scholarly journals Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

2021 ◽  
pp. jech-2020-214358
Author(s):  
Pekka Martikainen ◽  
Kaarina Korhonen ◽  
Aline Jelenkovic ◽  
Hannu Lahtinen ◽  
Aki Havulinna ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Density Lipoprotein ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Increased Risk ◽  
Region Of Residence

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

Primary risk factors influence risk of recurrent myocardial infarction/death from coronary heart disease: results from the Stockholm Heart Epidemiology Program (SHEEP)

2007 ◽  
Vol 14 (4) ◽  
pp. 532-537 ◽  
Author(s):  
Karin Leander ◽  
Björn Wiman ◽  
Johan Hallqvist ◽  
Tomas Andersson ◽  
Anders Ahlbom ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Job Strain ◽  
Enzyme Level ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Increased Risk

Background Prognosis after a first myocardial infarction (MI) is influenced by primary risk factors as well as secondary risk factors. There is still a lack of follow-up studies of well-characterized patient cohorts assessing the relative importance of these factors. Design A cohort of 1635 patients (aged 45-70 years) surviving at least 28 days after a first MI were followed for 6-9 years with regard to recurrent MI/fatal coronary heart disease (CHD). Data were collected through questionnaires, physical examinations, and medical records. Methods Hazard ratios (HR) with 95% confidence intervals (CI) for different risk factors were calculated using the Cox proportional hazard model. Results Of the primary risk factors, diabetes in both sexes was the most important predictor of recurrent MI/fatal CHD, multivariate-adjusted HR in men 1.6 (95% CI; 1.0-2.4) and in women 2.5 (95% CI; 0.9-6.9). Other primary risk factors with prognostic influence were job strain, HR 1.5 (95% CI; 1.0-2.1), and central obesity, HR 1.4 (95% CI; 1.0-2.0), in men and a low level of apolipoprotein A1, HR 2.3 (95% CI; 1.1-5.0), and high-density lipoprotein cholesterol, HR 1.9 (95% CI; 0.9-4.1), in women. The secondary risk factors most detrimental for prognosis were heart failure in men, HR 2.2 (95% CI; 1.2-4.0), and a high peak acute cardiac enzyme level in women, HR 4.4 (95% CI; 2.0-9.7). Conclusions Long-term follow-up of patients who survived at least 28 days after a first MI shows that several primary cardiovascular risk factors, particularly diabetes, contribute to the increased risk of recurrent MI/fatal CHD.

scholarly journals A microRNA panel compared to environmental and polygenic scores for colorectal cancer risk prediction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Janhavi R. Raut ◽  
Ben Schöttker ◽  
Bernd Holleczek ◽  
Feng Guo ◽  
Megha Bhardwaj ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Prediction ◽  
Risk Score ◽  
Characteristic Curve ◽  
Predictive Ability ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Polygenic Scores

AbstractCirculating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a population-based cohort of adults aged 50–75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498–0.616) for the ERS and 0.622 (0.564–0.681) for the PRS.

Abstract P234: Diabetes as Risk Factor for Coronary Heart Disease in Women Compared with Men

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Sanne A Peters ◽  
Rachel R Huxley ◽  
Mark Woodward
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cardiovascular Risk ◽  
Sex Difference ◽  
Prolonged Exposure ◽  
Meta Analysis ◽  
Population Based ◽  
Excess Risk ◽  
Significant Heterogeneity ◽  
Increased Risk

Introduction: A previous pooled analysis suggested that women with diabetes are at substantially increased risk of fatal coronary heart disease (CHD) compared with affected men. Additional findings from larger and more contemporary studies have since published on the sex-specific associations between diabetes and incident CHD. We performed a systematic review with meta-analysis so as to provide the most reliable evidence of any sex difference in the effect of diabetes on subsequent risk of CHD. Methods: PubMed MEDLINE was systematically searched for prospective population-based cohort studies published between on January 1, 1966 and February 13, 2013. Eligible studies had to have reported sex-specific estimates of the relative risk (RR) for incident CHD associated with diabetes, and its associated variability. Random effects meta-analyses with inverse variance weighting were used to obtain sex-specific RRs and their ratio (RRR). Results: Data from 64 cohorts including 858,507 individuals and 28,203 incident CHD events were included. The RR for incident CHD associated with diabetes compared with no diabetes was 2.83 (95% confidence interval [CI]: 2.37, 3.38) in women and 2.11 (95% CI: 1.79, 2.50) in men. The multiple-adjusted RRR for incident CHD was 44% greater in women with diabetes than it was in men with diabetes (95% CI: 27; 63) with no significant heterogeneity between studies (I2=20%). Conclusions: Women with diabetes have more than a 40% greater risk of incident CHD compared with men with diabetes. Sex disparities in pharmacotherapy are unlikely to explain the excess risk in women. Instead, a greater deterioration in cardiovascular risk profile combined with more prolonged exposure to adverse levels of cardiovascular risk factors among pre-diabetic women compared with their male equivalents may be responsible for the excess risk of diabetes-related CHD in women. Future studies are warranted elucidate the mechanisms responsible for the substantial sex-difference in diabetes-related risk of CHD.

scholarly journals Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults

2020 ◽  
Vol 27 (15) ◽  
pp. 1617-1626 ◽  
Author(s):  
Roshni Joshi ◽  
S Goya Wannamethee ◽  
Jorgen Engmann ◽  
Tom Gaunt ◽  
Deborah A Lawlor ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Odds Ratio ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Increased Risk ◽  
The Individual

Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. Conclusions Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

6074Cardiorespiratory fitness, socioeconomic status and mortality in middle-aged men: a population-based prospective cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Y Jae ◽  
S Kurl ◽  
B A Franklin ◽  
J Choo ◽  
H J Kim ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Heart Disease ◽  
Density Lipoprotein ◽  
Population Based ◽  
Lipoprotein Cholesterol ◽  
Low Ses ◽  
Risk Of Death ◽  
Increased Risk ◽  
Material Standard Of Living ◽  
Cvd Mortality

Abstract Background Although both low socioeconomic status (SES) and poor cardiorespiratory fitness (CRF) are associated with increased chronic disease and a heightened risk of death, it remains unclear whether moderate-to-high levels of CRF confer survival benefits in low SES populations. Purpose The present study evaluated the hypothesis that SES and CRF predict all-cause mortality (ACM), cardiovascular disease (CVD) mortality and sudden cardiac death (SCD), and that moderate-to-high levels of CRF may attenuate the associations between low SES and adverse cardiovascular outcomes. Methods This prospective study was based on a population-based sample of 2,368 men aged 42 to 61 years, who were followed in the Kuopio Ischemic Heart Disease cohort. CRF was directly measured by peak oxygen uptake (VO2peak) during progressive exercise testing to volitional fatigue. SES was characterized using self-reported questionnaires via combined measures of income, education, occupation, occupational prestige, material standard of living, and housing conditions. CRF and SES were divided into tertiles, and 4 combined groups (Fit-high SES, Fit-low SES, Unfit-high SES, and Unfit-low SES) based on the median values of CRF and SES. Results During a 25 year median follow-up (interquartile ranges: 18–27 years), 1116 ACM, 512 CVD mortality and 221 SCD events occurred. After adjusting for potential confounders (age, smoking, alcohol, body mass index, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, diabetes, hypertensive medication, family history of coronary heart disease, and physical activity), the lowest levels of SES were at significantly increased risk for ACM (hazard ratio (HR) 1.49, 95% Confidence Interval (CI): 1.30–1.71), CVD mortality (HR 1.38, 1.13–1.69) and SCD (HR 1.34, 0.97–1.84). In contrast, higher levels of CRF were associated with lower risks of ACM (HR 0.56, 0.46–0.67), CVD mortality (HR 0.53, 0.40–0.71) and SCD (HR 0.53, 0.34–0.83). In combined associations of SES and CRF with mortality, unfit-low SES had significantly higher risks of ACM (HR 2.12, 1.75–2.57), CVD mortality (HR 2.20, 1.64–2.94) and SCD (HR 2.95, 1.79–4.86), but fit-low SES was not associated with a heightened risk of cardiovascular mortality or SCD (CVD mortality, 1.03, 0.73–1.46; SCD, 1.54, 0.87–2.72) as compared with their fit-high SES counterparts (reference). Conclusion Our findings indicate that both SES and CRF are independently associated with the risk of death; however, moderate-to-high levels of CRF appear to attenuate the risk of CVD mortality and SCD in low SES men. These unique data have important implications for public health interventions designed to enhance survival in underserved population cohorts.

Gene-diet interaction and plasma lipid responses to dietary intervention

2002 ◽  
Vol 30 (2) ◽  
pp. 68-73 ◽  
Author(s):  
J. M. Ordovas
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Successful Aging ◽  
Dietary Intervention ◽  
Dietary Habits ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Dietary Recommendations ◽  
Dietary Pufa ◽  
Increased Risk

Strategies for disease prevention can have a major impact on people's health. However, major gaps exist in our knowledge with regard to nutritional adequacy, nutrient-disease interactions, nutrient-gene interactions, and effective strategies for implementation of dietary recommendations which have the potential to decrease the disease burden and to contribute to successful aging of the population. Coronary heart disease is one of the major causes of mortality in the world. We have sound evidence that high levels of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased risk of coronary heart disease. Lipoprotein concentrations are associated with environmental variables such as diet and lifestyle, but genetics also play a significant role. We have examined polymorphisms at candidate loci to determine their usefulness as markers for dietary responses. A G/A polymorphism 75 bp upstream from the gene encoding apolipoprotein AI (APOA1) has been described in ~ 30% of the population. Our studies show that this polymorphism is associated with variability in the HDL-C response to dietary fat, specifically to polyunsaturated fatty acids (PUFA) in the diet. Carriers of the A allele respond to increases in dietary PUFA with elevations in HDL-C levels, probably due to altered interactions of transcription factors with the mutated promoter. Therefore carriers of the A allele can potentially decrease their atherogenic risk by consuming high-PUFA diets. Likewise, we have examined the interaction between other dietary habits, such as alcohol drinking, and variability at the APOE locus, and have demonstrated that the classical associations between APOE polymorphism and LDL-C levels are observed primarily in those subjects who consume alcohol. Moreover, we have found a subgroup of the population, APOE4 carriers, for whom drinking alcohol may exert detrimental effects on lipid metabolism. This knowledge will contribute towards the development of more effective personalized dietary recommendations.

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