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.

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.

scholarly journals Cardiovascular risk factor mediation of the effects of education and Genetic Risk Score on cardiovascular disease: a prospective observational cohort study of the Framingham Heart Study

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e045210
Author(s):  
Katie L Powell ◽  
Sebastien R Stephens ◽  
Alexandre S Stephens
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Observational Cohort Study ◽  
Prospective Observational Cohort Study ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Heart Study ◽  
Observational Cohort ◽  
Education Effects

ObjectivesLevel of education and genetic risk are key predictors of cardiovascular disease (CVD). While several studies have explored the causal mechanisms of education effects, it remains uncertain to what extent genetic risk is mediated by established CVD risk factors. This study sought to investigate this and explored the mediation of education and genetic effects on CVD by established cardiovascular risk factors in the Framingham Heart Study (FHS).DesignProspective observational cohort study.Participants7017 participants from the FHS.SettingCommunity-based cohort of adults in Framingham, Massachusetts, USA.Primary outcome measureIncident CVD. The total effects of education and genetic predisposition using a 63-variant genetic risk score (GRS) on CVD, as well as those mediated by established CVD risk factors, were assessed via mediation analysis based on the counterfactual framework using Cox proportional hazards regression models.ResultsOver a median follow-up time of 12.0 years, 1091 participants experienced a CVD event. Education and GRS displayed significant associations with CVD after adjustment for age and sex and the established risk factors smoking, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), body mass index, systolic blood pressure (SBP) and diabetes. For education effects, smoking, HDL-C and SBP were estimated to mediate 18.8% (95% CI 9.5% to 43%), 11.5% (95% CI 5.7% to 29.0%) and 4.5% (95% CI 1.6% to 13.3%) of the total effect of graduate degree, respectively, with the collective of all risk factors combined mediating 38.5% (95% 24.1% to 64.9%). A much smaller proportion of the effects of GRS were mediated by established risk factors combined (17.6%, 95% CI 2.4% to 35.7%), with HDL-C and TC mediating 11.5% (95% CI 6.2% to 21.5%) and 3.1% (95% CI 0.2% to 8.3%), respectively.ConclusionsUnlike education inequalities, established risk factors mediated only a fraction of GRS effects on CVD. Further research is required to elucidate the underlying causal mechanisms of genetic contributions to CVD.

Abstract 13702: A Novel Genetic Risk Score Predicts Ischemic Stroke in Patients With Cardiometabolic Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Parth N Patel ◽  
Nicholas A Marston ◽  
Frederick K Kamanu ◽  
Lu Chen Weng ◽  
Marc P Bonaca ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
European Ancestry ◽  
Cardiometabolic Disease ◽  
Genome Wide Association Studies ◽  
Increased Risk

Introduction: Recent 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 first ischemic stroke after accounting for traditional risk factors in four clinical trials across the spectrum of cardiometabolic disease. Methods: Subjects who had consented for genetic testing, were of European ancestry, and had no prior history of stroke from the SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, and FOURIER trials were included in this analysis. A recently validated GRS composed of 36 SNPs associated with ischemic stroke was calculated in each patient. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for age, sex, ancestry, hypertension, hyperlipidemia, smoking, diabetes mellitus, atrial fibrillation, coronary artery disease, and congestive heart failure. Results: In 23,089 subjects across the four trials, a total of 313 ischemic strokes occurred over a median follow-up of 3 years. Those with higher genetic risk were at significantly increased risk for ischemic stroke with an adjusted HR per 1-SD GRS of 1.12 (1.004-1.25; p=0.043). Individuals in the top 10% of genetic risk had a 42% greater hazard for ischemic stroke than those in the lower 90% of genetic risk (adjusted HR 1.42 [1.03-1.97]; p=0.034). The magnitude of risk conferred by high genetic risk was similar or greater than the risk provided by well-established clinical risk factors (Figure). Conclusions: Across four large clinical trials of subjects with cardiometabolic disease, a 36-SNP GRS was a strong, independent predictor of first ischemic stroke. The risk of stroke was particularly high in patients in the top 10% of genetic risk.

scholarly journals The Use of Sex-Specific Factors in the Assessment of Women’s Cardiovascular Risk

Circulation ◽  
2020 ◽  
Vol 141 (7) ◽  
pp. 592-599 ◽  
Author(s):  
Anandita Agarwala ◽  
Erin D. Michos ◽  
Zainab Samad ◽  
Christie M. Ballantyne ◽  
Salim S. Virani
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Primary Prevention ◽  
American Heart Association ◽  
American Heart ◽  
Heart Association ◽  
The United States ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk

Cardiovascular disease (CVD) is the leading cause of death among women in the United States. As compared with men, women are less likely to be diagnosed appropriately, receive preventive care, or be treated aggressively for CVD. Sex differences between men and women have allowed for the identification of CVD risk factors and risk markers that are unique to women. The 2018 American Heart Association/American College of Cardiology Multi-Society cholesterol guideline and 2019 American College of Cardiology/American Heart Association guideline on the primary prevention of CVD introduced the concept of risk-enhancing factors that are specific to women and are associated with an increased risk of incident atherosclerotic CVD in women. These factors, if present, would favor more intensified lifestyle interventions and consideration of initiation or intensification of statin therapy for primary prevention to mitigate the increased risk. In this primer, we highlight sex-specific CVD risk factors in women, stress the importance of eliciting a thorough obstetrical and gynecological history during cardiovascular risk assessment, and provide a framework for how to initiate appropriate preventive measures when sex-specific risk factors are present.

scholarly journals Progression of retinopathy and incidence of cardiovascular disease: findings from the Chronic Renal Insufficiency Cohort Study

2020 ◽  
pp. bjophthalmol-2019-315333
Author(s):  
Juan E Grunwald ◽  
Maxwell Pistilli ◽  
Gui-Shuang Ying ◽  
Maureen G Maguire ◽  
Ebenezer Daniel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cohort Study ◽  
Renal Insufficiency ◽  
Chronic Renal Insufficiency ◽  
Kidney Diseases ◽  
Vascular Pathology ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk

PurposeChronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD.DesignWe assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average.MethodsUsing standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants’ information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits.ResultsWorsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, p<0.01). After imputation of missing data, these values were OR=1.66 (0.87 to 3.16), p=0.12.ConclusionProgression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD.

Western dietary pattern increases risk of cardiovascular disease in Iranian adults: a prospective population-based study

2017 ◽  
Vol 42 (3) ◽  
pp. 326-332 ◽  
Author(s):  
Parvin Mirmiran ◽  
Zahra Bahadoran ◽  
Azita Zadeh Vakili ◽  
Fereidoun Azizi
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Dietary Patterns ◽  
Dietary Pattern ◽  
Regression Models ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Western Dietary Pattern ◽  
Increased Risk

Limited data are available regarding the association of major dietary patterns and risk of cardiovascular disease (CVD) in Middle Eastern countries. We aimed to evaluate the association of major dietary patterns, using factor analysis, with the risk of CVD. Participants without CVD (n = 2284) were recruited from the Tehran Lipid and Glucose Study and were followed for a mean of 4.7 years. Dietary intake of participants was assessed at baseline (2006–2008); biochemical variables were evaluated at baseline and follow-up examination. Multivariate Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate risk of CVD across tertiles of dietary pattern scores. Linear regression models were used to indicate association of dietary pattern scores with changes of CVD risk factors over the study period. Two major dietary patterns, Western and traditional, were identified. During a mean 4.7 ± 1.4 years of follow-up, 57 participants experienced CVD-related events. In the fully adjusted model, we observed an increased risk of CVD-related events in the highest compared to the lowest tertile category of Western dietary pattern score (HR = 2.07, 95% CI = 1.03–4.18, P for trend = 0.01). Traditional dietary pattern was not associated with incidence of CVD or CVD risk factors. A significant association was observed between the Western dietary pattern and changes in serum insulin (β = 5.88, 95% CI = 0.34–11.4). Our findings confirm that the Western dietary pattern, characterized by higher loads of processed meats, salty snacks, sweets, and soft drinks, is a dietary risk factor for CVD in the Iranian population.

scholarly journals Birthweight in offspring and cardiovascular mortality in their parents, aunts and uncles: a family-based cohort study of 1.35 million births

2019 ◽  
Vol 49 (1) ◽  
pp. 205-215
Author(s):  
Fareeha Shaikh ◽  
Marte Karoline Kjølllesdal ◽  
David Carslake ◽  
Camilla Stoltenberg ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Birth Registry ◽  
Nuclear Families ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Paternal Aunt ◽  
Family Based ◽  
Cvd Mortality

Abstract Background A link between suboptimal fetal growth and higher risk of cardiovascular disease (CVD) is well documented. It has been difficult to assess the contribution of environmental versus genetic factors to the association, as these factors are closely connected in nuclear families. We investigated the association between offspring birthweight and CVD mortality in parents, aunts and uncles, and examined whether these associations are explained by CVD risk factors. Methods We linked Norwegian data from the Medical Birth Registry, the Cause of Death Registry and cardiovascular surveys. A total of 1 353 956 births (1967–2012) were linked to parents and one maternal and one paternal aunt/uncle. Offspring birthweight and CVD mortality association among all relationships was assessed by hazard ratios (HR) from Cox regressions. The influence of CVD risk factors on the associations was examined in a subgroup. Results Offspring birthweight was inversely associated with CVD mortality among parents and aunts/uncles. HR of CVD mortality for one standard deviation (SD) increase in offspring birthweight was 0.72 (0.69–0.75) in mothers and 0.89 (0.86–0.92) in fathers. In aunts/uncles, the HRs were between 0.90 (0.86–0.95) and 0.93 (0.91–0.95). Adjustment for CVD risk factors in a subgroup attenuated all the associations. Conclusions Birthweight was associated with increased risk of CVD in parents and in aunts/uncles. These associations were largely explained by CVD risk factors. Our findings suggest that associations between offspring birthweight and CVD in adult relatives involve both behavioural variables (especially smoking) and shared genetics relating to established CVD risk factors.

scholarly journals Maternal cardiovascular disease risk factors as predictors of preterm birth in California: a case–control study

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e034145
Author(s):  
Anne B. Rohlfing ◽  
Gregory Nah ◽  
Kelli K. Ryckman ◽  
Brittney D. Snyder ◽  
Deborah Kasarek ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Preterm Birth ◽  
Disease Risk ◽  
Case Control ◽  
Chronic Hypertension ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk ◽  
Early Preterm Birth

ObjectiveTo determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth.DesignCase control.SettingCalifornia hospitals.Participants868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010.MethodsLogistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes.Primary outcomePreterm delivery status.ResultsAdjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ2 differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686.ConclusionTraditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women.

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

2018 ◽  
Vol 24 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Peter Riis Hansen
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Inflammatory Diseases ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Chronic Inflammatory Diseases ◽  
Increased Risk ◽  
Shared Risk

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD.

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