Diets with Higher Insulinemic Potential Are Associated with Increased Risk of Overall and Cardiovascular Disease-specific Mortality

Abstract Hyperinsulinemia and insulin resistance have been proposed to be associated with mortality risk, and diet can modulate insulin response. However, whether dietary patterns with high insulinemic potential are associated with mortality remains unknown. We prospectively examined the associations between hyperinsulinemic diets and the risk of total and cause-specific mortality in a large nationally representative population. Dietary factors were assessed by 24-hour recalls. Two empirical dietary indices for hyperinsulinemia (EDIH) and insulin resistance (EDIR) were developed to identify food groups most predictive of biomarkers for hyperinsulinemia (C-peptide and insulin) and insulin resistance (homeostatic model assessment for insulin resistance), respectively. Deaths from date of the first dietary interview until December 31, 2015 were identified by the National Death Index. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models. During a median follow-up of 7.8 years, 4,904 deaths were documented among 40,074 participants. For EDIH, the multivariable-adjusted HRs (comparing extreme quintiles) were 1.20 (95% CI: 1.09-1.32, P-trend<0.001) for overall mortality, and 1.41 (95% CI: 1.15-1.74, P-trend=0.002) for cardiovascular disease (CVD) mortality. Similar associations were observed for EDIR with HRs of 1.18 (95% CI: 1.07-1.29, P-trend<0.001) for total and 1.35 (95% CI: 1.09-1.67, P-trend=0.005) for CVD mortality. After further adjustments for body mass index and diabetes, these positive associations were somewhat attenuated, but most remained statistically significant. Our findings suggested that diets with higher insulinemic potential are associated with increased risk of overall and CVD-specific mortality. Strategies to avoid hyperinsulinemic dietary patterns may potentially promote health and longevity.

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Genetic and Metabolite Variability in One-Carbon Metabolism Applied to an Insulin Resistance Model in Patients With Schizophrenia Receiving Atypical Antipsychotics

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.623143 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kristen M. Ward ◽

Kyle Burghardt ◽

A. Zarina Kraal ◽

Andrew Jaeger ◽

Larisa Yeomans ◽

...

Keyword(s):

Insulin Resistance ◽

Cardiovascular Disease ◽

Carbon Metabolism ◽

Carrier Status ◽

Diabetes Diagnosis ◽

Model Assessment ◽

Least Squares Regression ◽

Increased Risk ◽

Homeostatic Model Assessment ◽

One Carbon Metabolism

Background: Patients with schizophrenia are at high risk of pre-mature mortality due to cardiovascular disease (CVD). Our group has completed studies in pharmacogenomics and metabolomics that have independently identified perturbations in one-carbon metabolism as associated with risk factors for CVD in this patient population. Therefore, this study aimed to use genetic and metabolomic data to determine the relationship between folate pharmacogenomics, one-carbon metabolites, and insulin resistance as measured using the homeostatic model assessment for insulin resistance (HOMA-IR) as a marker of CVD.Methods: Participants in this pilot analysis were on a stable atypical antipsychotic regimen for at least 6 months, with no diabetes diagnosis or use of antidiabetic medications. Participant samples were genotyped for MTHFR variants rs1801131 (MTHFR A1298C) and rs1801133 (MTHFR C677T). Serum metabolite concentrations were obtained with NMR. A least squares regression model was used to predict log(HOMA-IR) values based on the following independent variables: serum glutamate, glycine, betaine, serine, and threonine concentrations, and carrier status of the variant alleles for the selected genotypes.Results: A total of 67 participants were included, with a median age of 47 years old (IQR 42–52), 39% were female, and the median BMI was 30.3 (IQR 26.3–37.1). Overall, the model demonstrated an ability to predict log(HOMA-IR) values with an adjusted R2 of 0.44 and a p-value of < 0.001. Glutamate, threonine, and carrier status of the MTHFR 1298 C or MTHFR 677 T allele were positively correlated with log(HOMA-IR), whereas glycine, serine, and betaine concentrations trended inversely with log(HOMA-IR). All factors included in this final model were considered as having a possible effect on predicting log(HOMA-IR) as measured with a p-value < 0.1.Conclusions: Presence of pharmacogenomic variants that decrease the functional capacity of the MTHFR enzyme are associated with increased risk for cardiovascular disease, as measured in this instance by log(HOMA-IR). Furthermore, serine, glycine, and betaine concentrations trended inversely with HOMA-IR, suggesting that increased presence of methyl-donating groups is associated with lower measures of insulin resistance. Ultimately, these results will need to be replicated in a significantly larger population.

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Abstract 14043: Association of Non-Alcoholic Steatohepatitis Assessed by Fib-4 Index and Risk of Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.142.suppl_3.14043 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Aliza Hussain ◽

VIJAY NAMBI ◽

Elizabeth Selvin ◽

Wensheng Sun ◽

Kunihiro Matsushita ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Cox Regression ◽

Advanced Fibrosis ◽

Cvd Risk ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study ◽

Cvd Mortality

Introduction: Cardiovascular disease (CVD) is the most common cause of death in nonalcoholic steatohepatitis (NASH). While these conditions share many cardio-metabolic risk factors including metabolic syndrome, diabetes and dyslipidemia, limited data exist on whether NASH is independently and prospectively associated with incident CVD beyond traditional risk factors. Fibrosis-4 (FIB-4) index is a scoring system based on platelet count, age, AST and ALT, shown to be comparable to magnetic resolution elastography for predicting advanced fibrosis in biopsy-proven NASH. We sought to evaluate the association of elevated FIB-4 with global CVD events and CVD mortality in the Atherosclerosis Risk in Communities (ARIC) Study Methods: We studied 5531 individuals, mean age of 76 (SD 5.2) years, 58% female, 22% black, at ARIC visit 5 (2011-2013). FIB-4 was categorized as low risk of advanced fibrosis for score <1.45, intermediate for 1.45-3.25 and high for >3.25. Cox regression was used to estimate the association of FIB-4 with time to first global CVD event (CHD, ischemic stroke or heart failure hospitalization) and CVD mortality adjusted for pooled cohort equation risk factors. Results: Over a median follow up of 6.2 (5.3-6.8) years, there were 1108 global CVD events and 457 CVD deaths. In adjusted models, compared to participants with low FIB-4 (<1.45), those with elevated FIB-4 >3.25, had significantly increased risk for global CVD events (HR 1.58, 95% CI 1.23-2.02) and CVD mortality (HR 1.70, 95% CI 1.16-2.50). Conclusions: In a large prospective cohort, presence of advanced liver fibrosis, as assessed by elevated FIB-4 index >3.25, was associated with increased risk for CVD events and CVD mortality, beyond traditional CVD risk factors. Future clinical trials of candidate medications under study for NASH should examine whether effective NASH treatment will impact CV outcomes.

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Frequency of Boiled Potato Consumption and All-Cause and Cardiovascular Disease Mortality in the Prospective Population-Based HUNT Study

Frontiers in Nutrition ◽

10.3389/fnut.2021.681365 ◽

2021 ◽

Vol 8 ◽

Author(s):

Trine Moholdt ◽

Tom I. L. Nilsen

Keyword(s):

Cardiovascular Disease ◽

Cox Regression ◽

Population Based ◽

Disease Mortality ◽

Norwegian Population ◽

Increased Risk ◽

All Cause Mortality ◽

Hunt Study ◽

Potato Consumption ◽

Cvd Mortality

Few studies have assessed the association between potato consumption and mortality, especially cardiovascular disease (CVD) mortality. Our objective was to investigate the association between consumption of boiled potatoes and all-cause and CVD mortality in a Norwegian population. We used data from the population based HUNT3 study in Norway, with data on boiled potato consumption frequency in 2006–2008 from 49,926 males and females aged 20 years or above. All-cause and CVD mortality were identified during 10 years follow-up through the national Cause of Death Registry, which is virtually complete. We used Cox regression to estimate hazard ratio (HR) with a 95% confidence interval (CI) for death controlling for potential confounders, and conducted additional analyses stratified by sex, body mass index (BMI) ±25 kg/m2, and age ±65 years. There were 4,084 deaths and 1,284 of these were due to CVD. Frequency of boiled potato consumption was not associated with all-cause mortality, nor with CVD mortality. Compared to those individuals who consumed boiled potatoes less than once weekly, those who reported to consume boiled potatoes 1–3 times per week had an adjusted HR (95% CI) of 1.12 (0.89, 1.41) for all-cause mortality and 1.20 (0.78, 1.86) for CVD mortality. Individuals who consumed boiled potatoes 4–6 times per week had HRs of 0.97 (0.78, 1.21) and 1.03 (0.68, 1.55), for all-cause and CVD mortality, respectively, whereas those who consumed boiled potatoes more than once daily had HRs of 1.04 (0.83, 1.29) and 1.09 (0.73, 1.63) for all-cause and CVD mortality, respectively. There was no evidence of differential associations for males vs. females, nor between people with BMI ± 25 kg/m2. The associations between frequency of boiled potato consumption and all-cause mortality showed different patterns between those younger vs. older than 65 years, with a tendency of increased risk only in the oldest age group. In conclusion, frequency of consumption of boiled potatoes was not associated with all-cause or CVD mortality in the HUNT population in Norway.

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Association between Aminotransferase/alanine Aminotransferase Ratio and Cardiovascular Disease mortality in Patients on Peritoneal Dialysis: A Multi-center Retrospective Study

10.21203/rs.2.21568/v2 ◽

2020 ◽

Author(s):

Xiaoran Feng ◽

Yueqiang Wen ◽

FenFen Peng ◽

Niansong Wang ◽

Xiaojiang Zhan ◽

...

Keyword(s):

Cardiovascular Disease ◽

Peritoneal Dialysis ◽

Alanine Aminotransferase ◽

Cox Regression ◽

Significant Risk ◽

Kaplan Meier ◽

Disease Mortality ◽

Increased Risk ◽

Cvd Mortality

Abstract Objectives: Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention.Methods: A total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model.Results: Of eligible 1579 patients with a mean age of 49.3±14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P=0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR)=1.50, 95% confidence index (CI) 1.09-2.07, P=0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR=1.43, 95%CI 1.08-2.41, P=0.002). Conclusions: PD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.

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Incident Gout: Risk of Death and Cause-specific Mortality in Western Sweden – a Nested Case Control Study

10.21203/rs.3.rs-586033/v1 ◽

2021 ◽

Author(s):

Mats Dehlin ◽

Tatiana Zverkova Sandström ◽

Lennart TH Jacobsson

Keyword(s):

Cardiovascular Disease ◽

Cause Of Death ◽

Cox Regression ◽

Temporal Trends ◽

Healthcare Database ◽

Risk Of Death ◽

Increased Risk ◽

Specific Mortality ◽

Time Periods ◽

Incident Cases

Abstract BackgroundExcess mortality in gout has mainly been attributed to cardiovascular disease (CVD). In the light of decreased CVD-mortality in general we wanted to evaluate the risk of overall mortality in gout and cause-specific contributions to mortality beyond CVD as well as temporal trends of it.MethodsAll incident cases of gout between 2006-2015 in western Sweden were identified in the healthcare database VEGA. Up to 5 population controls per case matched on age, sex and county were identified. Relevant comorbidities were identified for 5 years preceding index date in VEGA. Follow-up until the first of death, migration or study end 31 of December 2017. Cause of death was identified and cause-specific mortality grouped as: cardiovascular disease (CVD), renal disease (RD), dementia (DEM), infections, diabetes, diseases of the digestive system (DDS), lung diseases, cancer (CA) and other. Effect of gout on risk of death was calculated using COX regression on whole population and stratified by sex, adjusted for demographics and comorbidities. Death incidence rate were compared between the two time periods, 2006-2010 and 2011-2015.ResultsWe identified 22055 cases of incident gout and 98 946 controls, mean age (SD) 67.3-66.3 (15.3-15.4) years and 67.6-66.5% males. All comorbidities were more common at baseline among gout cases except for dementia which was more common in controls. Overall risk for death in incident gout was increased with 3%. Gout cases had a significantly increased risk for death by CVD, RD and DDS and a significantly decreased risk for death by DEM and CA. Similar results were found when stratifying for sex. There were no significant differences in incident death rate ratios in total, and subdivided into CVD and non CVD cause of death, between cases and controls in the two time periods examined.ConclusionsA 3% increase in all-cause death in patients with gout highlights the importance in addressing not only CVD risk factors in the management of gout patients. Furthermore, gout was associated with reduced mortality from dementia and these findings calls for further study, not least because of possible effects of urate lowering therapy on risk of dementia.

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Association between Aminotransferase/alanine Aminotransferase Ratio and Cardiovascular Disease mortality in Patients on Peritoneal Dialysis

10.21203/rs.2.21568/v3 ◽

2020 ◽

Author(s):

Xiaoran Feng ◽

Yueqiang Wen ◽

FenFen Peng ◽

Niansong Wang ◽

Xiaojiang Zhan ◽

...

Keyword(s):

Cardiovascular Disease ◽

Peritoneal Dialysis ◽

Alanine Aminotransferase ◽

Cox Regression ◽

Significant Risk ◽

Kaplan Meier ◽

Disease Mortality ◽

Increased Risk ◽

Cvd Mortality

Abstract Background Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention. Methods A total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model. Results Of eligible 1579 patients with a mean age of 49.3±14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P=0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR)=1.50, 95% confidence index (CI) 1.09-2.07, P=0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR=1.43, 95%CI 1.08-2.41, P=0.002). Conclusions PD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.

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Association between Aminotransferase/alanine Aminotransferase Ratio and Cardiovascular Disease mortality in Patients on Peritoneal Dialysis

10.21203/rs.2.21568/v4 ◽

2020 ◽

Author(s):

Xiaoran Feng ◽

Yueqiang Wen ◽

FenFen Peng ◽

Niansong Wang ◽

Xiaojiang Zhan ◽

...

Keyword(s):

Cardiovascular Disease ◽

Peritoneal Dialysis ◽

Alanine Aminotransferase ◽

Cox Regression ◽

Significant Risk ◽

Kaplan Meier ◽

Disease Mortality ◽

Increased Risk ◽

Cvd Mortality

Abstract Background: Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention.Methods: A total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model.Results: Of eligible 1579 patients with a mean age of 49.3±14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P=0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR)=1.50, 95% confidence index (CI) 1.09-2.07, P=0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR=1.43, 95%CI 1.08-2.41, P=0.002). Conclusions: PD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.

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Association between Aminotransferase/alanine Aminotransferase Ratio and Cardiovascular Disease mortality in Patients on Peritoneal Dialysis

10.21203/rs.2.21568/v1 ◽

2020 ◽

Author(s):

Xiaoran Feng ◽

Yueqiang Wen ◽

FenFen Peng ◽

Niansong Wang ◽

Xiaojiang Zhan ◽

...

Keyword(s):

Cardiovascular Disease ◽

Peritoneal Dialysis ◽

Alanine Aminotransferase ◽

Cox Regression ◽

Significant Risk ◽

Kaplan Meier ◽

Disease Mortality ◽

Increased Risk ◽

Cvd Mortality

Abstract Objectives Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention.Methods A total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model.Results Of eligible 1579 patients with a mean age of 49.3±14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P=0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR)=1.50, 95% confidence index (CI) 1.09-2.07, P=0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR=1.43, 95%CI 1.08-2.41, P=0.002).Conclusions PD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.

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Dose–Response Relation between Tea Consumption and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis of Population-Based Studies

Advances in Nutrition ◽

10.1093/advances/nmaa010 ◽

2020 ◽

Vol 11 (4) ◽

pp. 790-814 ◽

Cited By ~ 4

Author(s):

Mei Chung ◽

Naisi Zhao ◽

Deena Wang ◽

Marissa Shams-White ◽

Micaela Karlsen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cohort Studies ◽

Prospective Cohort ◽

Lower Risk ◽

Meta Analysis ◽

Risk Of Bias ◽

Tea Consumption ◽

All Cause Mortality ◽

Specific Mortality ◽

Cvd Mortality

ABSTRACT Tea flavonoids have been suggested to offer potential benefits to cardiovascular health. This review synthesized the evidence on the relation between tea consumption and risks of cardiovascular disease (CVD) and all-cause mortality among generally healthy adults. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Food Science and Technology Abstracts, and Ovid CAB Abstract databases were searched to identify English-language publications through 1 November 2019, including randomized trials, prospective cohort studies, and nested case-control (or case-cohort) studies with data on tea consumption and risk of incident cardiovascular events (cardiac or peripheral vascular events), stroke events (including mortality), CVD-specific mortality, or all-cause mortality. Data from 39 prospective cohort publications were synthesized. Linear meta-regression showed that each cup (236.6 mL) increase in daily tea consumption (estimated 280 mg and 338 mg total flavonoids/d for black and green tea, respectively) was associated with an average 4% lower risk of CVD mortality, a 2% lower risk of CVD events, a 4% lower risk of stroke, and a 1.5% lower risk of all-cause mortality. Subgroup meta-analysis results showed that the magnitude of association was larger in elderly individuals for both CVD mortality (n = 4; pooled adjusted RR: 0.89; 95% CI: 0.83, 0.96; P = 0.001), with large heterogeneity (I2 = 72.4%), and all-cause mortality (n = 3; pooled adjusted RR: 0.92; 95% CI: 0.90, 0.94; P < 0.0001; I2 = 0.3%). Generally, studies with higher risk of bias appeared to show larger magnitudes of associations than studies with lower risk of bias. Strength of evidence was rated as low and moderate (depending on study population age group) for CVD-specific mortality outcome and was rated as low for CVD events, stroke, and all-cause mortality outcomes. Daily tea intake as part of a healthy habitual dietary pattern may be associated with lower risks of CVD and all-cause mortality among adults.

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Associations between dietary patterns and the incidence of total and fatal cardiovascular disease and all-cause mortality in 116,806 individuals from the UK Biobank: a prospective cohort study

BMC Medicine ◽

10.1186/s12916-021-01958-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Min Gao ◽

Susan A. Jebb ◽

Paul Aveyard ◽

Gina L. Ambrosini ◽

Aurora Perez-Cornago ◽

...

Keyword(s):

Cardiovascular Disease ◽

Energy Density ◽

Dietary Patterns ◽

Dietary Pattern ◽

Saturated Fat ◽

Dietary Advice ◽

Free Sugars ◽

Linear Association ◽

Increased Risk ◽

All Cause Mortality

Abstract Background Traditionally, studies investigating diet and health associations have focused on single nutrients. However, key nutrients co-exist in many common foods, and studies focusing solely on individual nutrients may obscure their combined effects on cardiovascular disease (CVD) and all-cause mortality. We aimed to identify food-based dietary patterns which operate through excess energy intake and explain high variability in energy density, free sugars, saturated fat, and fiber intakes and to investigate their association with total and fatal CVD and all-cause mortality. Methods Detailed dietary data was collected using a 24-h online dietary assessment on two or more occasions (n = 116,806). We used reduced rank regression to derive dietary patterns explaining the maximum variance. Multivariable Cox-proportional hazards models were used to investigate prospective associations with all-cause mortality and fatal and non-fatal CVD. Results Over an average of 4.9 years of follow-up, 4245 cases of total CVD, 838 cases of fatal CVD, and 3629 cases of all-cause mortality occurred. Two dietary patterns were retained that jointly explained 63% of variation in energy density, free sugars, saturated fat, and fiber intakes in total. The main dietary pattern was characterized by high intakes of chocolate and confectionery, butter and low-fiber bread, and low intakes of fresh fruit and vegetables. There was a positive linear association between the dietary pattern and total CVD [hazard ratio (HR) per z-score 1.07, 95% confidence interval (CI) 1.04–1.09; HRtotal CVD 1.40, 95% CI 1.31–1.50, and HRall-cause mortality 1.37, 95% CI 1.27–1.47 in highest quintile]. A second dietary pattern was characterized by a higher intakes of sugar-sweetened beverages, fruit juice, and table sugar/preserves. There was a non-linear association with total CVD risk and all-cause mortality, with increased risk in the highest quintile [HRtotal CVD 1.14, 95% CI 1.07–1.22; HRall-cause mortality 1.11, 95% CI 1.03–1.19]. Conclusions We identified dietary patterns which are associated with increased risk of CVD and all-cause mortality. These results help identify specific foods and beverages which are major contributors to unhealthy dietary patterns and provide evidence to underpin food-based dietary advice to reduce health risks.

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