Body Weight in Adolescent Men in Sweden and Risk of an Early Acute Coronary Event: A Prospective Population-Based Study.

Background Coronary heart disease remains the dominant cause of death worldwide. To improve cardiovascular disease prevention, knowledge of early key risk factors, especially those that are modifiable, is essential. The ongoing global obesity epidemic is of particular concern. We aimed to determine whether body mass index at conscription predicts early acute coronary events among men in Sweden. Methods and Results This was a population-based Swedish cohort study of conscripts (n=1 668 921; mean age, 18.3 years; 1968-2005), with follow-up through linkage to the nationwide Swedish patient and death registries. Risk of a first acute coronary event (hospitalization for acute myocardial infarction or coronary death) during follow-up (1-48 years) was calculated with generalized additive models. Objective baseline measures of fitness and cognition were included in the models in secondary analyses. During follow-up, there were 51 779 acute coronary events, of which 6457 (12.5%) were fatal within 30 days. Compared with men at the lowest end of the normal body mass index spectrum (body mass index, 18.5 kg/m2), an increasing risk for a first acute coronary event was observed, with hazard ratios (HRs) peaking at 40 years of age. After multivariable adjustments, men with a body mass index of 35 kg/m2 had an HR of 4.84 (95% CI, 4.29-5.46) for an event before the age of 40 years. Conclusions An increased risk of an early acute coronary event was detectable within normal levels of body weight at the age of 18 years, increasing to almost 5-fold in the highest weight category at 40 years of age. Given increasing levels of body weight and prevalence of overweight and obesity in young adults, the current decrease in coronary heart disease incidence in Sweden may flatten or even reverse in the near future.

Body Mass Index in Adolescence and Long-Term Risk of Early Incident Atrial Fibrillation and Subsequent Mortality, Heart Failure, and Ischemic Stroke.

Background We sought to determine the role of obesity in adolescent men on development of atrial fibrillation (AF) and subsequent associated clinical outcomes in subjects diagnosed with AF. Methods and Results We conducted a nationwide, register-based, cohort study of 1 704 467 men (mean age, 18.3±0.75 years) enrolled in compulsory military service in Sweden from 1969 through 2005. Height and weight, blood pressure, fitness, muscle strength, intelligence quotient, and medical disorders were recorded at baseline. Records obtained from the National Inpatient Registry and the Cause of Death Register were used to determine incidence and clinical outcomes of AF. During a median follow-up of 32 years (interquartile range, 24-41 years), 36 693 cases (mean age at diagnosis, 52.4±10.6 years) of AF were recorded. The multivariable-adjusted hazard ratio (HR) for AF increased from 1.06 (95% CI, 1.03-1.10) in individuals with body mass index (BMI) of 20.0 to <22.5 kg/m2 to 3.72 (95% CI, 2.44-5.66) among men with BMI of 40.0 to 50.0 kg/m2, compared with those with BMI of 18.5 to <20.0 kg/m2. During a median follow-up of ≈6 years in patients diagnosed with AF, we identified 3767 deaths, 3251 cases of incident heart failure, and 921 cases of ischemic stroke. The multivariable-adjusted HRs for all-cause mortality, incident heart failure, and ischemic stroke in AF-diagnosed men with baseline BMI >30 kg/m2 compared with those with BMI <20 kg/m2 were 2.86 (95% CI, 2.30-3.56), 3.42 (95% CI, 2.50-4.68), and 2.34 (95% CI, 1.52-3.61), respectively. Conclusions Increasing BMI in adolescent men is strongly associated with early AF, and with subsequent worse clinical outcomes in those diagnosed with AF with respect to all-cause mortality, incident heart failure, and ischemic stroke.

Effects of a Lacto-Ovo-Vegetarian Diet on the Plasma Lipidome and Its Association with Atherosclerotic Burden in Patients with Coronary Artery Disease-A Randomized, Open-Label, Cross-over Study.

A vegetarian diet has been associated with a lower risk of coronary artery disease (CAD). Plasma triacylglycerols, ceramides, and phosphatidylcholines may improve prediction of recurrent coronary events. We sought to investigate effects of a lacto-ovo-vegetarian diet (VD) on plasma lipidome in CAD patients and simultaneously assess associations of plasma lipids with the extent of coronary atherosclerotic burden. We analyzed 214 plasma lipids within glycerolipid, sphingolipid, and sterol lipid classes using lipidomics from a randomized controlled, crossover trial comprising 31 CAD patients on standard medical therapy. Subjects completed a four-week intervention with VD and isocaloric meat diet (MD), separated by a four-week washout period. The VD increased levels of 11 triacylglycerols and lowered 7 triacylglycerols, 21 glycerophospholipids, cholesteryl ester (18:0), and ceramide (d18:1/16:0) compared with MD. VD increased triacylglycerols with long-chain polyunsaturated fatty acyls while decreased triacylglycerols with saturated fatty acyls, phosphatidylcholines, and sphingomyelins than MD. The Sullivan extent score (SES) exhibited on coronary angiograms were inversely associated with triacylglycerols with long-chain unsaturated fatty acyls. Phosphatidylcholines that were lower with VD were positively associated with SES and the total number of stenotic lesions. The VD favorably changed levels of several lipotoxic lipids that have previously been associated with increased risk of coronary events in CAD patients.

Effects of a Vegetarian Diet on Cardiometabolic Risk Factors, Gut Microbiota, and Plasma Metabolome in Subjects With Ischemic Heart Disease: A Randomized, Crossover Study.

Background A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease. Methods and Results A randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4-week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4-week washout period. The primary outcome was difference in oxidized low-density lipoprotein cholesterol (LDL-C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short-chain and branched-chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL-C (-2.73 U/L), total cholesterol (-5.03 mg/dL), LDL-C (-3.87 mg/dL), and body weight (-0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, including l-carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL-C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae. Conclusions The VD in conjunction with optimal medical therapy reduced levels of oxidized LDL-C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL-C observed with the VD. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02942628.

Social Support and Subclinical Coronary Artery Disease in Middle-Aged Men and Women: Findings from the Pilot of Swedish CArdioPulmonary bioImage Study.

Social support has been associated with coronary artery disease (CAD), particularly in individuals who have sustained a cardiovascular event. This study investigated the relationship between social support and subclinical CAD among 1067 healthy middle-aged men and women. Social support was assessed with validated social integration and emotional attachment measures. Subclinical CAD was assessed as a coronary artery calcium score (CACS) using computed tomography. There was no association between social support and CACS in men. In women, low social support was strongly linked to cardiovascular risk factors, high levels of inflammatory markers, and CACS > 0. In a logistic regression model, after adjustment for 12 cardiovascular risk factors, the odds ratio (95% confidence intervals) for CACS > 0 in women with the lowest social integration, emotional attachment, and social support groups (reference: highest corresponding group) were 2.47 (1.23-5.12), 1.87 (0.93-3.59), and 4.28 (1.52-12.28), respectively. Using a machine learning approach (random forest), social integration was the fourth (out of 12) most important risk factor for CACS > 0 in women. Women with lower compared to higher or moderate social integration levels were about 14 years older in "vascular age". This study showed an association between lack of social support and subclinical CAD in middle-aged women, but not in men. Lack of social support may affect the atherosclerotic process and identify individuals vulnerable to CAD events.

Serum untargeted lipidomic profiling reveals dysfunction of phospholipid metabolism in subclinical coronary artery disease.

Purpose: Disturbed metabolism of cholesterol and triacylglycerols (TGs) carries increased risk for coronary artery calcification (CAC). However, the exact relationship between individual lipid species and CAC remains unclear. The aim of this study was to identify disturbances in lipid profiles involved in the calcification process, in an attempt to propose potential biomarker candidates. Patients and methods: We studied 70 patients at intermediate risk for coronary artery disease who had undergone coronary calcification assessment using computed tomography and Agatston coronary artery calcium score (CACS). Patients were divided into three groups: with no coronary calcification (NCC; CACS: 0; n=26), mild coronary calcification (MCC; CACS: 1-250; n=27), or severe coronary calcification (SCC; CACS: >250; n=17). Patients' serum samples were analyzed using liquid chromatography-mass spectrometry in an untargeted lipidomics approach. Results: We identified 103 lipids within the glycerolipid, glycerophospholipid, sphingolipid, and sterol lipid classes. After false discovery rate correction, phosphatidylcholine (PC)(16:0/20:4) in higher levels and PC(18:2/18:2), PC(36:3), and phosphatidylethanolamine(20:0/18:2) in lower levels were identified as correlates with SCC compared to NCC. There were no significant differences in the levels of individual TGs between the three groups; however, clustering the lipid profiles showed a trend for higher levels of saturated and monounsaturated TGs in SCC compared to NCC. There was also a trend for lower TG(49:2), TG(51:1), TG(54:5), and TG(56:8) levels in SCC compared to MCC. Conclusion: In this study we investigated the lipidome of patients with coronary calcification. Our results suggest that the calcification process may be associated with dysfunction in autophagy. The lipidomic biomarkers revealed in this study may aid in better assessment of patients with subclinical coronary artery disease.

Impact of socioeconomic status on coronary artery calcification.

Background Low socioeconomic status is associated with an increased risk of coronary artery disease, but few studies have investigated the potential link between living in an area with a low versus a high socioeconomic status and coronary artery calcification, a marker of subclinical coronary artery disease. Design The design of this study was a cross-sectional study. Methods We evaluated 1067 participants with no history of coronary artery disease from the pilot phase of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Men and women aged 50-64 years were recruited from three high-socioeconomic status ( n = 541) and three low-socioeconomic status ( n = 526) areas in the city of Gothenburg (550,000 inhabitants). The coronary artery calcification score was assessed with the Agatston method using computed tomography, with individuals classified into either no coronary calcification ( n = 625; mean age, 57 years) or any coronary artery calcification ( n = 442; mean age, 59 years (men, 68.5%)). Results Coronary artery calcification was present in 244 (46.3%) and 198 (36.6%) individuals from the low- and high-socioeconomic status areas, respectively. Participants from the low-socioeconomic status areas had a significantly higher risk factor burden. In a multivariable logistic regression model with adjustment for age, sex and cardiovascular risk factors, the odds for coronary artery calcification were not significantly higher among persons living in low-socioeconomic status areas (odds ratio = 1.18, 95% confidence interval = 0.87-1.60). Conclusion In this relatively small cross-sectional study, we observed an association between living in a low-socioeconomic status area and coronary artery calcification. However, this was mostly explained by higher levels of cardiovascular disease risk factors, indicating that the effect of socioeconomic status on the atherosclerotic process works through an increased burden of cardiovascular disease risk factors.

Replication of LC-MS untargeted lipidomics results in patients with calcific coronary disease: An interlaboratory reproducibility study.

BACKGROUND: Recently a lipidomics approach was able to identify perturbed fatty acyl chain (FAC) and sphingolipid moieties that could stratify patients according to the severity of coronary calcification, a form of subclinical atherosclerosis. Nevertheless, these findings have not yet been reproduced before generalising their application. The aim of this study was to evaluate the reproducibility of lipidomics approaches by replicating previous lipidomic findings in groups of patients with calcific coronary artery disease (CCAD). METHODS: Patients were separated into the following groups based on their calcium score (CS); no calcification (CS: 0; n=26), mild calcification (CS: 1-250; n=27) and severe calcification (CS: >250; n=17). Two serum samples were collected from each patient and used for comparative analyses by 2 different laboratories, in different countries and time points using liquid chromatography coupled to mass spectrometry untargeted lipidomics methods. RESULTS: Six identical metabolites differentiated patients with severe coronary artery calcification from those with no calcification were found by both laboratories independently. Additionally, relative intensities from the two analyses demonstrated high correlation coefficients. Phosphatidylcholine moieties with 18-carbon FAC were identified in lower intensities and 20:4 FAC in higher intensities in the serum of diseased group. Moreover, 3 common sphingomyelins were detected. CONCLUSION: This is the first interlaboratory reproducibility study utilising lipidomics applications in general and specifically in patients with CCAD. Lipid profiling applications in patients with CCAD are very reproducible in highly specialised and experienced laboratories and could be applied in clinical practice in order to spare patients diagnostic radiation.

Persistent reduced myocardial deformation in neonates after CoA repair.

INTRODUCTION: Surgical repair of coarctation of the aorta (CoA) is a safe procedure in children, however the condition is known for its potential recurrence and other related complications. The available evidence shows abnormal intrinsic properties of the aorta in CoA, thus suggesting additional effect, even after CoA repair, on left ventricular (LV) function. Accordingly, we sought to obtain a better understanding of LV myocardial mechanics in very early-corrected CoA using two-dimensional STE. METHODS AND RESULTS: We retrospectively studied 21 patients with corrected CoA at a median age of 9 (2-53) days at three time points: 1) just before intervention, 2) at short-term follow-up and 3) at medium-term follow-up after intervention and compared them with normal values. Speckle tracking analysis was conducted via vendor independent software, Tomtec. After intervention, LV function significantly improved (from -12.8±3.9 to -16.7±1.7; p<0.001), however normal values were not reached even at medium term follow-up (-18.3±1.7 vs. -20±1.6; p=0.002). Medium term longitudinal strain correlated with pre intervention EF (r=0.58, p=0.006). Moreover, medium term subnormal values were more frequently associated with bicuspid aortic valve (33.3% vs. 66.6%; p<0.05). CONCLUSION: LV myocardial function in neonates with CoA can be feasibly evaluated and followed up by speckle tracking echocardiography. LV subendocardial dysfunction however, remains in early infancy coarctation long after repair. Long-term follow-up through adulthood using myocardial deformation measurements should shed light on the natural history and consequences of this anomaly.