Coronary Heart Disease In Individuals Research Articles

Possibilities of noninvasive diagnostics of cardiovascular diseases associated with atherosclerosis

Background. Despite the global trend towards a decrease in mortality from cardiovascular pathology of atherosclerotic genesis, this group of diseases continues to occupy a leading position in the structure of disability and mortality among the population of many countries. Aim. Identification of noninvasive markers of arterial wall lesions associated with the presence of arterial hypertension (AH) and coronary heart disease (CHD) in persons younger than 55 years. Materials and methods. The study included 81 people. Three groups were distinguished from them: 1st (n=31) – a control group of practically healthy individuals, average age – 43 (40; 48) years; 2nd group (n=21) – patients with coronary heart disease without a history of cardiovascular diseases (CVD), average age – 45,5±6,1; group 3 (n=29) – patients with AH without CHD, average age – 47 (35; 50) years. The parameters of a biochemical blood test were determined, volumetric sphygmography and a sample with post-occlusive reactive hyperemia were performed. Results. In groups of patients with CHD and AH, negative changes in the lipid profile and higher glucose levels were recorded compared to healthy individuals. According to the results of volumetric sphygmography, the pulse wave velocity in arteries of predominantly elastic type (R/L-PWV) in group 1 was 10.1±1.7 m/s, in group 2 – 12.9±1.8 m/s, in group 3 – 13.1 (12; 14) m/s (р1–2=0.029; р1–30.001); cardio-ankle vascular index (CAVI) – 6.5±0.7, 7.7 (7; 8.7) and 7.8 (7.3; 8.4), respectively (р1–20.001; р1–30.001). According to the data of the test with post-occlusive reactive hyperemia, a comparably high frequency of pathological values of flow-dependent vasodilation (FDV) and reactivity index (RI) was demonstrated in patients with CHD and AH (р1–20.05; р1–30.05). A multifactorial model of noninvasive diagnosis of CHD in individuals without a history of CVD, including non-high-density lipoprotein cholesterol, R/L-PWV, and FDV, has been developed. For patients with AH, glucose, lipid metabolism, R/L-PWV, pulse wave velocity in muscle-type arteries (B-PWV), augmentation index (AI), biological age, CAVI, FDV, RI were the risk factors for the presence of the disease in the anamnesis. Conclusion. The results obtained confirm the importance of an integrated approach in the screening diagnosis of CVD.

Association of plasma proteomics with incident coronary heart disease in individuals with and without type 2 diabetes: results from the population-based KORA study.

Coronary heart disease (CHD) is a major global health concern, especially among individuals with type 2 diabetes (T2D). Given the crucial role of proteins in various biological processes, this study aimed to elucidate the aetiological role and predictive performance of protein biomarkers on incident CHD in individuals with and without T2D. The discovery cohort included 1492 participants from the Cooperative Health Research in the Region of Augsburg (KORA) S4 study with 147 incident CHD cases (45 vs. 102 cases in the group with T2D and without T2D, respectively) during 15.6 years of follow-up. The validation cohort included 888 participants from the KORA-Age1 study with 70 incident CHD cases (19 vs. 51 cases in the group with T2D and without T2D, respectively) during 6.9 years of follow-up. We measured 233 plasma proteins related to cardiovascular disease and inflammation using proximity extension assay technology. Associations of proteins with incident CHD were assessed using Cox regression and Mendelian randomization (MR) analysis. Predictive models were developed using priority-Lasso and were evaluated on top of Framingham risk score variables using the C-index, category-free net reclassification index (cfNRI), and relative integrated discrimination improvement (IDI). We identified two proteins associated with incident CHD in individuals with and 29 in those without baseline T2D, respectively. Six of these proteins are novel candidates for incident CHD. MR suggested a potential causal role for hepatocyte growth factor in CHD development. The developed four-protein-enriched model for individuals with baseline T2D (ΔC-index: 0.017; cfNRI: 0.253; IDI: 0.051) and the 12-protein-enriched model for individuals without baseline T2D (ΔC-index: 0.054; cfNRI: 0.462; IDI: 0.024) consistently improved CHD prediction in the discovery cohort, while in the validation cohort, significant improvements were only observed for selected performance measures (with T2D: cfNRI: 0.633; without T2D: ΔC-index: 0.038; cfNRI: 0.465). This study identified novel protein biomarkers associated with incident CHD in individuals with and without T2D and reaffirmed previously reported protein candidates. These findings enhance our understanding of CHD pathophysiology and provide potential targets for prevention and treatment.

Phytosterol intake and risk of coronary artery disease: Results from 3 prospective cohort studies

BackgroundPhytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol, although their impact on coronary artery disease (CAD) risk remains to be elucidated. ObjectivesThis study aimed to prospectively assess the associations between total and individual phytosterol intake and CAD risk in United States health professionals. MethodsThe analysis included 213,992 participants from 3 prospective cohorts—the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study—without cardiovascular disease or cancer at baseline. Diet was assessed using a validated food frequency questionnaire every 2–4 y since baseline. Associations between phytosterol intake and the risk of CAD, such as nonfatal myocardial infarction and fatal CAD, were evaluated using Cox proportional hazards regression models. ResultsMore than 5,517,993 person-years, 8725 cases with CAD were documented. Comparing extreme quintiles, pooled hazard ratios (95% CIs) of CAD were 0.93 (0.86, 1.01; P-trend = 0.16) for total phytosterols, 0.89 (0.82, 0.96; P-trend = 0.05) for campesterol, 0.95 (0.88, 1.02; P-trend = 0.10) for stigmasterol, and 0.92 (0.85, 1.00; P-trend = 0.09) for β-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and β-sitosterol: the risk reduction plateaued at intakes above ∼180, 30, and 130 mg/d, respectively (P-nonlinearity < 0.001). In a subset of participants (N range between 11,983 and 22,039), phytosterol intake was inversely associated with plasma concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and IL-6 and positively associated with adiponectin, whereas no significant associations were observed for low-density lipoprotein cholesterol or C-reactive protein concentrations. ConclusionsHigher long-term intake of total and major subtypes of phytosterols may be associated with a modest reduction in CAD risk, displaying a nonlinear relationship that plateau at moderate intake levels. The role of phytosterols in preventing CAD warrants further investigation.

Application of machine learning algorithms to construct and validate a prediction model for coronary heart disease risk in patients with periodontitis: a population-based study

BackgroundThe association between periodontitis and cardiovascular disease is increasingly recognized. In this research, a prediction model utilizing machine learning (ML) was created and verified to evaluate the likelihood of coronary heart disease in individuals affected by periodontitis.MethodsWe conducted a comprehensive analysis of data obtained from the National Health and Nutrition Examination Survey (NHANES) database, encompassing the period between 2009 and 2014.This dataset comprised detailed information on a total of 3,245 individuals who had received a confirmed diagnosis of periodontitis. Subsequently, the dataset was randomly partitioned into a training set and a validation set at a ratio of 6:4. As part of this study, we conducted weighted logistic regression analyses, both univariate and multivariate, to identify risk factors that are independent predictors for coronary heart disease in individuals who have periodontitis. Five different machine learning algorithms, namely Logistic Regression (LR), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), and Classification and Regression Tree (CART), were utilized to develop the model on the training set. The evaluation of the prediction models’ performance was conducted on both the training set and validation set, utilizing metrics including AUC (Area under the receiver operating characteristic curve), Brier score, calibration plot, and decision curve analysis (DCA). Additionally, a graphical representation called a nomogram was created using logistic regression to visually depict the predictive model.ResultsThe factors that were found to independently contribute to the risk, as determined by both univariate and multivariate logistic regression analyses, encompassed age, race, presence of myocardial infarction, chest pain status, utilization of lipid-lowering medications, levels of serum uric acid and serum creatinine. Among the five evaluated machine learning models, the KNN model exhibited exceptional accuracy, achieving an AUC value of 0.977. The calibration plot and brier score illustrated the model's ability to accurately estimate probabilities. Furthermore, the model's clinical applicability was confirmed by DCA.ConclusionOur research showcases the effectiveness of machine learning algorithms in forecasting the likelihood of coronary heart disease in individuals with periodontitis, thereby aiding healthcare professionals in tailoring treatment plans and making well-informed clinical decisions.

Association of Fish Oil Supplementation with Risk of Coronary Heart Disease in Individuals with Diabetes and Prediabetes: A Prospective Study in the UK Biobank.

This study aimed to explore the association between habitual intake of fish oil supplementation and the risk of developing CHD in patients with prediabetes and diabetes. Habitual use of fish oil was assessed by repeated questionnaires. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median follow-up of 11.6 years, 4304 and 3294 CHD cases were documented among 47,663 individuals with prediabetes and 22,146 patients with diabetes in the UK Biobank, respectively. After multivariable adjustment, the HRs (95% CI) of CHD were 0.91 (0.85-0.98) and 0.87 (0.80-0.95) for individuals utilizing fish oil supplementation compared with non-users among the participants with prediabetes and diabetes, respectively. Furthermore, we identified an inverse relationship between fish oil use and CHD incidence, which was significantly mediated by serum C-reactive protein (CRP) levels in individuals with prediabetes and by very-low-density lipoprotein cholesterol (VLDL-C) in patients with diabetes at baseline. The inverse associations were consistent in the analyses stratified by potential confounders. In conclusion, the consumption of fish oil supplements was linked to decreased serum CRP and VLDL-C levels and subsequent CHD risk among adults with prediabetes and diabetes. Our findings highlight the important role of the habitual intake of fish oil supplements in preventing CHD in individuals with impaired glucose metabolism.

Abstract 13262: Phytosterol Intake and Risk of Coronary Heart Disease in U.S. Men and Women

Introduction: Phytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol. Evidence regarding dietary phytosterols in relation to coronary heart disease (CHD) risk remains limited. We aimed to prospectively assess the associations between total and individual phytosterol intake and CHD risk in U.S. men and women. Methods: A total of 214,108 men and women from the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study without cardiovascular disease or cancer at baseline were included in the analyses. Diet was assessed using a validated food frequency questionnaire every 2-4 years since baseline. Cox proportional hazards regression models were used to evaluate associations between phytosterol intake and CHD risk. Results: During 5,516,455 person-years of follow-up, 10,152 CHD cases were documented. Comparing extreme quintiles, pooled hazard ratios (HRs) (95% CIs) of CHD were 0.91 (0.85-0.98; P -trend=0.08) for total phytosterols, 0.88 (0.82-0.95; P -trend=0.02) for campesterol, 0.96 (0.90-1.02; P -trend=0.22) for stigmasterol, and 0.91 (0.84-0.98; P -trend=0.03) for beta-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and beta-sitosterol: the risk reduction plateaued at intakes above ~180 mg/day, 30 mg/day, and 130 mg/day, respectively ( P -nonlinearity&lt;0.001). Among 23,543 participants with existing CHD risk markers, phytosterol intake was inversely associated with plasma levels of total cholesterol, triglycerides, C-reactive protein, and interleukin-6, and was positively associated with adiponectin. Phytosterol intake was not associated with LDL or HDL cholesterol levels. Conclusions: Higher long-term intake of total and major subtypes of phytosterols was associated with modest CHD risk reduction, which may plateau at moderate intake levels. The role of phytosterols in preventing CHD needs further investigation.

Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older.

The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events. We used data from 12 792 genotyped, healthy older individuals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. At baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08-1.42], P=0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32-75.24, P=0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15-0.28). A PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction for CHD has clinical utility in individuals aged 70 years and older. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.

Changing maladaptive beliefs among individuals with coronary heart disease using video information

Many individuals with coronary heart disease (CHD) have maladaptive beliefs which might increase anxiety and depression. This study investigates the impact of using video information to convey facts and correct misconceptions about CHD in individuals. 150 individuals with CHD were assigned to either the control group or one of two experimental groups. The participants completed the York Cardiac Beliefs Questionnaire in the baseline measure immediately after first viewing the video (time 1), and after viewing the video for six times within two weeks (time 2). The Beck Anxiety Inventory and Beck Depression Inventory II were completed in the baseline and at time 2. Multiple repeated measures anova shows that after the intervention, participants’ maladaptive beliefs, anxiety and depression were reduced in both experimental groups. Yet, it did not happen in the control group. It indicates that the video information corrects maladaptive beliefs, and reduces anxiety and depression levels in individuals with CHD.

High-Density Lipoprotein Subfractions: Much Ado about Nothing or Clinically Important?

High-density lipoproteins (HDL) are a heterogenous group of plasma molecules with a large variety in composition. There is a wide specter in lipid content and the number of different proteins that has been associated with HDL is approaching 100. Given this heterogeneity and the fact that the total amount of HDL is inversely related to the risk of coronary heart disease (CHD), there has been increasing interest in the function of specific HDL subgroups and in what way measuring and quantifying these subgroups could be of clinical importance in determining individual CHD risk. If certain subgroups appear to be more protective than others, it may also in the future be possible to pharmacologically increase beneficial and decrease harmful subgroups in order to reduce CHD risk. In this review we give a short historical perspective, summarize some of the recent clinical findings regarding HDL subclassifications and discuss why such classification may or may not be of clinical relevance.

Relation between Retinopathy and Progression of Coronary Artery Calcium in Individuals with Versus Without Diabetes Mellitus (From the Multi–Ethnic Study of Atherosclerosis)

Retinopathy is a microvascular complication of diabetes mellitus (DM); however, it is also increasingly recognized in persons without DM. The microvascular diseases may play a prominent role in coronary heart disease (CHD) development in individuals with DM. We performed the study to evaluate the relation between non-DM retinopathy and CHD and also the association between baseline retinopathy and incidence and progression of CHD in individuals with and without DM. We included 5709 subjects with and without DM from the Multi-Ethnic Study of Atherosclerosis, who had retinal photos and coronary artery calcium score (CACS) available. We studied the association between baseline retinopathy and incidence and progression of coronary artery calcification (CAC) in subjects with and without DM. In DM group, the presence of retinopathy was significantly associated with an increased rate of CAC (RR 1.3 (95% CI [1.02, 1.66]) after adjusting for age, sex, race, follow-up time, and CHD risk factors. In non-DM group, the presence of retinopathy was not significantly associated with increased risk of CAC, however, the interaction between presence of retinopathy and DM status was not statistically significant. Within the DM group with CAC present at baseline, the presence of retinopathy was significantly associated with greater CAC progression (113 Agatson units (AU) greater, (95% CI [51-174]). In the non-DM group with present CAC at baseline; the presence of retinopathy was associated with 24 (95% CI [-0.69, 48.76]) AU higher CAC progression. All findings were adjusted for CHD risk factors. In conclusion, after adjustment for major CHD risk factors, retinopathy was associated with progression of CAC in both DM and non-DM individuals. However, the association was stronger in those with DM.

Associations of Serum Nonesterified Fatty Acids With Coronary Heart Disease Mortality and Nonfatal Myocardial Infarction: The CHS (Cardiovascular Health Study) Cohort.

BackgroundSignificant associations have been reported between serum total nonesterified fatty acid (NEFA) concentrations and coronary heart disease (CHD) mortality and incident nonfatal myocardial infarction (MI) in some prospective cohort studies. Little is known about whether individual or subclasses (saturated, polyunsaturated [n‐6 and n‐3], and trans fatty acids) of serum NEFAs relate to CHD mortality and nonfatal MI.Methods and ResultsCHS (Cardiovascular Health Study) participants (N=1681) who had no history of MI, angina, or revascularization or were free of MI at baseline (1996–1997) were included. NEFAs were quantified using gas chromatography. Cox regression analysis was used to evaluate associations of 5 subclasses and individual NEFAs with CHD composite (CHD mortality and nonfatal MI), CHD mortality, and incident nonfatal MI. During a median follow‐up of 11.7 years, 266 cases of CHD death and 271 cases of nonfatal MI occurred. In the fully adjusted model, no significant associations were identified between individual NEFA and CHD composite. Exploratory analyses indicated that lauric acid (12:0) was negatively associated (hazard ratio [HR], 0.76; 95% CI, 0.59–0.98; P=0.0328) and dihomo‐γ‐linolenic acid (20:3n‐6) was positively associated with CHD mortality (HR, 1.34; 95% CI, 1.02–1.76; P=0.0351). Elaidic acid (18:1n‐7t) was positively associated with incident nonfatal MI (HR, 1.46; 95% CI, 1.01–2.12; P=0.0445). No significant associations were observed for NEFA subclass and any outcomes.ConclusionsIn CHS participants, 2 NEFAs, dihomo‐γ‐linolenic and elaidic acids, were positively associated with CHD mortality and nonfatal MI, respectively, suggesting potential susceptibility biomarkers for risks of CHD mortality and nonfatal MI.

Cardiovascular health in early adulthood predicts the development of coronary heart disease in individuals with type 1 diabetes: 25year follow-up from the Pittsburgh Epidemiology of Diabetes Complications study.

Type 1 diabetes increases CHD risk. We examined the use of the American Heart Association's cardiovascular health metrics (blood pressure, total cholesterol, glucose/HbA1c, BMI, physical activity, diet, smoking) to predict incidence of CHD among individuals with type 1 diabetes, with the hypothesis that a better American Heart Association health metric profile would be associated with lower incident CHD. Prevalence of the seven cardiovascular health metrics was determined using first and second visits from adult participants (mean age 28.6years) in the Epidemiology of Diabetes Complications prospective cohort study of childhood-onset type 1 diabetes. An ideal metric score (0-7) was defined as the sum of all metrics within the ideal range, and a total metric score (0-14) was calculated based on poor, intermediate and ideal categories for each metric. Incident CHD development (medical record-confirmed CHD death, myocardial infarction, revascularisation, ischaemic electrocardiogram changes or Epidemiology of Diabetes Complications physician-determined angina) over 25years of follow-up was examined by metric scores. Among 435 participants, BMI, blood pressure, total cholesterol and smoking demonstrated the highest prevalence within the ideal range, while diet and HbA1c demonstrated the lowest. During 25years of follow-up, 177 participants developed CHD. In Cox models, each additional metric within the ideal range was associated with a 19% lower risk (p = 0.01), and each unit increase in total metric score was associated with a 17% lower risk (p < 0.01) of CHD, adjusting for diabetes duration, estimated glomerular filtration rate, albumin excretion rate, triacylglycerols, depression and white blood cell count. Among individuals with type 1 diabetes, higher cardiovascular health metric scores were associated with lower risk of incident CHD. The American Heart Association-defined cardiovascular health metrics provide straightforward goals for health promotion that may reduce CHD risk in the type 1 diabetes population. Graphical abstract.

The association between bacterial infections and the risk of coronary heart disease in type 1 diabetes.

Diabetes increases the risk of infections and coronary heart disease (CHD). Whether infections increase the risk of CHD and how this applies to individuals with diabetes is unclear. To investigate the association between bacterial infections and the risk of CHD in type 1 diabetes. Individuals with type 1 diabetes (n=3781) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. CHD was defined as incident events: fatal or nonfatal myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, identified through national hospital discharge register data. Infections were identified through national register data on all antibiotic purchases from outpatient care. Register data were available from 1 January 1995 to 31 December 2015. Bacterial lipopolysaccharide (LPS) activity was measured from serum samples at baseline. Data on traditional risk factors for CHD were collected during baseline and consecutive visits. Individuals with an incident CHD event (n=370) had a higher mean number of antibiotic purchases per follow-up year compared to those without incident CHD (1.34 [95% CI: 1.16-1.52], versus 0.79 [0.76-0.82], P<0.001), as well as higher levels of LPS activity (0.64 [0.60-0.67], versus 0.58EUmL-1 [0.57-0.59], P<0.001). In multivariable-adjusted Cox proportional hazards models, the mean number of antibiotic purchases per follow-up year was an independent risk factor for incident CHD (HR 1.21, 95% CI: 1.14-1.29, P<0.0001). High LPS activity was a risk factor for incident CHD (HR 1.93 [1.34-2.78], P<0.001) after adjusting for static confounders. Bacterial infections are associated with an increased risk of incident CHD in individuals with type 1 diabetes.

Genotyping 5,10-methylenetetrahydrofolate reductase for patients with coronary artery disease in Southern Taiwan

Hyperhomocysteinaemia has been identified as a risk factor for cerebrovascular, peripheral vascular and coronary heart disease (CAD). Individuals with homozygous MTHFR (5,10-Methylenetetrahydrofolate reductase) mutation have significantly elevated plasma homocysteine levels. Two common mutations in MTHFR (MTHFR 677C→T and MTHFR 1298A→C) may represent an important genetic risk factor in vascular disease. The aim of this research was to investigate these two point mutations of MTHFR for CAD patients and non-CAD controls in Southern Taiwan by PCR-restriction fragment length polymorphism assay. We found that the distribution of the homozygous mutation for MTHFR677 was higher in 54 CAD patients than in 55 non-CAD subjects (11.1% versus 3.6%, P = 0.275). On the other hand, the frequency of MTHFR 1298CC in CAD patients was similar to that of control subjects (P = 1.000). This may suggest there is a trend toward an increased risk of coronary heart disease for individuals that have a 677TT genotype in the Taiwanese population. Finally, the frequency of homozygosity for the two MTHFR common mutations was still low in CAD cases. There may not be an appreciable association of MTHFR mutation to cardiovascular disease in Taiwan. Perhaps a further study including assessment of plasma concentrations of homocysteine, folate and vitamin B12 would be needed to better clarify the relationship between MTHFR polymorphisms and the occurrence of vascular disease.

Sphingomyelin and progression of renal and coronary heart disease in individuals with type 1 diabetes

Aims/hypothesisLipid abnormalities are associated with diabetic kidney disease and CHD, although their exact role has not yet been fully explained. Sphingomyelin, the predominant sphingolipid in humans, is crucial for intact glomerular and endothelial function. Therefore, the objective of our study was to investigate whether sphingomyelin impacts kidney disease and CHD progression in individuals with type 1 diabetes.MethodsIndividuals (n = 1087) from the Finnish Diabetic Nephropathy (FinnDiane) prospective cohort study with serum sphingomyelin measured using a proton NMR metabolomics platform were included. Kidney disease progression was defined as change in eGFR or albuminuria stratum. Data on incident end-stage renal disease (ESRD) and CHD were retrieved from national registries. HRs from Cox regression models and regression coefficients from the logistic or linear regression analyses were reported per 1 SD increase in sphingomyelin level. In addition, receiver operating curves were used to assess whether sphingomyelin improves eGFR decline prediction compared with albuminuria.ResultsDuring a median (IQR) 10.7 (6.4, 13.5) years of follow-up, sphingomyelin was independently associated with the fastest eGFR decline (lowest 25%; median [IQR] for eGFR change: <−4.4 [−6.8, −3.1] ml min−1 [1.73 m−2] year−1), even after adjustment for classical lipid variables such as HDL-cholesterol and triacylglycerols (OR [95% CI]: 1.36 [1.15, 1.61], p < 0.001). Similarly, sphingomyelin increased the risk of progression to ESRD (HR [95% CI]: 1.53 [1.19, 1.97], p = 0.001). Moreover, sphingomyelin increased the risk of CHD (HR [95% CI]: 1.24 [1.01, 1.52], p = 0.038). However, sphingomyelin did not perform better than albuminuria in the prediction of eGFR decline.Conclusions/interpretationThis study demonstrates for the first time in a prospective setting that sphingomyelin is associated with the fastest eGFR decline and progression to ESRD in type 1 diabetes. In addition, sphingomyelin is a risk factor for CHD. These data suggest that high sphingomyelin level, independently of classical lipid risk factors, may contribute not only to the initiation and progression of kidney disease but also to CHD.Graphical abstract

Predictive Utility of Polygenic Risk Scores for Coronary Heart Disease in Three Major Racial and Ethnic Groups

Because polygenic risk scores (PRSs) for coronary heart disease (CHD) are derived from mainly European ancestry (EA) cohorts, their validity in African ancestry (AA) and Hispanic ethnicity (HE) individuals is unclear. We investigated associations of "restricted" and genome-wide PRSs with CHD in three major racial and ethnic groups in the U.S. The eMERGE cohort (mean age 48 ± 14 years, 58% female) included 45,645 EA, 7,597 AA, and 2,493 HE individuals. We assessed two restricted PRSs (PRSTikkanen and PRSTada; 28 and 50 variants, respectively) and two genome-wide PRSs (PRSmetaGRS and PRSLDPred; 1.7M and 6.6M variants, respectively) derived from EA cohorts. Over a median follow-up of 11.1 years, 2,652 incident CHD events occurred. Hazard and odds ratios for the association of PRSs with CHD were similar in EA and HE cohorts but lower in AA cohorts. Genome-wide PRSs were more strongly associated with CHD than restricted PRSs were. PRSmetaGRS, the best performing PRS, was associated with CHD in all three cohorts; hazard ratios (95% CI) per 1 SD increase were 1.53 (1.46-1.60), 1.53 (1.23-1.90), and 1.27 (1.13-1.43) for incident CHD in EA, HE, and AA individuals, respectively. The hazard ratios were comparable in the EA and HE cohorts (pinteraction = 0.77) but were significantly attenuated in AA individuals (pinteraction= 2.9× 10-3). These results highlight the potential clinical utility of PRSs for CHD as well as the need to assemble diverse cohorts to generate ancestry- and ethnicity PRSs.

Polygenic risk for coronary heart disease acts through atherosclerosis in type 2 diabetes

BackgroundType 2 diabetes increases the risk of coronary heart disease (CHD), yet the mechanisms involved remain poorly described. Polygenic risk scores (PRS) provide an opportunity to understand risk factors since they reflect etiologic pathways from the entire genome. We therefore tested whether a PRS for CHD influenced risk of CHD in individuals with type 2 diabetes and which risk factors were associated with this PRS.MethodsWe tested the association of a CHD PRS with CHD and its traditional clinical risk factors amongst individuals with type 2 diabetes in UK Biobank (N = 21,102). We next tested the association of the CHD PRS with atherosclerotic burden in a cohort of 352 genome-wide genotyped participants with type 2 diabetes who had undergone coronary angiograms.ResultsIn the UK Biobank we found that the CHD PRS was strongly associated with CHD amongst individuals with type 2 diabetes (OR per standard deviation increase = 1.50; p = 1.5 × 10− 59). But this CHD PRS was, at best, only weakly associated with traditional clinical risk factors, such as hypertension, hyperlipidemia, glycemic control, obesity and smoking. Conversely, in the angiographic cohort, the CHD PRS was strongly associated with multivessel stenosis (OR = 1.65; p = 4.9 × 10− 4) and increased number of major stenotic lesions (OR = 1.35; p = 9.4 × 10− 3).ConclusionsPolygenic predisposition to CHD is strongly associated with atherosclerotic burden in individuals with type 2 diabetes and this effect is largely independent of traditional clinical risk factors. This suggests that genetic risk for CHD acts through atherosclerosis with little effect on most traditional risk factors, providing the opportunity to explore new biological pathways.

Riesgo cardiovascular en la disminución leve-moderada de la tasa de filtrado glomerular, diabetes y enfermedad coronaria en un área del sur de Europa

Introduction and objectivesIndividuals with mild to moderately decreased estimated glomerular filtration rate (eGFR=30-59 mL/min/1.73 m2) are considered at high risk of cardiovascular disease (CVD). No studies have compared this risk in eGFR=30-59, diabetes mellitus (DM), and coronary heart disease (CHD) in regions with a low incidence of CHD. MethodsWe performed a retrospective cohort study of 122 443 individuals aged 60-84 years from a region with a low CHD incidence with creatinine measured between January 1, 2010 and December 31, 2011. We identified hospital admissions due to CHD (myocardial infarction, angina) or CVD (CHD, stroke, or transient ischemic attack) from electronic medical records up to December 31, 2013. We estimated incidence rates and Cox regression adjusted subdistribution hazard ratio (sHR) including competing risks in patients with eGFR=30-59, DM and CHD, or combinations, compared with individuals without these diseases. ResultsThe median follow-up was 38.3 [IQR, 33.8-42.7] months. Adjusted sHR for CHD in individuals with eGFR=30-59, DM, eGFR=30-59 plus DM, previous CHD, CHD plus DM, and CHD plus eGFR=30-59 plus DM, were 1.34 (95%CI, 1.04-1.74), 1.61 (95%CI, 1.36-1.90), 1.96 (95%CI, 1.42-2.70), 4.33 (95%CI, 3.58-5.25), 7.05 (5.80-8.58) and 7.72 (5.72-10.41), respectively. The corresponding sHR for CVD were 1.25 (95%CI, 1.06-1.46), 1.56 (95%CI, 1.41-1.74), 1.83 (95%CI, 1.50-2.23), 2.86 (95%CI, 2.48-3.29), 4.54 (95%CI, 3.93-5.24), and 5.33 (95%CI, 4.31-6.60). ConclusionsIn 60- to 84-year-olds with eGFR=30-59, similarly to DM, the likelihood of being admitted to hospital for CHD and CVD was about half that of individuals with established CHD. Thus, eGFR=30-59 does not appear to be a coronary-risk equivalent. Individuals with CHD and DM, or eGFR=30-59 plus DM, should be prioritized for more intensive risk management.Full English text available from: www.revespcardiol.org/en

An Unbiased Lipid Phenotyping Approach To Study the Genetic Determinants of Lipids and Their Association with Coronary Heart Disease Risk Factors.

Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4–51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors.

Evaluation of Relationship between Nonalcoholic Fatty Liver and Coronary Artery Disease Severity by Multidetector Computed Tomography

AbstractBackground: Coronary Heart Disease (CHD) is considered to be a leading cause of morbidity and mortality worldwide, so early detection of CHD in asymptomatic individuals is required. Several metabolic risk factors contribute to devel-opment of both Nonalcoholic Fatty Liver Disease (NAFLD) and CHD.Aim of Study: To evaluate the association between (NAFLD) and (CAD) severity.Material and Methods: This study included thirty patients with symptoms suggestive of ischemic heart disease. All patients were subjected to clinical evaluation, coronary CT angiography and Gensini score was used to assess the coronary artery disease severity. Ultrasound examination of the liver to assess the hepatic steatosis.Results: Among thirty patients enrolled in our study 13 patients had positive coronary findings 9 of them showed also hepatic steatosis. The association between NAFLD and CAD was significant as regard the age (p=0.010), BMI (p=0.011). And diabetes mellitus (p=0.011). In comparison with the normal group. There was significant association between Gensini score and grading of fatty liver infiltration (p-value=0.017).Conclusion: There was high prevalence of NAFLD in patients with documented CAD (69.2%) with significant association between Gensini score and grading of fatty liver infiltration.