Abstract MP070: Genetic Predisposition to High Blood Pressure Associates With Cardiovascular Complications Among Patients With Type 2 Diabetes: Two Independent Studies

Background Hypertension has been associated with an increased risk of cardiovascular disease (CVD).We examined the effect of the genetic predisposition to high blood pressure and its potential interactions with diet and lifestyle factors on risk of cardiovascular complications among diabetic patients. Methods The present study included 1005 men and 1299 women with type 2 diabetes from the Health Professionals Follow-up Study and Nurses’ Health Study: 732 (380 men and 352 women) CVD cases (coronary heart disease [CHD] or stroke) and 1572 non-CVD controls. Genetic predisposition to high blood pressure was estimated by a genetic risk score on basis of 29 blood pressure-predisposing variants identified by a recent GWAS meta-analysis in ∼200,000 Europeans. Results The genetic risk score was associated with prevalent hypertension in both men and women, with a combined OR of 1.07 (95% CI 1.04-1.09) for each additional risk allele. Restricted cubic spline regression analysis indicated a linear relationship between the genetic risk score and increased CVD risk in both men ( P =0.002) and women. ( P =0.028) ( Figure ). The results from the 2 cohorts were combined since the genetic risk score showed consistent associations in men and women. After adjustment for age, BMI, and diet and lifestyle risk factors, each additional risk allele in the genetic risk score was associated with a 5% increased risk of developing CVD (OR 1.05 [95% CI 1.02-1.09]). The OR was 1.49 (1.08-2.07) for CVD when comparing the extreme quartiles of the genetic risk score ( P for trend =0.007). We did not observe significant interactions of the genetic risk score with Dietary Approach to Stop Hypertension diet score, and other lifestyle risk factors such as BMI, physical activity, alcohol intake, use of nonnarcotic analgesics and supplemental folic acid intake. Conclusions Genetic predisposition to high blood pressure is associated with an increased risk of cardiovascular complications in diabetic patients, independent of diet and lifestyle risk factors for hypertension.

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Abstract P259: Genetic Risk Score, Lifestyle Cardiovascular Risk Score, and Myocardial Infarction in Hispanics

Circulation ◽

10.1161/circ.133.suppl_1.p259 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Mercedes Sotos-Prieto ◽

Ana Baylin ◽

Hannia Campos ◽

Lu Qi ◽

Josiemer Mattei

Keyword(s):

Physical Activity ◽

Risk Factors ◽

Myocardial Infarction ◽

Socioeconomic Status ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score ◽

Lifestyle Risk Factors ◽

Cardiovascular Risk Score ◽

Lifestyle Risk

Background: A genetic risk score (GRS) and a lifestyle cardiovascular risk score (LCRS) have been independently associated with myocardial infarction (MI) in Hispanics. However, it is unknown if there is an interaction or a joint association between these scores. Objectives: To assess the interactive and joint associations between a GRS and a LCRS, as well as each individual lifestyle risk factor on the likelihood of MI. Methods: Data included 1534 Costa Rican adults with nonfatal acute MI and 1534 without MI participating in a case-control study. The GRS was calculated by summing the number of the top three MI-associated risk alleles. The LCRS was calculated using the estimated coefficients as weights for each lifestyle risk factors (diet, physical activity, smoking, waist:hip ratio, low or high alcohol intake, and low socioeconomic status). Conditional logistic regression was used to calculate odds ratios (OR), adjusting for age, sex, and area of residence (matching condition), and to test for interaction and joint association. Results: The multivariable OR for MI was 1.14 (95% CI 1.07, 1.22) per GRS unit and 2.72 (2.33, 3.91) per LCRS unit. Participants in the highest tertile of the GRS and highest tertile of the LCRS had higher odds of MI (5.43 [3.80, 7.76]) compared to those in the lowest category. A significant joint association was detected (p <0.0001), while the interaction term was non-significant (p=0.44). Similar results were found for the joint association between GRS and each individual lifestyle component: joint odds for highest risk category vs. lowest was 2.16 (1.53, 3.04) for diet, 1.85 (1.33, 2.59) for physical activity, 3.31 (2.45, 4.48) for smoking, 1.32 (0.92, 1.89) for alcohol, 2.84 (1.82, 4.42) for waist:hip ratio, and 1.86 (1.29, 2.69) for socioeconomic status. Conclusion: Although lifestyle risk factors and genetics contribute independently and in combination to the odds of MI, lifestyle risk factors were stronger among Costa Ricans. Efforts to improve lifestyle behaviors in this population, regardless of genetic susceptibility, may help prevent MI and related heart conditions.

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Genetic Predisposition to High Blood Pressure Associates With Cardiovascular Complications Among Patients With Type 2 Diabetes: Two Independent Studies

Diabetes ◽

10.2337/db12-0225 ◽

2012 ◽

Vol 61 (11) ◽

pp. 3026-3032 ◽

Cited By ~ 8

Author(s):

Q. Qi ◽

J. P. Forman ◽

M. K. Jensen ◽

A. Flint ◽

G. C. Curhan ◽

...

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

High Blood Pressure ◽

Genetic Predisposition ◽

Cardiovascular Complications

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[PP.07.09] GENETIC RISK SCORE AND CARDIOVASCULAR COMPLICATIONS IN PATIENTS WITH HYPERTENSION

Journal of Hypertension ◽

10.1097/01.hjh.0000491760.22026.a9 ◽

2016 ◽

Vol 34 ◽

pp. e155-e156

Author(s):

M. Wirtwein ◽

O. Melander ◽

M. Sjogren ◽

M. Hoffmann ◽

K. Narkiewicz ◽

...

Keyword(s):

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score ◽

Cardiovascular Complications

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Twelve–Single Nucleotide Polymorphism Genetic Risk Score Identifies Individuals at Increased Risk for Future Atrial Fibrillation and Stroke

Stroke ◽

10.1161/strokeaha.114.006072 ◽

2014 ◽

Vol 45 (10) ◽

pp. 2856-2862 ◽

Cited By ~ 64

Author(s):

Hayato Tada ◽

Dov Shiffman ◽

J. Gustav Smith ◽

Marketa Sjögren ◽

Steven A. Lubitz ◽

...

Keyword(s):

Atrial Fibrillation ◽

Single Nucleotide Polymorphism ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Increased Risk

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Genetic Risk Score for Prediction of Newborn Adiposity and Large-for-Gestational-Age Birth

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-4221 ◽

2014 ◽

Vol 99 (11) ◽

pp. E2377-E2386 ◽

Cited By ~ 14

Author(s):

Reeti Chawla ◽

Sylvia E. Badon ◽

Janani Rangarajan ◽

Anna C. Reisetter ◽

Loren L. Armstrong ◽

...

Keyword(s):

Birth Weight ◽

Risk Score ◽

Gestational Age ◽

Genetic Risk ◽

Genetic Risk Score ◽

Large For Gestational Age ◽

Adult Obesity ◽

Maternal Genotype ◽

Increased Risk ◽

Newborn Size

Context: Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes. Objective: This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth. Setting and Design: Single nucleotide polymorphisms (SNPs) in 40 regions associated with adult obesity-related traits were tested for association with newborn size. GRS's for birth weight and sum of skinfolds (SSF) specific to ancestry were calculated using the most highly associated SNP for each ancestry in genomic regions with one or more SNPs associated with birth weight and/or SSF in at least one ancestry group or meta-analyses. Participants: Newborns from the Hyperglycemia Adverse Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern European, 573 Mexican-American, and 1182 Thai). Outcome Measures: Birth weight >90th percentile (LGA) and newborn SSF >90th percentile were primary outcomes. Results: After adjustment for ancestry, sex, gestational age at delivery, parity, maternal genotype, maternal smoking/alcohol intake, age, body mass index, height, blood pressure and glucose, 25 and 23 SNPs were associated (P < .001) with birth weight and newborn SSF, respectively. The GRS was highly associated with both phenotypes as continuous variables across all ancestries (P ≤ 1.6 × 10−19) and improved prediction of birth weight and SSF >90th percentile when added to a baseline model incorporating the covariates listed above. Conclusions: A GRS comprised of SNPs associated with adult obesity-related traits may provide an approach for predicting LGA birth and newborn adiposity beyond established risk factors.

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ISH NIA PS 03-06 Genetic risk score determines cardiovascular complications in patients with stable coronary artery disease

Journal of Hypertension ◽

10.1097/01.hjh.0000500662.32557.62 ◽

2016 ◽

Vol 34 (Supplement 1) ◽

pp. e282

Author(s):

Marcin Wirtwein ◽

Olle Melander ◽

Marketa Sjogren ◽

Michal Hoffmann ◽

Krzysztof Narkiewicz ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score ◽

Stable Coronary Artery Disease ◽

Cardiovascular Complications ◽

Artery Disease

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Mo1732 – Genetic Risk Score to Identify Individuals with an Increased Risk of Colorectal Adenomas

Gastroenterology ◽

10.1016/s0016-5085(19)39016-x ◽

2019 ◽

Vol 156 (6) ◽

pp. S-825

Author(s):

Carla Jerusalen Gargallo-Puyuelo ◽

Patricia Carrera ◽

Angel Lanas ◽

Angel Ferrandez ◽

Enrique Quintero ◽

...

Keyword(s):

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score ◽

Colorectal Adenomas ◽

Increased Risk

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A NEW GENETIC RISK SCORE FOR BLOOD PRESSURE STRONGLY ASSOCIATES WITH THE INCIDENCE OF HYPERTENSION AND CARDIOVASCULAR ENDPOINTS IN TWO SWEDISH COHORTS

Journal of Hypertension ◽

10.1097/01.hjh.0000744412.64941.2c ◽

2021 ◽

Vol 39 (Supplement 1) ◽

pp. e5-e6

Author(s):

Alice Giontella ◽

Marketa Sjögren ◽

Luca Lotta ◽

John Overton ◽

Aris Baras ◽

...

Keyword(s):

Blood Pressure ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score

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Abstract 18093: Bleeding Events in Clopidogrel-Treated Patients with STEMI is Associated with a Genetic Risk Score Based on High-Risk Genetic Polymorphisms

Circulation ◽

10.1161/circ.130.suppl_2.18093 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Jia-Hui Zhang ◽

Jin-Qing Yuan ◽

Xian-Min Meng ◽

Xiao-Fang Tang ◽

Jing Wang ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Major Bleeding ◽

Genetic Risk ◽

Genetic Risk Score ◽

Multivariate Logistic Regression Analysis ◽

Bleeding Events ◽

Genetic Score ◽

Clinical Safety ◽

Increased Risk

Introduction: Gene polymorphisms of ABCB1, CYP2C19, PON1 and P2Y12 may influence pharmacodynamics and clinical events of clopidogrel treatment. Hypothesis: We assessed the hypothesis that a genetic risk score based on identified high-risk single nucleotide polymorphisms (SNPs) would be associated with bleedings in clopidogrel-treated Chinese STEMI patients after percutaneous coronary intervention (PCI). Methods: A total of 503 consecutive patients with STEMI who received an uneventful PCI and were exposed to clopidogrel treatment for 12 months, were enrolled in the single-center registry. There were 38 tag SNPs selected from ABCB1, CYP2C19, PON1 and P2Y12 genes, which were detected by the ligase detection reaction. The primary clinical safety endpoint was the incidence of major bleeding events. Major bleeding was quantified according to bleeding academic research consortium definition (BARC) criteria, including type 3 and 5 in the analysis. The follow-up period was 12 months. Results: Overall, 46 BARC≥3 bleeding events (9.1%) occurred, which included 11 (2.1%) cases of BARC 3b bleedings and 35 (7.0%) cases of BARC 3a bleedings. After adjustment for traditional clinical risk factors, multivariate logistic regression analysis identified SNPs significantly associated with bleedings were ABCB1 (rs1045642, rs2235047, rs7779562), P2Y12 (rs6809699) and CYP2C19*17. A genetic risk score was constructed by summing the number of risk alleles. Bleedings were significantly associated with increased genetic risk score tertile. Patients in the top tertile of the genetic score were estimated to have a 3.268-fold (95%CI=1.198-8.929, p=0.021) increased risk of bleedings compared with those in the bottom tertile. As a continuous variable, the risk score resulted in an OR of 1.326 per unit increase in score (95%CI=1.098-1.601, p=0.003). Conclusions: This genetic score was significantly associated with bleedings after PCI in our study population.

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