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.

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.

Gestational Trophoblastic Neoplasia From Genetically Confirmed Hydatidiform Moles: Prospective Observational Cohort Study

2018 ◽  
Vol 28 (9) ◽  
pp. 1772-1780 ◽  
Author(s):  
Hirokazu Usui ◽  
Jia Qu ◽  
Asuka Sato ◽  
Zijun Pan ◽  
Akira Mitsuhashi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Laboratory Data ◽  
Spontaneous Remission ◽  
Observational Cohort Study ◽  
Polymorphism Analysis ◽  
Prospective Observational Cohort Study ◽  
Gestational Trophoblastic Neoplasia ◽  
Observational Cohort ◽  
Hydatidiform Moles

ObjectiveThe aim of this study was to evaluate the incidence and risk factors of gestational trophoblastic neoplasia (GTN) from hydatidiform moles (HMs) cytogenetically diagnosed in a prospective cohort setting.MethodsThe prospective observational cohort study included cases of cytogenetically defined molar pregnancies, which were diagnosed by a multiplex short tandem repeat polymorphism analysis. Cases were classified as androgenetic complete HMs (CHMs), diandric monogynic triploid partial HMs (PHMs), or biparental abortion. Gestational trophoblastic neoplasia was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 criteria. Incidences for each category, that is, CHM, PHMs, and biparental abortion, were calculated. Clinical variables (age, partner age, gravidity, parity, height, weight, BMI, and gestational age) and laboratory data (serum human chorionic gonadotropin [hCG], white blood cell count, hemoglobin, and platelet count) were compared between spontaneous remission cases and GTN cases in androgenetic CHMs.ResultsAmong 401 cases, 380 were classified as follows: 232 androgenetic CHMs, 60 diandric monogynic PHMs, and 88 biparental abortions. A total of 35 cases (15.1%) of CHMs, but only 1 case of PHM (1.7%) and no biparental abortions, exhibited progression to GTN. The hCG value before evacuation was significantly higher in GTN cases than in spontaneous remission cases (P = 0.001, Kruskal-Wallis test). Patient age was also significantly higher in GTN cases than in spontaneous remission cases (P = 0.002, Student t test).ConclusionsUnder the cohort cytogenetic diagnosis setting, the traditional risk factors for GTN after molar pregnancy, hCG value before evacuation and age, were confirmed in androgenetic CHMs. The risk of GTN was lower for PHMs than for CHMs. However, 1 patient with cytogenetic PHMs developed into GTN.

scholarly journals The contribution of stress to the social patterning of clinical and subclinical CVD risk factors in African Americans: The Jackson Heart Study

2012 ◽  
Vol 75 (9) ◽  
pp. 1697-1707 ◽  
Author(s):  
Samson Y. Gebreab ◽  
Ana V. Diez-Roux ◽  
DeMarc A. Hickson ◽  
Shawn Boykin ◽  
Mario Sims ◽  
...  
Keyword(s):  
Risk Factors ◽  
African Americans ◽  
Jackson Heart Study ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Heart Study ◽  
The Social ◽  
Subclinical Cvd

scholarly journals Increased percentage of PD-L1+ natural killer cells predicts poor prognosis in sepsis patients: a prospective observational cohort study

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Wenqiang Jiang ◽  
Xusheng Li ◽  
Miaoyun Wen ◽  
Xiaoyu Liu ◽  
Kangrong Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cell Death ◽  
Cohort Study ◽  
Programmed Cell Death ◽  
Nk Cells ◽  
Observational Cohort Study ◽  
Prospective Observational Cohort Study ◽  
Combination Model ◽  
Observational Cohort ◽  
Independent Risk Factors

Abstract Background Natural killer (NK) cells play a major role in immune tolerance after sepsis, and the programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) system mediates evasion of host immunity. The correlation between PD-L1 levels in NK cells and the prognosis of patients with sepsis, however, has not been elucidated. Thus, it was hypothesized that PD-L1 in NK cells could be a novel biomarker of the mortality for sepsis patients. Methods A prospective, observational, cohort study in a general intensive care unit had earlier enrolled patients according to the sepsis-3 criteria, and peripheral blood samples were collected within 24 h post-recruitment. The expression of four co-signaling molecules (PD-1, CD28, PD-L1, and CD86) in NK cells was assayed, and the sequential organ failure assessment (SOFA) scores were recorded on day 1. Patients were followed up until 28 days. Multivariate regression analysis assessed the independent risk factors for 28-day mortality. The association between biomarkers and 28-day mortality was assessed by Cox regression survival analysis. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis. Results A total of 269 patients were recruited, and 114 patients were finally included for final analysis. Of these, 30 (26.3%) patients died during 28 days. The percentage of PD-L1+ NK cells (OR 1.022; 95% CI 1.002–1.043) and SOFA scores (OR 1.247; 95% CI 1.092–1.424) were independent risk factors for 28-day mortality. The AUC of the percentage of PD-L1+ NK cells, SOFA scores, and their combination model were 0.655 (0.559–0.742), 0.727 (0.635–0.807) and 0.808 (0.723–0.876), respectively. The combination model was the indicator with the best AUC to predict mortality in 28 days (all p < 0.05). Patients with the percentage of PD-L1+ NK cells above the cutoff point 5.58% (hazard ratio (HR) 10.128 (1.372–74.772), p = 0.001), and the combination model prediction possibility above 0.1241 (HR 13.730 (3.241–58.158), p < 0.001) were the indexes that had greater discriminative capacity to predict 28 days mortality. Conclusions The percentage of PD-L1+ NK cells at admission serves as a novel prognostic biomarker for predicting mortality and contributes to improve the predictive capacity of SOFA score in patients with sepsis.

Abstract P291: Psychosocial Factors are Associated with Cardiovascular Disease among African Americans in the Jackson Heart Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Mario Sims ◽  
Marino Bruce ◽  
Sharon Wyatt ◽  
Tom Mosley ◽  
Daniel Sarpong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Negative Affect ◽  
Psychosocial Factors ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Major Life Events ◽  
Major Life ◽  
Heart Study ◽  
The Mean ◽  
Global Stress

Introduction: African Americans (AA) have a higher risk for cardiovascular disease (CVD) than Whites. This disparity has been attributed to risk factors such as hypertension, diabetes, and obesity. This disparity has also been attributed to psychosocial factors across groups. Using Jackson Heart Study (JHS) data, we examined the associations of negative affect and stress measures with CVD risk factors and prevalent CVD among AA. Hypothesis: Negative affect and stress measures are associated with prevalent CVD risk factors and CVD among men and women in the JHS. Methods: Cross-sectional associations of negative affect (cynicism, anger in, anger out, and depressive symptoms) and stress (global stress, weekly stress, and major life events) with prevalent BMI, hypertension, diabetes and CVD were examined among 5,301 participants 34-85 years old (women=3,360; men=1,941). We estimated mean differences in BMI and prevalence ratios (PR) of hypertension, diabetes and CVD with measures of negative affect and stress and adjusted for demographic and clinical risk factors. Results: Men had higher cynical distrust and anger in scores than women (p<.05). Women had higher depressive symptoms, global stress, weekly stress and major life event scores than men (p<.05). After adjustment for age, sex, education, behaviors and risk factors, each psychosocial factor (except anger out and weekly stress-event) was associated with an increased mean average of BMI. For example, the mean difference in BMI increased by 41% for each 1 SD increase in cynical distrust (p<.01); and the mean difference in BMI increased by 45% for each 1 SD increase in global stress (p<.01). In fully-adjusted models, global perceived stress was associated with prevalent hypertension and diabetes (PR for hypertension: 1.07, 95%CI 1.00,1.07; PR for diabetes: 1.24, 95%CI 1.04, 1.47). Major life events were also associated with hypertension and diabetes. Each psychosocial measure (except cynicism and anger in) was associated with prevalent CVD. Conclusion: Efforts to reduce disparities in CVD may need to address environmental and psychosocial factors that place AA at higher risk.

Abstract MP007: Epicardial Fat Thickness: Distribution of and Associations With Cardiovascular Risk Factors in the Framingham Heart Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Michael L Chuang ◽  
Philimon Gona ◽  
Noriko Oyama-Manabe ◽  
Carol J Salton ◽  
Udo Hoffmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Cvd Risk Factors ◽  
Odds Ratios ◽  
Cvd Risk ◽  
Epicardial Fat Thickness ◽  
Heart Study ◽  
Fat Thickness ◽  
Fat Volume

Introduction: High pericardial fat volume (fatVOL) is associated with excess cardiovascular disease (CVD), but analyses for true fat volume can be time-consuming and require specialized software. Linear epicardial fat thickness (fatTHK) can be measured quickly from cardiac magnetic resonance (MRI) images and may serve as a surrogate for fatVOL. We sought to determine the distribution and CVD risk factor correlates of high fatTHK and to compare fatTHK with fatVOL in a community-dwelling adult cohort. Methods: Participants were drawn from the Framingham Heart Study Offspring cohort (N=995, aged 65±9 years, 54% women) and underwent cardiac MRI (SSFP sequence) and multidetector CT during 2002-2005. Clinical and risk factor covariates were obtained at the preceding cycle 7 examination (1998-2001). FatVOL was determined from volumetric MDCT data. FatTHK was measured from the MRI 4-chamber view over the midlevel right ventricular free wall at end-diastole. A healthy referent subsample (N=328), free of major CVD risk factors, was used to determine sex-specific cut points for high fatTHK. Odds ratios for high (>90th percentile) fatVOL and fatTHK versus common CVD risk factors were determined. Results: FatTHK was greater in men than women and increased with age in both sexes. FatTHK correlated with fatVOL at r=0.45 (p less than 0.001) High fatTHK was >=16.0 mm in men and >=13.3 mm in women, with 20.1% prevalence in men and 18.1 % in women. In both sexes, high fatVOL was associated ( Table ) with obesity, metabolic syndrome, dysglycemia, hypertension, prevalent CVD and hypertriglyceridemia. Similar associations, with slightly lower odds ratios, were seen for fatTHK. Conclusions: Greater fatTHK is associated with an excess burden of multiple CVD risk factors. Although correlation between linear fatTHK and true fatVOL was relatively modest, both measures appear to have similar associations with common CVD risk factors. FatTHK may be advantageous in that it can be determined quickly using standard MRI sequences for ventricular function. Table. Odds Ratios for High Pericardial Fat vs. Common CVD Risk Factors fatVOL: Men fatVOL: Women fatTHK: Men fatTHK: Women Obesity, BMI >=30 kg/m2 4.34 (2.78–6.78) 3.13 (2.03–4.82) 2.52 (1.77–3.60) 2.62 (1.84–3.74) Metabolic Syndrome 3.72 (2.38–5.83) 2.60 (1.65–4.08) 2.59 (1.75–3.84) 2.21 (1.53–3.17) Dysglycemia, FPG >=100 mg/dL 2.64 (1.72–4.06) 3.05 (1.98–4.68) 1.75 (1.22–2.50) 1.56 (1.10–2.23) Hypertension, S>=140 or D>=90 mmHg 2.51 (1.66–3.78) 1.96 (1.30–2.97) 2.10 (1.48–2.98) 1.58 (1.13–2.22) Prevalent CVD 1.94 (1.17–3.21) 2.48 (1.41–4.38) 1.73 (1.17–2.55) 1.83 (1.19–2.81) Triglycerides >=150 mg/dL 1.89 (1.25–2.86) 2.21 (1.43–3.42) 1.64 (1.15–2.34) 1.98 (1.38–2.82) Low HDL: M<40, W<50 mg/dL 1.57 (1.03–2.38) 1.44 (0.91–2.28) 1.40 (0.98–1.99) 2.57 (1.80–3.67)

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