Apolipoprotein E (apoE) is the key regulator of plasma lipids, mediating altered functionalities in lipoprotein metabolism - affecting the risk of coronary artery (CAD) and Alzheimer's diseases, as ...well as longevity. Searching pathways influenced by apoE prior to adverse manifestations, we utilized a metabolome dataset of 228 nuclear-magnetic-resonance-measured serum parameters with a 10-year follow-up from the population-based Young Finns Study cohort of 2,234 apoE-genotyped (rs7412, rs429358) adults, aged 24-39 at baseline. At the end of our follow-up, by limiting FDR-corrected p < 0.05, regression analyses revealed 180/228 apoE-polymorphism-related associations with the studied metabolites, in all subjects - without indications of apoE x sex interactions. Across all measured apoE- and apoB-containing lipoproteins, ε4 allele had consistently atherogenic and ε2 protective effect on particle concentrations of free/esterified cholesterol, triglycerides, phospholipids and total lipids. As novel findings, ε4 associated with glycoprotein acetyls, LDL-diameter and isoleucine - all reported biomarkers of CAD-risk, inflammation, diabetes and total mortality. ApoE-subgroup differences persisted through our 10-year follow-up, although some variation of individual metabolite levels was noticed. In conclusion, apoE polymorphism associate with a complex metabolic change, including aberrations in multiple novel biomarkers related to elevated cardiometabolic and all-cause mortality risk, extending our understanding about the role of apoE in health and disease.
The aim of the present study was to examine whether pulse wave velocity (PWV) predicts the progression of blood pressure and the development of hypertension in young adults. In addition, we studied ...whether PWV improves the risk prediction of incident hypertension beyond traditional cardiovascular risk factors. Systolic and diastolic blood pressures were measured in 2007 and 2011 for 1449 Finnish adults (aged 30–45 years). In addition, PWV and other cardiovascular risk factors were measured in 2007. The association between PWV (in 2007) and blood pressure (in 2011) was studied in the whole population (n=1449) and in a normotensive subpopulation (n=1183). The ability of PWV measured in 2007 to predict incident hypertension in 2011 was investigated in the subpopulation (n=1183). PWV measured in 2007 was directly and independently associated with systolic and diastolic blood pressures measured in 2011 (P<0.001 for both). PWV measured in 2007 was also an independent predictor of incident hypertension in 2011 (odds ratio, 1.96 per 1-SDincrease; 95% confidence interval, 1.51–2.57; P<0.001). The extended prediction model (including PWV) improved the incident hypertension risk prediction beyond traditional cardiovascular risk factors, the area under receiver operating characteristics curve being 0.833 versus 0.809 (P=0.040), and the continuous net reclassification improvement 59.4% (P<0.001). These findings suggest that PWV predicts the progression of blood pressure and could provide a valuable tool in hypertension risk prediction in young adults.
Branched-chain and aromatic amino acids are associated with the risk for future type 2 diabetes; however, the underlying mechanisms remain elusive. We tested whether amino acids predict insulin ...resistance index in healthy young adults.
Circulating isoleucine, leucine, valine, phenylalanine, tyrosine, and six additional amino acids were quantified in 1,680 individuals from the population-based Cardiovascular Risk in Young Finns Study (baseline age 32 ± 5 years; 54% women). Insulin resistance was estimated by homeostasis model assessment (HOMA) at baseline and 6-year follow-up. Amino acid associations with HOMA of insulin resistance (HOMA-IR) and glucose were assessed using regression models adjusted for established risk factors. We further examined whether amino acid profiling could augment risk assessment of insulin resistance (defined as 6-year HOMA-IR >90th percentile) in early adulthood.
Isoleucine, leucine, valine, phenylalanine, and tyrosine were associated with HOMA-IR at baseline and for men at 6-year follow-up, while for women only leucine, valine, and phenylalanine predicted 6-year HOMA-IR (P < 0.05). None of the other amino acids were prospectively associated with HOMA-IR. The sum of branched-chain and aromatic amino acid concentrations was associated with 6-year insulin resistance for men (odds ratio 2.09 95% CI 1.38-3.17; P = 0.0005); however, including the amino acid score in prediction models did not improve risk discrimination.
Branched-chain and aromatic amino acids are markers of the development of insulin resistance in young, normoglycemic adults, with most pronounced associations for men. These findings suggest that the association of branched-chain and aromatic amino acids with the risk for future diabetes is at least partly mediated through insulin resistance.
Cardiac involvement accounts for the majority of morbidity and mortality in sarcoidosis. Pathological myocardial fluorodeoxyglucose (FDG)-uptake in positron emission tomography (PET) has been ...associated with cardiovascular events and quantitative metabolic parameters have been shown to add prognostic value. Our aim was to study whether the pattern of pathological cardiac FDG-uptake and quantitative parameters are able to predict cardiovascular events in patients with suspected cardiac sarcoidosis (CS).
137 FDG-PET examinations performed in Tampere University Hospital were retrospectively analyzed visually and quantitatively. Location of pathological uptake was noted and pathological metabolic volume, average standardized uptake value (SUV), and total cardiac metabolic activity (tCMA) were calculated. Patients were followed for ventricular tachycardia, decrease in left ventricular ejection fraction, and death.
Eleven patients had one or more cardiovascular events during the follow-up. Five patients out of 12 with uptake in both ventricles had an event during follow-up. Eight patients had high tCMA (> 900 MBq) and three of them had a cardiovascular event. Right ventricular uptake and tCMA were significantly associated with cardiovascular events during follow-up (P-value .001 and .018, respectively).
High tCMA and right ventricular uptake were significant risk markers for cardiac events among patient with suspected CS.
Background
Exercise electrocardiography is a widely used diagnostic modality for diagnosing coronary artery disease. This method has been used for both sexes; however, its diagnostic accuracy in ...women is limited.
Methods
The study analyzed 332 women participating in the Finnish Cardiovascular Study. Among 332 women, 125 with angiographically proven coronary artery disease (mean age 62.1 ± 9.5 years), 91 with a low likelihood of coronary artery disease (mean age 47.3 ± 13.5 years), and 116 without angiographically proven coronary artery disease (mean age 56.3 ± 9.9 years) were analyzed. The Q, R, S, and ST‐segment changes and QRS score were determined by subtracting the Q, R, S, and ST‐segment amplitudes immediately after the maximal exercise changes from their rest values (Δ). Receiver operating characteristic curve analysis was performed to evaluate the overall diagnostic performance of the parameters for predicting coronary artery disease.
Results
The areas under the receiver operating characteristic curve between coronary artery disease and low likelihood of coronary artery disease groups for the QRS score and ΔSTV5, ΔQaVF, and ΔRaVF were 0.75, 0.73, 0.71, and 0.71, respectively. These areas were lower (0.62, 0.57, 0.60, and 0.60, respectively) between the groups with and without angiographically proven coronary artery disease. QRS score demonstrated the highest sensitivity at 80% specificity (61.5%) and the highest specificity at 80% sensitivity (57.6%).
Conclusions
This study suggests that the QRS and ST‐segment depression have a moderate diagnostic ability to predict coronary artery disease in women. Q and R waves in lead aVF showed good diagnostic ability.
Researchers evaluated the ability of exercise induced QRS score, its composition (Q, R, and S) wave changes and ST‐segment depression in diagnosing coronary artery disease (CAD) in women. They noted that QRS score and ST‐segment depression have a moderate ability to help diagnose CAD, followed by Q and R waves in lead aVF.
apoE, a key regulator of plasma lipids, mediates altered functionalities in lipoprotein metabolism and thus affects the risk of coronary artery disease (CAD). The significance of different apoE ...polymorphisms remains unclear; although the ε4 allele is clearly associated with increased cholesterol levels (which inform CAD risk), direct studies about apoE polymorphisms on CAD risk and development have yielded controversial results. Furthermore, certain species of ceramides—complex lipids abundant in plasma LDL—are markers of increased risk of myocardial infarction and cardiovascular death. Using a high-throughput MS approach, we quantified 30 molecular plasma ceramide species from a cohort of 2,160 apoE-genotyped (rs7412, rs429358) young adults enrolled in the population-based Cardiovascular Risk in Young Finns Study. We then searched this lipidome data set to identify new indications of pathways influenced by apoE polymorphisms and possibly related to CAD risk. This approach revealed a previously unreported association between apoE polymorphism and a consistently documented high-risk CAD marker, Cer(d18:1/16:0). Compared with the apoE ε3/3 reference group, plasma levels of apoE ε4 were elevated and those of apoE ε2 were lowered in all subjects without evidence of apoE-by-sex interactions. apoE associated with seven ceramides that are connected to atherogenically potent macrophages and/or lipoprotein particles; these associations could indicate a plausible linkage between apoE polymorphism and ceramide metabolism, leading to adverse plasma LDL metabolism and atherogenesis. In conclusion, new evidence from plasma ceramides links apoE polymorphism with an increased risk of CAD and extends our understanding of the role of apoE in health and disease.
Abstract Objective MicroRNAs are small non-coding RNAs that inversely regulate their target gene expression. The whole miRNA profile of human atherosclerotic plaques has not been studied previously. ...The aim of this study was to investigate the miRNA expression profile in human atherosclerotic plaques as compared to non-atherosclerotic left internal thoracic arteries (LITA), and to connect this expression to the processes in atherosclerosis. Methods The miRNA expression profiles of six LITAs and 12 atherosclerotic plaques obtained from aortic, carotid, and femoral atherosclerotic arteries from Tampere Vascular Study were analyzed. The analyses were performed with Agilent's miRNA Microarray. The expression levels of over 4-fold up-regulated miRNAs were verified with qRT-PCR from a larger population ( n = 50). Messenger RNA levels were analyzed with Illumina's Expression BeadChip to study miRNA target expression. Results Ten miRNAs were found to be differently expressed in atherosclerotic plaques when compared to controls ( p < 0.05). The expression of miR-21, -34a, -146a, -146b-5p, and -210 was verified and found to be significantly up-regulated in atherosclerotic arteries versus LITAs ( p < 0.001, fold changes 4.61, 2.55, 2.87, 2.82, and 3.92, respectively). Several predicted targets of these miRNAs were down-regulated, and gene set enrichment analysis showed several pathways which could be differently expressed due to this miRNA profile. Conclusions The microRNA expression profile differs significantly between atherosclerotic plaques and control arteries. The most up-regulated miRNAs are involved in processes known to be connected to atherosclerosis. Interfering with the miRNA expression in the artery wall is a potential way to affect atherosclerotic plaque and cardiovascular disease development.
Cardiovascular risk factors, such as high blood pressure, adverse serum lipids, and elevated body mass index in midlife, may harm cognitive performance. It is important to note that longitudinal ...accumulation of cardiovascular risk factors since childhood may be associated with cognitive performance already since childhood, but the previous evidence is scarce. We studied the associations of cardiovascular risk factors from childhood to midlife, their accumulation, and midlife cognitive performance.
From 1980, a population-based cohort of 3596 children (3-18 years of age) have been repeatedly followed up for 31 years. Blood pressure, serum lipids, and body mass index were assessed in all follow-ups. Cardiovascular risk factor trajectories from childhood to midlife were identified using latent class growth mixture modeling. Cognitive testing was performed in 2026 participants 34 to 49 years of age using a computerized test. The associations of the cardiovascular risk factor trajectories and cognitive performance were studied for individual cardiovascular risk factors and cardiovascular risk factor accumulation.
Consistently high systolic blood pressure (β=-0.262 SD 95% CI, -0.520 to -0.005) and serum total cholesterol (β=-0.214 SD 95% CI, -0.365 to -0.064) were associated with worse midlife episodic memory and associative learning compared with consistently low values. Obesity since childhood was associated with worse visual processing and sustained attention (β=-0.407 SD 95% CI, -0.708 to -0.105) compared with normal weight. An inverse association was observed for the cardiovascular risk factor accumulation with episodic memory and associative learning (
for trend=0.008; 3 cardiovascular risk factors: β=-0.390 SD 95% CI, -0.691 to -0.088), with visual processing and sustained attention (
for trend<0.0001; 3 cardiovascular risk factors: β=-0.443 SD 95% CI, -0.730 to -0.157), and with reaction and movement time (
for trend=0.048; 2 cardiovascular risk factors: β=-0.164 SD 95% CI, -0.318 to -0.010).
Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood.
We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns ...Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj) < 0.05) and another two had suggestively significant (p.adj < 0.25) joint association with the two diseases after adjusting for age, sex, body mass index, smoking habit, alcohol consumption, and physical activity. The three most significant member genes from the significant modules were NOSIP, GXYLT2, and TRIM63 (p.adj ≤ 0.18). Genes in the modules were enriched with biological processes that have separately been found to be involved in either bone metabolism or atherosclerosis. The gene modules and their most significant member genes identified in this study support the osteoporosis-atherosclerosis comorbidity hypothesis and can provide new joint biomarkers for both diseases and their dual prevention.
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