median: 0.08; P 10-90 : 0.00-0.11). For 15:0, age and sex adjusted HRs per P 10-90 were 0.88 (95% CI: 0.81-0.95; P =0.001) for total mortality and 0.94 (0.83-1.06) for CVD mortality. In the most adjusted model, HRs for 15:0 were 0.92 (0.84-1.00; P =0.042) and 0.97 (0.85-1.11), respectively. For 17:0, HRs were 0.94 (0.85-1.05) for total mortality and 0.97 (0.83-1.13) for CVD mortality. Stratified analyses by sex showed inverse associations for 15:0 mainly in men (total mortality: HR of 0.90 [0.82-1.00]; P =0.047). For 17:0, inverse but non-significant associations were mainly observed in women (total mortality: HR of 0.85 [0.68-1.05]). Associations for 17:0, but not for 15:0, were stronger in diabetic patients (total mortality: HR of 0.78 [0.64-0.96]; P =0.019). Conclusions: Higher circulating OCFA levels may be related to a lower mortality risk after MI, which needs confirmation in other cohorts of CVD patients. The role of dairy fat intake in this relationship warrants further investigation.

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

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). This study is a secondary analysis of the Alpha Omega Cohort study, comprising post-MI patients aged 40-60years. 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. A total of 433 (8.9%) out of 4837 (21.8% females) patients reported BZDRs use at baseline. During a median follow-up of 12.4years, 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). 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. NCT00127452 (www. gov).

Effect of diet and lifestyle on the relationship between body mass index and waist circumference and cardiovascular mortality in myocardial infarction patients from the Alpha Omega Cohort

Abstract Introduction The associations between measures of body adiposity body mass index (BMI) and waist circumference (WC) and cardiovascular disease (CVD) mortality have been frequently studied and usually follow a J-shaped curve or show a positive relationship. However, less is known about the influence of diet and physical activity on these associations. Purpose We aimed to gain insight in potential lifestyle-related effect modifiers of the association of BMI and WC with CVD mortality in myocardial infarction (MI) patients. Methods We included 4,837 Dutch patients from the Alpha Omega Cohort with a MI &amp;lt;10 y prior enrolment. BMI and WC were assessed at baseline (2002–2006). Patients were followed through December 2018 for vital status and cause-specific mortality. Continuous associations of BMI and WC with CVD mortality were estimated using Cox proportional hazards models with restricted cubic splines. A BMI of 25 kg/m2 and a WC of 100 cm were used as the references. Age and sex adjusted associations were stratified for diet quality and physical activity level and interaction terms were calculated. Results Of the study population (69.0±5.6 y), 17% smoked, 21% had diabetes, 22% were female and &amp;gt;85% used any type of cardiovascular medication. During a median follow-up of 12.4 years [8.5–13.8], 1,010 deaths occurred due to CVD. A J-shaped continuous association was observed between BMI and CVD mortality with inverse associations for a BMI between 25–30 kg/m2, compared to 25 kg/m2. The nadir (HR, 95% CI) was 27.4 kg/m2 (HR: 0.94, 95% CI: 0.88, 1.00) (A). For WC, a non-linear association was observed with CVD mortality with higher mortality risks for a WC above 100 cm (A). Results were similar in patients with low versus high diet quality and in patients with low versus high physical activity (B), interaction terms were not significant (all p&amp;gt;0.55). Conclusion In MI patients, a BMI between 25–30 kg/m2 was associated with the lowest risk of CVD mortality. A WC above 100 cm was associated with a higher CVD mortality risk. The observed associations manifested independently of diet quality and physical activity level. Therefore, body adiposity seems to determine CVD mortality risk independently of underlying lifestyle factors. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Regio Deal Foodvalley

Dietary magnesium and risk of cardiovascular and all-cause mortality after myocardial infarction: A prospective analysis in the Alpha Omega Cohort.

BackgroundAn adequate intake of magnesium has been associated with lower risks of cardiovascular disease (CVD) and all-cause mortality in population-based studies. Whether an adequate magnesium intake is important for reducing long-term mortality risk after myocardial infarction (MI) is not yet clear.ObjectiveWe examined magnesium intake in relation to CVD, all-cause and coronary heart disease (CHD) mortality, on top of drug treatment, in patients who had experienced an MI.MethodsWe included 4,365 Dutch patients aged 60–80 y from the Alpha Omega Cohort with a history of MI <10 y before study enrollment. Dietary data over the past month were collected at baseline using a 203-item validated food frequency questionnaire from which magnesium intake was calculated. Patients were followed for cause-specific mortality through December 2018. HRs for mortality in tertiles of energy adjusted magnesium intake were obtained from multivariable Cox proportional hazard models, adjusting for age, sex, education, obesity and other lifestyle and dietary factors. Associations were also studied in relevant subgroups, including patients with diabetes and diuretics users. Restricted cubic splines were used for studying the continuous association of magnesium intake with CVD mortality.ResultsThe average magnesium intake was 302 ± 78 mg/day and 28% of male and 33% of female patients had adequate intakes. Magnesium containing supplements were used by 5.4% of the cohort. During a median follow-up of 12.4 years (48,473 person-years), 2,035 patients died, of which 903 from CVD and 558 from CHD. Higher magnesium intakes (>320 g/d), compared to the reference group (<283 mg/d), were associated with a lower risk of CVD mortality (HR: 0.72; 95% CI: 0.54–0.98) and all-cause mortality (HR: 0.78; 95% CI: 0.64–0.95) in the fully adjusted model. A non-significant inverse association was found for CHD mortality. Associations for CVD mortality were slightly stronger in diuretic users (HR: 0.55; 95% CI: 0.34–0.89). Results were similar after excluding magnesium supplement users.ConclusionAn adequate intake of magnesium may be important for lowering long-term mortality risk after MI, especially in patients treated with diuretics. The Alpha Omega Trial was registered at clinicaltrials.gov as NCT03192410.

Association of Sugar-Sweetened Beverages, Low/No-Calorie Beverages and Fruit Juice Intakes with Non-alcoholic Fatty Liver Disease: The SWEET Project

ObjectivesExamine associations between the intake of sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB), and fruit juice (FJ) and non-alcoholic fatty liver (NAFLD) in 4 population-based studies included in the SWEET project.MethodsData of 42,024 participants from the Lifelines Cohort Study (LCS), NQPlus, PREDIMED-Plus and the Alpha Omega Cohort (AOC) were cross-sectionally analyzed. Dietary intake was assessed using food frequency questionnaires. NAFLD was assessed using the Fatty Liver Index (≥60). Restricted cubic spline analyses were used to visualize dose-response associations in LCS. Multivariate Cox proportional hazard regression analyses with robust variance were performed for the associations with NAFLD (prevalence ratio [PR]) in all cohorts and linear regression analyses were conducted for the associations with its markers (triglycerides, gamma-glutamyl transferase, aspartate aminotransferase and alanine aminotransferase). Models were adjusted for demographic, lifestyle, and dietary factors. Results of different cohorts were pooled using random-effects meta-analysis.ResultsNAFLD prevalence was 22% in LCS and NQplus, 60% in AOC and 78% in PREDIMED-Plus. Each additional serving/day of SSB was associated with a 7% higher NAFLD prevalence (PR 1.07, 95%CI 1.03–1.10). For LNCB, dose-response analyses showed evidence for a nonlinear association with NAFLD i.e., a sharp increase at intake ≤ 1 serving/day and more gradual at higher intake levels. The intake of >2 LNCB servings/week was positively associated with NAFLD (PR 1.38, 95%CI 1.15–1.60, ref: non-consumers), which disappeared after adjustment for BMI (PR 1.04, 95%CI 0.94–1.14). A J-shaped association was observed between FJ and NAFLD with an inverse association for intakes of >0–2 servings/week (PR 0.92, 95%CI: 0.88–0.96), but not for higher intakes, compared to no intake. Modest positive associations were observed between all beverages and most NAFLD clinical markers.ConclusionsPooling results across 4 studies showed that SSB and LNCB were associated with higher NAFLD prevalence and the majority of its markers. A J-shaped association was observed between FJ and NAFLD, suggesting lower prevalence at medium intakes.Funding SourcesThe SWEET project has received funding from the European Union's Horizon 2020 research and innovation program.

Alcohol intake and long-term mortality risk after myocardial infarction in the Alpha Omega Cohort

ABSTRACTBackgroundPopulation-based studies generally show J-shaped associations between alcohol intake and mortality from cardiovascular disease (CVD). Little is known about alcohol and long-term mortality risk after myocardial infarction (MI).ObjectivesWe examined alcohol intake in relation to all-cause, CVD, and ischemic heart disease (IHD) mortality in Dutch post-MI patients of the Alpha Omega Cohort.MethodsThe analysis comprised 4365 patients (60–80 years; 79% male) with an MI ≤ 10 years before study enrolment. We used a 203-item FFQ to assess alcohol (total ethanol) and dietary intakes over the past month. Patients were classified as nondrinkers (0 g/d; n = 956) or very light (>0 to 2 g/d; n = 385), light (M: >2 to 10 g/d; F: >2 to 5 g/d; n = 1125), moderate (M: >10 to 30 g/d; F: >5 to 15 g/d; n = 1207), or heavy drinkers (M: >30 g/d; F: >15 g/d; n = 692). HRs of mortality for alcohol intake were obtained from Cox models, adjusting for age, sex, education, smoking, BMI, physical activity, and dietary factors.ResultsAlcohol was consumed by 83% of males and 61% of females. During ∼12 years of follow-up, 2035 deaths occurred, of which 903 were from CVD and 558 were from IHD. Compared to the (combined) reference group of nondrinkers and very light drinkers, HRs for all-cause mortality were 0.87 (95% CI, 0.78–0.98), 0.85 (95% CI, 0.75–0.96), and 0.91 (95% CI, 0.79–1.04) for light, moderate, and heavy drinkers, respectively. For CVD mortality, corresponding HRs were 0.80 (95% CI, 0.67–0.96), 0.82 (95% CI, 0.69–0.98), and 0.87 (95% CI, 0.70–1.08) for light, moderate, and heavy drinkers, respectively. Findings for IHD mortality were similar. HRs did not materially change when nondrinkers or very light drinkers were taken as the reference, or after exclusion of former drinkers or patients with diabetes or poor/moderate self-rated health.ConclusionsLight and moderate alcohol intakes were inversely associated with mortality risk in stable post-MI patients. These observational findings should be cautiously interpreted in light of the total evidence on alcohol and health. The Alpha Omega Cohort is registered at clinicaltrials.gov as NCT03192410.