scholarly journals Genetic risk score associations for myocardial infarction are comparable in persons with and without rheumatoid arthritis: the population-based HUNT study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
S. Rostami ◽  
M. Hoff ◽  
H. Dalen ◽  
K. Hveem ◽  
V. Videm
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Myocardial Infarction ◽  
Genetic Risk ◽  
Cox Regression ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Multivariable Analysis ◽  
Population Based ◽  
Increased Risk

AbstractPersons with rheumatoid arthritis (RA) have increased risk of myocardial infarction (MI). Overlapping associations with MI of weighted genetic risk scores (wGRS) for coronary artery disease (CAD) and RA is unknown in a population-based setting. Data from the prospective Nord-Trøndelag Health Study (HUNT2: 1995–1997 and HUNT3: 2006–2008) were used. wGRS added each participant’s carriage of all risk variants weighted by the coefficient from published association studies. Published wGRS for CAD and RA were analysed in Cox regression with MI as outcome, age as analysis time, and censoring at the first MI, death, or 31.12.2017. 2609 of 61,465 participants developed MI during follow-up (mean 17.7 years). The best-fitting wGRS for CAD and RA included 157 and 27 single-nucleotide polymorphisms, respectively. In multivariable analysis including traditional CAD risk factors, the CAD wGRS was associated with MI [hazard ratio = 1.23 (95% CI 1.18–1.27) for each SD increase, p < 0.0001] in RA patients (n = 433) and controls. The RA wGRS was not significant (p = 0.06). Independently from traditional risk factors, a CAD wGRS was significantly associated with the risk for MI in RA patients and controls, whereas an RA wGRS was not. The captured genetic risk for RA contributed little to the risk of MI.

Abstract P258: Traditional Risk Factors and a Genetic Risk Score Are Associated with Age of First Acute Coronary Syndrome

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Christopher Labos ◽  
Leo Rui Wang ◽  
Louise Pilote ◽  
Peter Bogaty ◽  
James M Brophy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Acute Coronary Syndrome ◽  
Risk Score ◽  
Genetic Risk ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genome Wide Association Studies ◽  
Coronary Syndrome ◽  
Traditional Risk Factors

Background: Early onset myocardial infarction (MI) is frequently attributed to genetic factors that may accelerate the atherosclerotic process. However, early MI may also occur due to a high burden of traditional risk factors. We sought to examine the association between traditional risk factors as well as a genetic risk score on the age of a first acute coronary syndrome (ACS). Methods and Results: We included 460 participants (mean age 59 +/- 12 years, 22.4% female) with a first ACS enrolled in the Recurrence and Inflammation in the Acute Coronary Syndromes (RISCA) cohort. Participants were genotyped for 30 single nucleotide polymorphisms identified from prior myocardial infarction genome-wide association studies to construct a multilocus genetic risk score (GRS). Linear regression models were fit to estimate the association between traditional risk factors (TRFs) and the GRS with age of first ACS. Several TRFs were significantly associated with earlier age of first ACS (all β coefficients in years; p<0.05 for all) : male sex [β=-6.9 (95%CI -9.7,-4.1)], current cigarette smoking [β=-8.1 (95% confidence interval [CI] -10.0, -6.1)], overweight (BMI>25) [β=-2.6 (95%CI -4.8, -0.3)] and obesity (BMI>30) [β=-5.24 (95%CI -7.9, -2.6)]. Use of hormone replacement therapy [β=-4.3 (95%CI -8.4, -0.3) ] and aspirin use were also associated with age of first ACS [β=3.7 (95%CI 0.3, 7.0)]. After multivariable adjustment for TRFs, a one standard deviation increment in the GRS was associated with a 1.0 (95%CI 0.1-2.0) year earlier age of first ACS. Conclusion: Among individuals with a first ACS, a GRS composed of 30 SNPs is associated with a younger age of presentation. Although common genetic predisposition modestly contributes to earlier ACS, a heavy burden of traditional risk factors is strongly associated with markedly earlier ACS.

scholarly journals Genetic and Environmental Risk Factors for Intracerebral Hemorrhage

Stroke ◽  
2001 ◽  
Vol 32 (suppl_1) ◽  
pp. 321-321
Author(s):  
Daniel Woo ◽  
Laura Sauerbeck ◽  
Brett M Kissela ◽  
Jane C Khoury ◽  
Rakesh Shukla ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intracerebral Hemorrhage ◽  
Environmental Risk ◽  
Multivariable Analysis ◽  
Population Based ◽  
Environmental Risk Factors ◽  
Degree Relative ◽  
Increased Risk ◽  
Apo E ◽  
Apo E Genotype

27 Introduction: We report a planned midpoint analysis of a prospective, population-based, case-control study of the genetic and environmental risk factors of spontaneous, non-traumatic, intracerebral hemorrhage (ICH). Methods: Cases were matched to two controls by age, race and gender. Data was obtained by direct interview and review of all available medical and neuroimaging data. Apolipoprotein E (Apo E)genotype was determined by polymerase chain reaction. Multivariable analyses were performed using logistic regression modeling. Results: Between 6/97 and 2/00, 189 cases of ICH (150 white/39 black; 68 lobar/121 non-lobar) and 368 controls were enrolled into the study. Independent risk factors for multivariable analysis are listed in the table. Only prior stroke was an independent risk factor for both lobar and non-lobar ICH. Conclusions: The importance of individual genetic and environmental risk factors for ICH vary substantially by location of ICH. A history of a first-degree relative with ICH was associated with an increased risk of lobar ICH, independent of Apo E genotype. This finding indicates that other genetic risk factors may be important in the development of ICH.

scholarly journals Combined Effects of MMP-7, MMP-8 and MMP-26 on the Risk of Ischemic Stroke

2019 ◽  
Vol 8 (11) ◽  
pp. 2011
Author(s):  
Fang-I Hsieh ◽  
Hung-Yi Chiou ◽  
Chaur-Jong Hu ◽  
Jiann-Shing Jeng ◽  
Huey-Juan Lin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Weighted Average ◽  
Combined Effects ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk ◽  
Weighted Genetic Risk Score

Ischemic stroke (IS) is multifactorial causation combining with traditional cardiovascular disease (CVD) and genetic risk factors. Combined effects of MMP-7, MMP-8 and MMP-26 on the risk of IS remain incompletely understood. We aimed to assess individual and joint effects for IS risk by weighted genetic risk score (wGRS) from these three genes and traditional CVD risk factors. A case-control study including 500 cases with IS and 500 stroke-free healthy controls frequency-matched with cases by age and sex was conducted. The wGRS was a weighted average of the number of risk genotype across selected SNPs from MMP-7, MMP-8 and MMP-26. Multivariate logistic regression models were used to analyze the relationship between wGRS and risk of IS. A wGRS in the second tertile was associated with a 1.5-fold increased risk of IS compared with the lowest tertile after adjusting for traditional CVD risk factors. Compared to subjects with low genetic and low modifiable CVD risk, those with high genetic and high modifiable CVD risk had the highest risk of IS (adjusted-OR = 5.75). In conclusion, higher wGRS was significantly associated with an increased risk for IS. A significant interaction between genetic and traditional CVD risk factors was also found on the risk of IS.

Incident myocardial infarction associated with major types of arthritis in the general population: a systematic review and meta-analysis

2017 ◽  
Vol 76 (8) ◽  
pp. 1396-1404 ◽  
Author(s):  
Orit Schieir ◽  
Cedomir Tosevski ◽  
Richard H Glazier ◽  
Sheilah Hogg-Johnson ◽  
Elizabeth M Badley
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Meta Analysis ◽  
Population Based ◽  
Case Control Studies ◽  
Increased Risk ◽  
Traditional Risk Factors ◽  
Meta Analyses ◽  
Review Criteria ◽  
Age And Sex

ObjectiveTo synthesise, quantify and compare risks for incident myocardial infarction (MI) across five major types of arthritis in population-based studies.MethodsA systematic search was performed in MEDLINE, EMBASE and CINAHL databases with additional manual/hand searches for population-based cohort or case-control studies published in English of French between January 1980 and January 2015 with a measure of effect and variance for associations between incident MI and five major types of arthritis: rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), gout or osteoarthritis (OA), adjusted for at least age and sex. All search screening, data abstraction quality appraisals were performed independently by two reviewers. Where appropriate, random-effects meta-analysis was used to pool results from studies with a minimum of 10 events.ResultsWe identified a total of 4, 285 articles; 27 met review criteria and 25 criteria for meta-analyses. In studies adjusting for age and sex, MI risk was significantly increased in RA (pooled relative risk (RR): 1.69, 95% CI 1.50 to 1.90), gout (pooled RR: 1.47, 95% CI 1.24 to 1.73), PsA (pooled RR: 1.41, 95% CI 1.17 to 1.69), OA (pooled RR: 1.31, 95% CI 1.01 to 1.71) and tended towards increased risk in AS (pooled RR: 1.24, 95% CI 0.93 to 1.65). Traditional risk factors were more prevalent in all types of arthritis. MI risk was attenuated for each type of arthritis in studies adjusting for traditional risk factors and remained significantly increased in RA, PsA and gout.ConclusionsMI risk was consistently increased in multiple types of arthritis in population-based studies, and was partially explained by a higher prevalence of traditional risk factors in all types of arthritis. Findings support more integrated cardiovascular (CV) prevention strategies for arthritis populations that target both reducing inflammation and enhancing management of traditional CV risk factors.

scholarly journals Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients with Cardiometabolic Disease

Circulation ◽  
2020 ◽  
Author(s):  
Nicholas A. Marston ◽  
Parth N. Patel ◽  
Frederick K. Kamanu ◽  
Francesco Nordio ◽  
Giorgio M. Melloni ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Clinical Risk Factors ◽  
Cardiometabolic Disease ◽  
Clinical Risk ◽  
Hazard Ratios ◽  
Increased Risk

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in five trials across the spectrum of cardiometabolic disease. Methods: Subjects who had consented for genetic testing and who were of European ancestry from the ENGAGE AF-TIMI 48, SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, and FOURIER trials were included in this analysis. A set of 32 SNPs associated with ischemic stroke was used to calculate a GRS in each patient and identify tertiles of genetic risk. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for clinical risk factors. Results: In 51,288 subjects across the five trials, a total of 960 subjects had an ischemic stroke over a median follow-up period of 2.5 years. After adjusting for clinical risk factors, increasing genetic risk was strongly and independently associated with increased risk for ischemic stroke (p-trend=0.009). When compared to individuals in the lowest third of genetic risk, individuals in the middle and top tertiles of genetic risk had adjusted hazard ratios of 1.15 (95% CI 0.98-1.36) and 1.24 (95% CI 1.05-1.45) for ischemic stroke, respectively. Stratification into subgroups revealed the performance of the GRS appeared stronger in the primary prevention cohort with an adjusted HR for the top versus lowest tertile of 1.27 (95% CI 1.04-1.53), compared with an adjusted HR of 1.06 (95% CI 0.81-1.41) in subjects with prior stroke. In an exploratory analysis of patients with atrial fibrillation and CHA 2 DS 2 -VASc of 2, high genetic risk conferred a 4-fold higher risk of stroke and an absolute risk equivalent to those with CHA 2 DS 2 -VASc of 3. Conclusions: Across a broad spectrum of subjects with cardiometabolic disease, a 32-SNP GRS was a strong, independent predictor of ischemic stroke. In patients with atrial fibrillation but lower CHA 2 DS 2 -VASc scores, the GRS identified patients with risk comparable to those with higher CHA 2 DS 2 -VASc scores.

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

Circulation ◽  
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.

The Association Between Genetic Risk Factors and the Size of Intracranial Aneurysms at Time of Rupture

Neurosurgery ◽  
2013 ◽  
Vol 73 (4) ◽  
pp. 705-708 ◽  
Author(s):  
Rachel Kleinloog ◽  
Femke N.G. van 't Hof ◽  
Franciscus J. Wolters ◽  
Ingeborg Rasing ◽  
Irene C. van der Schaaf ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Intracranial Aneurysms ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genetic Risk Factors ◽  
Genome Wide Association Studies ◽  
Aneurysm Size ◽  
Genome Wide

Abstract BACKGROUND: Genetic risk factors for intracranial aneurysms may influence the size of aneurysms. OBJECTIVE: To assess the association between genetic risk factors and the size of aneurysms at the time of rupture. METHODS: Genotypes of 7 independent single-nucleotide polymorphisms (SNPs) of the 6 genetic risk loci identified in genome-wide association studies of patients with intracranial aneurysms were obtained from 700 Dutch patients with an aneurysmal subarachnoid hemorrhage (1997-2007) previously genotyped in the genome-wide association studies; 255 additional Dutch patients with an aneurysmal subarachnoid hemorrhage (2007-2011) were genotyped for these SNPs. Aneurysms were measured on computerized tomography angiography or digital subtraction angiography. The mean aneurysm size (with standard error) was compared between patients with and without a genetic risk factor by the use of linear regression. The association between SNPs and size was assessed for single SNPs and for the combined effect of SNPs by using a weighted genetic risk score. RESULTS: Single SNPs showed no association with aneurysm size, nor did the genetic risk score. CONCLUSION: The 6 genetic risk loci have no major influence on the size of aneurysms at the time of rupture. Because these risk loci explain no more than 5% of the genetic risk, other genetic factors for intracranial aneurysms may influence aneurysm size and thereby proneness to rupture.

scholarly journals Risk Factors for Incident Carotid Artery Revascularization among Older Adults: The Cardiovascular Health Study

2016 ◽  
Vol 6 (3) ◽  
pp. 129-139 ◽  
Author(s):  
Parveen K. Garg ◽  
Willam J.H. Koh ◽  
Joseph A. Delaney ◽  
Ethan A. Halm ◽  
Calvin H. Hirsch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Carotid Artery ◽  
Cardiovascular Health ◽  
Multivariable Analysis ◽  
Population Based ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Increased Risk

Background: Population-based risk factors for carotid artery revascularization are not known. We investigated the association between demographic and clinical characteristics and incident carotid artery revascularization in a cohort of older adults. Methods: Among Cardiovascular Health Study participants, a population-based cohort of 5,888 adults aged 65 years or older enrolled in two waves (1989-1990 and 1992-1993), 5,107 participants without a prior history of carotid endarterectomy (CEA) or cerebrovascular disease had a carotid ultrasound at baseline and were included in these analyses. Cox proportional hazards multivariable analysis was used to determine independent risk factors for incident carotid artery revascularization. Results: Over a mean follow-up of 13.5 years, 141 participants underwent carotid artery revascularization, 97% were CEA. Baseline degree of stenosis and incident ischemic cerebral events occurring during follow-up were the strongest predictors of incident revascularization. After adjustment for these, factors independently associated with an increased risk of incident revascularization were: hypertension (HR 1.53; 95% CI: 1.05-2.23), peripheral arterial disease (HR 2.57; 95% CI: 1.34-4.93), and low-density lipoprotein cholesterol (HR 1.23 per standard deviation [SD] increment [35.4 mg/dL]; 95% CI: 1.04-1.46). Factors independently associated with a lower risk of incident revascularization were: female gender (HR 0.51; 95% CI: 0.34-0.77) and older age (HR 0.69 per SD increment [5.5 years]; 95% CI: 0.56-0.86). Conclusions: Even after accounting for carotid stenosis and incident cerebral ischemic events, carotid revascularization is related to age, gender, and cardiovascular risk factors. Further study of these demographic disparities and the role of risk factor control is warranted.

scholarly journals The Clinical Utility of Genetic Risk Scores Following Myocardial Infarction

2021 ◽  
Author(s):  
◽  
Hadley Northcott
Keyword(s):  
Risk Factors ◽  
New Zealand ◽  
Genetic Risk ◽  
Clinical Utility ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genome Wide Association Studies ◽  
Coronary Syndrome ◽  
Traditional Risk Factors ◽  
Cad Risk

<p>Current risk assessment for the development of coronary artery disease (CAD) in an individual relies on a combination of clinical characteristics. These well-established CAD risk factors include consideration of age, gender, hypertension, dyslipidemia, diabetes, smoking and obesity. However there are a proportion of patients that experience an acute coronary syndrome (ACS) event despite being deemed as low risk based on the current New Zealand risk model. These patients present with an absence of the traditional risk factors, or they fall below the age threshold where CAD screening is initiated.  The lack of association with disease development and presence of the traditional risk factors in these patients has led to the hypothesis that genetics play a significant role in the etiology of their disease. The conduction of family-based hereditary studies has supported the hypothesis that CAD risk is associated with genetic markers. A method of analyzing this genetic risk has been developed in the form of calculating a genetic risk score (GRS). The GRS is comprised of a panel of single nucleotide polymorphisms (SNPs) discovered through genome wide association studies in CAD patients. Currently, there is controversy in the clinical utility of different GRS calculation methods, and as yet, there has been no research conducted on the potential benefits of a GRS in a New Zealand setting.  Our study measured genetic risk through a weighted GRS calculated from a 27 SNP panel in 420 patients in a New Zealand based population. In looking at whether we could determine a difference in GRS values between premature (young) MI patients and older control patients, we found that the mean GRS was not significantly elevated in the premature MI cohort (p = 0.156). However, in assessing GRS differences between ethnicities and in relation to specific risk factors we saw that mean GRS was higher in patients with a family history of coronary disease (p = 0.003), in Māori patients (p = 0.013) and in patients with fewer than 2 traditional risk features (p = 0.001). GRS was not associated with individual traditional risk factors, including dyslipidaemia, hypertension, diabetes, obesity or gender. Our results showed that genetic risk for CAD is identifiable with this GRS, and indicates that further research into ethnic differences and identifying genetic risk in young CAD patients with low traditional risk would provide interesting insights.</p>

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