Cardiovascular Risk Factors Associated With Blood Metabolite Concentrations and Their Alterations During a 4-Year Period in a Population-Based Cohort

Abstract

C ardiovascular disease (CVD) is a leading cause of mortality, accounting for >30% of deaths worldwide.1 There are several modifiable (ie, obesity, smoking, alcohol, physical activity, and diet) and also unmodifiable risk factors (ie, sex and age) associated with CVD; however, the pathophysiological mechanisms of the association between risk factors and disease are not yet fully understood. Clinical Perspective on p 494Metabolomics aims to quantify small molecules present in a biological system at a specific time point. This snapshot provides an indication of the current metabolic state of the whole organism at a given stage of life. Differences in metabolic profiles can be because of pathological stimuli, environmental impact, or normal physiological variations. Several studies have shown that metabolomics can identify distinct metabolic patterns in individuals affected by pathological conditions, that is, atherosclerosis, diabetes mellitus, or cardiovascular disorders. 2-5The effects of several classic modifiable CVD risk factors on metabolism have already been studied in different population-based cohorts. In particular, alcohol intake, obesity, diet patterns, and smoking were shown to be associated Background-The effects of lifestyle risk factors considered collectively on the human metabolism are to date unknown.We aim to investigate the association of these risk factors with metabolites and their changes during 4 years. Methods and Results-One hundred and sixty-three metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45 to 83 years at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lysophosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (body mass index [BMI], alcohol consumption, smoking, diet, and exercise). Multilevel or simple linear regression modeling adjusted for relevant covariates was used for the evaluation of cross-sectional or longitudinal associations, respectively; multiple testing correction was based on false discovery rate. BMI, alcohol consumption, and smoking were associated with lipid metabolism (reduced lyso-and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines, and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines. with alterations in lipid metabolism. Additionally, obe...

Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC

“…The metabolic signature of lifetime alcohol intake was negatively associated with sphingomyelins and positively associated with phosphatidylcholines. In the CARLA study, in both men and women, PC aaC32:1 was positively associated with alcohol consumption while PC aeC30:2, SM(OH) C14:1, SM(OH) C16:1, and SM(OH) C22:2 were inversely associated with high intakes of alcohol (62). Similar metabolite patterns were observed in a study that focused on alcohol-dependent patients (63).…”

“…As a result, the estimated proportion of mediation increased from 57% to 100%, resulting in a metabolic signature capturing smokingrelated metabolic features that is more predictive of HCC. In the CARLA study, that has also explored lifestyle exposures' relation with serum metabolite levels, a sex-specific positive association was found between PC aaC32:1 and smoking in men and with SM C16:1 and BMI in women (62). Smoking disrupts PC levels, with low acyl-alkyl PCs and high diacyl PCs likely reflecting less lipid remodeling in membranes resulting in inflammation (74), which may in turn lead to liver injury (75).…”

Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort

“…To our knowledge, three previous population-based studies have investigated associations of total alcohol intake [ 9 , 10 ] and/or consumption of specific alcoholic beverages [ 11 ] with circulating concentrations of a panel of metabolites using a targeted metabolomics approach (BIOCRATES AbsoluteIDQTM p150 kit). These studies were conducted in German populations ( n = 2090 [ 9 ] and n = 1030 [ 10 ]), and in over 3500 female twins from the United Kingdom [ 11 ], and mainly observed associations of self-reported alcohol intake with phospholipid and sphingolipid metabolism. Two of these studies partly replicated their findings in similar cohorts [ 9 , 11 ].…”

“…Two of these studies partly replicated their findings in similar cohorts [ 9 , 11 ]. However, no study has yet investigated these associations in other European populations, and potential sex-specific associations remain unclear [ 9 , 10 ]. Furthermore, no study to date has examined how these associations may be influenced by smoking habits.…”

Pathways of Prevention: A Scoping Review of Dietary and Exercise Interventions for Neurocognition

“…also potentially consistent with the increased rates of ADRD among individuals with different apolipoprotein (APOE) genotypes, as the APOE gene was originally discovered because of its lipid metabolizing properties. It is therefore possible that blunted peripheral metabolic function may impair the brain's ability to offset normative neurodegeneration, with marked dysregulation of phospholipid metabolism occurring in the years immediately preceding clinical neurocognitive impairment [101][102][103][104][105].…”