scholarly journals Genomic prediction of coronary heart disease

2016 ◽  
Author(s):  
Gad Abraham ◽  
Aki S Havulinna ◽  
Oneil G Bhalala ◽  
Sean G Byars ◽  
Alysha M de Livera ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Meta Analysis ◽  
Risk Scores ◽  
Individual Risk ◽  
Clinical Risk ◽  
Framingham Risk ◽  
Chd Risk ◽  
Genomic Risk

Background Genetics plays an important role in coronary heart disease (CHD) but the clinical utility of a genomic risk score (GRS) relative to clinical risk scores, such as the Framingham Risk Score (FRS), is unclear. Methods We generated a GRS of 49,310 SNPs based on a CARDIoGRAMplusC4D Consortium meta-analysis of CHD, then independently tested this using five prospective population cohorts (three FINRISK cohorts, combined n=12,676, 757 incident CHD events; two Framingham Heart Study cohorts (FHS), combined n=3,406, 587 incident CHD events). Results The GRS was strongly associated with time to CHD event (FINRISK HR=1.74, 95% CI 1.61-1.86 per S.D. of GRS; Framingham HR=1.28, 95% CI 1.18-1.38), and was largely unchanged by adjustment for clinical risk scores or individual risk factors, including family history. Integration of the GRS with clinical risk scores (FRS and ACC/AHA13 score) improved prediction of CHD events within 10 years (meta-analysis C-index: +1.5-1.6%, P<0.001), particularly for individuals ≥60 years old (meta-analysis C-index: +4.6-5.1%, P<0.001). Men in the top 20% of the GRS had 3-fold higher risk of CHD by age 75 in FINRISK and 2-fold in FHS, and attaining 10% cumulative CHD risk 18y earlier in FINRISK and 12y earlier in FHS than those in the bottom 20%. Furthermore, high genomic risk was partially compensated for by low systolic blood pressure, low cholesterol level, and non-smoking. Conclusions A GRS based on a large number of SNPs substantially improves CHD risk prediction and encodes decades of variation in CHD risk not captured by traditional clinical risk scores.

Effect of dietary modification by calorie restriction on cholesterol levels in lipoprotein(a) and other lipoprotein classes

2016 ◽  
Vol 54 (5) ◽  
pp. 567-576 ◽  
Author(s):  
Yuji Hirowatari ◽  
Daisuke Manita ◽  
Keiko Kamachi ◽  
Akira Tanaka
Keyword(s):  
Body Mass Index ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Calorie Restriction ◽  
Framingham Risk Score ◽  
Dietary Modification ◽  
Lipoprotein A ◽  
Cholesterol Levels ◽  
Framingham Risk

Background Dietary habits are associated with obesity which is a risk factor for coronary heart disease. The objective is to estimate the change of lipoprotein(a) and other lipoprotein classes by calorie restriction with obesity index and Framingham risk score. Methods Sixty females (56 ± 9 years) were recruited. Their caloric intakes were reduced during the six-month period, and the calorie from fat was not more than 30%. Lipoprotein profiles were estimated at baseline and after the six-month period of calorie restriction. Cholesterol levels in six lipoprotein classes (HDL, LDL, IDL, VLDL, chylomicron and lipoprotein(a)) were analysed by anion-exchange liquid chromatography. The other tests were analysed by general methods. Additionally, Framingham risk score for predicting 10-year coronary heart disease risk was calculated. Results Body mass index, waist circumference, insulin resistance, Framingham risk score, total cholesterol, LDL-cholesterol and IDL-cholesterol were significantly decreased by the calorie restriction, and the protein and cholesterol levels of lipoprotein(a) were significantly increased. The change of body mass index was significantly correlated with those of TC, VLDL-cholesterol and chylomicron-cholesterol, and that of waist circumference was significantly correlated with that of chylomicron-cholesterol. The change of Framingham risk score was significantly correlated with the change of IDL-C. Conclusion Obesity indexes and Framingham risk score were reduced by the dietary modification. Lipoprotein profile was improved with the reduction of obesity indexes, but lipoprotein(a) was increased. The changes of obesity indexes and Framingham risk score were related with those of triglyceride-rich lipoproteins, e.g. IDL, VLDL and CM.

Abstract 16508: Effect of Disclosure of Genetic Risk for Coronary Heart Disease on Information Seeking and Information Sharing in a Randomized Clinical Trial (from the MI-GENES Investigators)

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Sherry-Ann Brown ◽  
Hayan Jouni ◽  
Erin Austin ◽  
Tariq Marroush ◽  
Iftikhar Kullo ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Information Sharing ◽  
Risk Score ◽  
Information Seeking ◽  
Genetic Risk ◽  
Heart Attack ◽  
Internet Use ◽  
Risk Disclosure ◽  
Chd Risk

Background: Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. Methods: The myocardial infarction genes (MI-GENES) trial randomized participants aged 45-65 years who were at intermediate risk for CHD based on conventional risk factors and not on statins, to receive their conventional risk score (CRS) or their CRS plus a genetic risk score (GRS) based on 28 susceptibility variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys to assess information seeking (including internet use and accessing electronic health records (EHR)) were completed before and three and six months after risk disclosure. Information sharing parameters were assessed after risk disclosure. We assessed whether these behaviors differed by GRS disclosure, or by high (≥1.1) or low (<1.1) GRS. Adjustments were made for age, sex, family history of CHD, baseline CRS and GRS, and education. Results were reported as the mean difference (and standard error) in the score for each survey response between the GRS and CRS participants, with significance determined by regression analysis. Results: GRS participants accessed their EHR to obtain information related to their CHD risk more than CRS participants (0.14 ± 0.06, p=0.03). Overall internet use (0.61 ± 0.23, p=0.01), as well as internet use to seek information about heart disease (0.14 ± 0.06, p=0.02) and how genetic factors affect risk of having a heart attack (0.23 ± 0.07, p=0.002), was significantly higher in the GRS participants. GRS participants shared information about heart attack risk with others (0.35 ± 0.13, p=0.007), particularly family members (0.1 ± 0.04, p=0.02), (V4: 0.10 ± 0.05, p=0.05), and their primary care provider (V4: 0.15 ± 0.07, p=0.03) more than CRS participants. Internet use, EHR access, and information sharing did not differ significantly between the high and low GRS groups. Conclusions: Disclosure of GRS for CHD resulted in greater information seeking (including internet use and EHR access) and information sharing by study participants. Disclosure of genetic risk for CHD may help advance patient engagement in precision medicine.

Effect of soluble-viscous dietary fibre on coronary heart disease risk score across 3 population health categories: data from randomized, double-blind, placebo-controlled trials

2020 ◽  
Vol 45 (7) ◽  
pp. 801-804
Author(s):  
Vladimir Vuksan ◽  
John L. Sievenpiper ◽  
Elena Jovanovski ◽  
Alexandra L. Jenkins ◽  
Allison Komishon ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Coronary Heart Disease Risk ◽  
Disease Risk ◽  
Blood Cholesterol ◽  
Double Blind ◽  
Framingham Risk ◽  
Heart Disease Risk

We applied the Framingham risk equation in healthy, metabolic syndrome, and diabetes populations, following treatment with viscous fibre from konjac-based blend (KBB). KBB yielded reduction in estimated risk score by 16% (1.04 ± 0.03 vs. 0.87 ± 0.04, p < 0.01) in type 2 diabetes, 24% (1.08 ± 0.01 vs. 0.82 ± 0.02, p < 0.01) in metabolic syndrome, and 25% (1.09 ± 0.05 vs. 0.82 ± 0.06, p < 0.01) in healthy individuals. Drivers for decreased risk were improvements in blood cholesterol and systolic blood pressure. The composite coronary heart disease risk across populations was reduced 22% (p < 0.01). Novelty Viscous fibre from konjac-xanthan reduced 10-year relative coronary heart disease using Framingham Risk Score across the glycemic status spectrum.

scholarly journals Chromosome 9p21.3 Coronary Heart Disease Locus Genotype and Prospective Risk of CHD in Healthy Middle-Aged Men

2008 ◽  
Vol 54 (3) ◽  
pp. 467-474 ◽  
Author(s):  
Philippa J Talmud ◽  
Jackie A Cooper ◽  
Jutta Palmen ◽  
Ruth Lovering ◽  
Fotios Drenos ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Effect Size ◽  
Nucleotide Polymorphisms ◽  
Framingham Risk ◽  
Chd Risk ◽  
Heart Study ◽  
History Of ◽  
Future Events ◽  
Prospective Risk

Abstract Background: We investigated whether chromosome 9p21.3 single-nucleotide polymorphisms (SNPs), identified in coronary heart disease (CHD) genome-wide association scans, added significantly to the predictive utility for CHD of conventional risk factors (CRF) in the Framingham risk score (FRS) algorithm. Methods: In the Northwick Park Heart Study II of 2742 men (270 CHD events occurring during a 15-year prospective study), rs10757274 A&gt;G [mean frequency G = 0.48 (95% CI 0.47–0.50)] was genotyped. Using the area under the ROC curve (AROC) and the likelihood ratio (LR) statistic, we assessed the discriminatory performance of the FRS based on CRFs with and without genotype. Results: rs10757274 A&gt;G was associated with incident CHD, with an effect size as reported previously [hazard ratio in GG vs AA men of 1.60 (95% CI 1.12–2.28)], independent of CRFs and family history of CHD. Although the AROC for CRFs alone [0.62 (95% CI 0.58–0.66)] did not increase significantly (P = 0.14) when rs10757274 A&gt;G genotype was added [0.64 (95% CI 0.60–0.68)], including genotype gave better fit (LR P = 0.01) and including rs10757274 moved 369 men (13.5% of the total) into more accurate risk categories. To model polygenic effects, 10 hypothetical, randomly assigned gene variants, with similar effect size and frequencies were added. Two variants made significant AROC improvements to the FRS prediction (P = 0.01), whereas further variants had smaller incremental effects (final AROC = 0.71, P &lt;0.001 vs CRFs; LR vs CRFs P &lt;0.0001). Conclusions: Although overall, rs10757274 did not add substantially to the usefulness of the FRS for predicting future events, it did improve reclassification of CHD risk, and thus may have clinical utility.

Heterogeneity of the Predictive Polygenic Risk Scores for Coronary Heart Disease Age-at-onset in Three Different CHD Family-based Ascertainments

2021 ◽  
Author(s):  
Mary F. Feitosa ◽  
Allison L. Kuipers ◽  
Mary K. Wojczynski ◽  
Lihua Wang ◽  
Emma Barinas-Mitchell ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Family History ◽  
High Risk ◽  
Healthy Aging ◽  
Age At Onset ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Chd Risk ◽  
Family Based

Background - Polygenic risk scores (PRS) for coronary heart disease (CHD) may contribute to assess the overall risk of CHD. We evaluated how PRS may influence CHD risk when the distribution of age-at-onset, sex, and family health history differ significantly. Methods - Our study included three family-based ascertainments: Long Life Family Study (LLFS, N Individuals =4,572), which represents a low CHD risk, and Family Heart Study, which consists of randomly selected families (FamHS-Random, N Individuals =1,806), and high CHD risk families (FamHS-High Risk, N Individuals =2,301). We examined the effects of PRS, sex, family ascertainment, PRS interaction with sex (PRS*Sex) and with family ascertainment (PRS*LLFS and PRS*FamHS-High Risk) on CHD, corrected for traditional cardiovascular risk factors using Cox proportional hazard regression models. Results - Healthy-aging LLFS presented ~17 years delayed for CHD age-at-onset compared with FamHS-High Risk ( P <1.0x10 -4 ). Sex-specific association ( P <1.0x10 -17 ) and PRS*Sex ( P =2.7x10 -3 ) predicted prevalent CHD. CHD age-at-onset was associated with PRS (HR=1.57, P =1.3x10 -5 ), LLFS (HR=0.54, P =2.6x10 -5 ) and FamHS-High Risk (HR=2.86, P =6.70x10 -15 ) in men, and with PRS (HR=1.76, P =7.70x10 -3 ), FamHS-High Risk (HR=4.88, P =8.70x10 -10 ) and PRS*FamHS-High Risk (HR=0.61, P =3.60x10 -2 ) in women. In the PRS extreme quartile distributions, CHD age-at-onset was associated ( P <0.05) with PRS, FamHS-High Risk, and PRS interactions with both low and high CHD risk families for women. For men, the PRS quartile results remained similar to the whole distribution. Conclusions - Differences in CHD family-based ascertainments show evidence of PRS interacting with sex to predict CHD risk. In women, CHD age-at-onset was associated with PRS, CHD family history, and interactions of PRS with family history. In men, PRS and CHD family history were the major effects on the CHD age-at-onset. Understanding the heterogeneity of risks associated with CHD endpoints at both the personal and familial levels may shed light on the underlying genetic effects influencing CHD and lead to more personalized risk prediction.

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