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1.
J Thromb Haemost ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680443

RESUMO

BACKGROUND: Rare coding mutations underlying deficiencies of antithrombin and proteins C and S contribute to familial venous thromboembolism (VTE). It is uncertain whether rare variants play a role in the etiology of VTE in the general population. OBJECTIVES: We conducted a deep whole-exome sequencing (WES) study to investigate the associations between rare coding variants and the risk of VTE in two population-based prospective cohorts. PATIENTS/METHODS: WES was performed in the Longitudinal Investigation of Thromboembolism Etiology (LITE), which combines the ARIC study (316 incident VTE events among 3,159 African Americans (AAs) and 458 incident VTEs among 7,772 European Americans (EAs)) and the CHS study (60 incident VTEs among 1,751 EAs). We performed gene-based tests of rare variants (allele frequency <1%, exome-wide significance p<1.47x10-6 ) separately in each study and ancestry group, and meta-analyzed the results for the EAs in ARIC and CHS. RESULTS: In the meta-analysis of EAs, we identified one gene, PROC, in which the burden of rare, coding variants was significantly associated with increased risk of VTE (HR=5.42 [3.11, 9.42] for carriers versus non-carriers, p=2.27 x 10-9 ). In ARIC EAs, carriers of the PROC rare variants had on average 0.75 SD lower concentrations of plasma protein C and 0.28 SD higher D-dimer (p<0.05) than non-carriers. Adjustment for low protein C status did not eliminate the association of PROC burden with VTE. In AAs, rare coding PROC variants were not associated with VTE. CONCLUSIONS: Rare coding variants in PROC contribute to increased VTE risk in EAs in this general population sample.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31704668

RESUMO

BACKGROUND AND OBJECTIVES: apo L1 (APOL1) nephropathy risk alleles are associated with CKD in blacks. Although APOL1 has innate immune functions, little is known about the association of APOL1 genotypes with risk of infectious outcomes, such as sepsis. The objective of this study was to examine the associations of APOL1 nephropathy risk alleles with risk of sepsis in black adults. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We assessed the association of APOL1 risk alleles with incident sepsis in 10,366 black participants of the Reasons for Geographic and Racial Differences in Stroke study enrolled between 2003 and 2007 with follow-up through December 31, 2012. In Cox models adjusted for demographics, comorbid conditions, and principal components ancestry, we examined the association of APOL1 risk alleles with incident sepsis using recessive (comparing zero or one versus two risk alleles), dominant (zero versus one or two risk alleles), and additive genetic models. We also examined models stratified by diabetes and CKD status. RESULTS: A total of 1320 (13%) participants had two APOL1 risk alleles, 4719 (46%) had one risk allele, and 4327 (42%) participants had zero risk alleles. A total of 306 sepsis events occurred over a median 6.5 years (interquartile range, 4.5-8.1). There were no statistically significant associations of APOL1 genotype with sepsis risk under recessive genetic models. APOL1 genotypes were associated with sepsis risk under dominant (hazard ratio, 1.55; 95% confidence interval, 1.13 to 2.11) and additive (hazard ratio per variant allele copy, 1.25; 95% confidence interval, 1.02 to 1.53) genetic models adjusted for covariates and ancestry. These associations did not vary by diabetes or CKD status (P interaction>0.10 for both). CONCLUSIONS: In community-dwelling black adults, carriage of APOL1 nephropathy risk alleles are common and associated with higher risk of sepsis.

4.
Am J Cardiol ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31575423

RESUMO

The Pooled Cohort Equation (PCE) predicts 10-year risk of first-time atherosclerotic cardiovascular disease (ASCVD) events and was incorporated in analyses of a primary and secondary prevention population in the Systolic Blood Pressure Intervention Trial (SPRINT). Whether PCE enhances risk prediction among secondary prevention populations is unknown. We sought to compare ASCVD events by level of PCE-predicted risk among primary and secondary prevention SPRINT populations. SPRINT randomized adults with hypertension and ≥1 CVD risk factor or previous CVD events to systolic blood pressure control targeting <120 mm Hg or 135 to 139 mm Hg. We calculated the hazard ratio (HR) of ASCVD events among secondary versus primary (reference) prevention subgroups overall and by predicted 10-year ASCVD risk categories (<10%, 10% to <20%, 20% to <30%, and ≥30%) and within risk subgroups, comparing to the lowest risk category. Among 8,151 participants, 16% with previous CVD, mean age was 66 years and 35% were women. The HR for ASCVD events overall was 2.51 (1.96, 3.20). HR was 2.97 (1.47, 5.99) among <10% 10-year risk and 2.23 (1.38, 3.59) among ≥30% risk. Within subgroups comparing ≥30% to <10% risk (reference) categories, the HR was 2.85 (1.76, 4.63) for primary and 2.14 (1.07, 4.30) for the secondary prevention. In conclusion, history of previous events was a potent risk factor for subsequent ASCVD events. The PCE does not enhance risk prediction among secondary prevention populations and may differentially underestimate risk in secondary prevention populations with lowest predicted risk.

5.
Aging Clin Exp Res ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31630377

RESUMO

BACKGROUND AND AIM: Providing care to an older adult with a disability has been associated with increased risk to the caregiver's health, but most previous studies of caregiving and health compare persons who are already caregivers with poorly matched non-caregiving controls and are often based on convenience samples. In this report, we describe the enrollment of persons who transitioned into a family caregiving role while participating in a national epidemiological study. METHODS: Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were asked on two occasions 9-14 years apart if they were providing care on an ongoing basis to a family member with a chronic illness or disability. Those who answered "no" and "yes", respectively, to this caregiving question and reported sufficient caregiving responsibilities after their transitions were enrolled in the present study as incident caregivers (N = 251). Participants matched on multiple demographic and health history variables and who reported no history of caregiving were enrolled as non-caregiving controls (N = 251). RESULTS: Among eligible participants, 84% agreed to participate, and 47% of caregivers reported caring for a person with dementia. Descriptive analyses confirmed the success of the matching procedures for balancing the groups on multiple demographic and pre-caregiving health variables. Depressive symptoms and perceived stress increased significantly after the transition to caregiving. CONCLUSION: Comparable, population-based samples of incident caregivers and matched non-caregivers have been enrolled. Future analyses will examine within-person changes in health and circulating biomarkers as a function of the transition to caregiving.

6.
Am J Kidney Dis ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31563468

RESUMO

RATIONALE & OBJECTIVE: APOL1 nephropathy risk alleles are associated with the development of chronic kidney disease (CKD) in African Americans. Although CKD is an established risk factor for mortality, associations of APOL1 risk alleles with mortality are uncertain. STUDY DESIGN: Prospective cohort. SETTINGS & PARTICIPANTS: 10,380 African American and 17,485 white American participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. EXPOSURES: APOL1 nephropathy risk alleles. OUTCOMES: All-cause and cause-specific mortality. ANALYTICAL APPROACH: Cox proportional hazards models were used to examine the association of APOL1 high-risk genotypes (2 risk alleles) versus APOL1 low-risk genotypes (0/1 risk allele) with all-cause and cause-specific mortality in African Americans and examine the risk for all-cause mortality in African Americans with high-risk genotypes versus African Americans with low-risk genotypes and white Americans. RESULTS: APOL1 high-risk participants were younger and had a higher prevalence of albuminuria than low-risk participants. There was no statistically significant association of APOL1 high- versus low-risk genotypes with all-cause mortality in models adjusted for sociodemographic variables, comorbid conditions, and kidney function (HR, 0.88; 95% CI, 0.77-1.01). After further adjustment for genetic ancestry in a subset with available data, a statistically significant association emerged (HR, 0.81; 95% CI, 0.69-0.96). Associations differed by CKD status (Pinteraction=0.04), with African Americans with high-risk genotypes having lower risk for mortality than those with low-risk genotypes in fully adjusted models (HR, 0.78; 95% CI, 0.62-0.99) among those with CKD, but not those without CKD (HR, 0.84; 95% CI, 0.66-1.05). Compared with white Americans, African Americans with high-risk genotypes had a similar rate of mortality, whereas African Americans with low-risk genotypes had a higher rate of mortality (HR, 1.07; 95% CI, 1.00-1.14) in fully adjusted models. LIMITATIONS: Lack of follow-up measures of kidney function. CONCLUSIONS: African Americans with high-risk APOL1 genotypes had lower mortality than those with low-risk genotypes in multivariable-adjusted models including genetic ancestry.

7.
J Lipid Res ; 60(11): 1946-1952, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31511398

RESUMO

The pharmacologic inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) lowers lipoprotein (a) [Lp(a)] concentrations. However, the impact of genetic PCSK9 loss-of-function variants (LOFVs) on Lp(a) is uncertain. We determined the association of PCSK9 LOFVs with Lp(a) measures among black adults. Genotyping for PCSK9 LOFVs was conducted in 10,196 black Reasons for Geographic and Racial Differences in Stroke study participants. Among 241 participants with and 723 randomly selected participants without PCSK9 LOFVs, Lp(a) concentations, apo(a) kringle IV (KIV) repeats (a proxy for isoform size), and oxidized phospholipid (OxPL) apoB levels were measured using validated methods. Median Lp(a) concentrations among participants with and without PCSK9 LOFVs were 63.2 and 80.4 nmol/l, respectively (P = 0.016). After adjusting for age, sex, estimated glomerular filtration rate, LDL cholesterol, and statin use, participants with versus without a PCSK9 LOFV had a lower median Lp(a) concentration [Δ = -18.8 nmol/l (95% CI: -34.2, -3.3)]. Median apo(a) isoform sizes were 24 and 23 KIV repeats (P = 0.12) among participants with and without PCSK9 LOFVs, respectively [Δ = 1.1 (95% CI: 0.2, 2.0) after adjustment]. Median OxPL-apoB levels among participants with and without PCSK9 LOFVs were 3.4 and 4.1 nM (P = 0.20), respectively [Δ = -1.2 nM (95% CI -2.4, -0.04) after adjustment]. Among black adults, PCSK9 LOFVs were associated with lower Lp(a) concentration and OxPL-apoB levels.

8.
Thromb Res ; 182: 89-94, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473403

RESUMO

INTRODUCTION: High molecular weight kininogen (HK) and prekallikrein (PK) are proteins in the kallikrein/kinin system of the coagulation cascade. They play an important role in the contact activation system of the intrinsic coagulation pathway, renin-angiotensin activation, and inflammation. Hence these proteins have been posited to affect the occurrence of cardiovascular events and thus to be potential therapeutic targets. Previous case-control studies have provided inconsistent evidence for an association of HK and PK with cardiovascular disease. METHODS: In the prospective population-based Atherosclerosis Risk in Communities(ARIC) Study, we used Cox proportional hazards regression models to investigate the association in 4195 middle-aged adults of plasma HK and PK concentrations in 1993-95 (linearly and in quartiles) with incident coronary heart disease, ischemic stroke, and heart failure through 2016. RESULTS: Over a mean of 18 years follow-up, we identified incident cardiovascular events (coronary heart disease and ischemic stroke) in 618 participants and heart failure in 667. We observed no significant relation between HK or PK and cardiovascular disease or heart failure, before and after adjusting for several potential confounding variables. CONCLUSIONS: We found no compelling evidence to support an association of plasma HK or PK concentrations with incident CHD, ischemic stroke, or heart failure.

9.
Am Heart J ; 217: 94-100, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31520899

RESUMO

BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker used in vascular risk prediction, though with less data in people of color. Blacks have higher stroke incidence and also higher CRP than whites. We studied the association of CRP with ischemic stroke risk in blacks and whites. METHODS: REGARDS, an observational cohort study, recruited and followed 30,239 black and white Americans 45 years and older for ischemic stroke. We calculated hazard ratios and 95% CIs of ischemic stroke by CRP category (<1, 1-3, 3-10, and ≥10 mg/L) adjusted for age, sex and stroke risk factors. RESULTS: There were 292 incident ischemic strokes among blacks and 439 in whites over 6.9 years of follow-up. In whites, the risk was elevated for CRP in the range from 3 to 10 mg/L and even higher for CRP >10 mg/L, whereas in blacks, an association was only seen for CRP >10 mg/L. Considered as a continuous variable, the risk factor-adjusted hazard ratios per SD higher lnCRP were 1.18 (95% CI 1.09-1.28) overall, 1.14 (95% CI 1.00-1.29) in blacks, and 1.22 (95% CI 1.10-1.35) in whites. Spline regression analysis visually confirmed the race difference in the association. CONCLUSIONS: CRP may not be equally useful in stroke risk assessment in blacks and whites. Confirmation, similar study for coronary heart disease, and identification of reasons for these racial differences require further study.

10.
J Thromb Haemost ; 2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31423717

RESUMO

BACKGROUND: The Khorana Score is a validated risk score for predicting 6-month incidence of cancer-associated venous thromboembolism (CAT) among patients starting chemotherapy. Venous thromboembolism (VTE) risk factors important in the general population, including age, sex, prior VTE, and hospitalization, are not included in this score, their association with VTE in cancer patients is unknown. OBJECTIVE: To examine risk factors for CAT and the impact of incorporating longitudinal hospitalization into risk assessment. METHODS: Risk factors were recorded among patients starting chemotherapy at a single institution from 2012-14. Hospitalization and time-periods after hospitalization were assessed as time-varying covariates. Logistic regression was used to determine factors related to 6-month CAT risk (the Khorana Score endpoint). Proportional hazard models were used for risk factor identification throughout the 3-year observation period. RESULTS: Among 1,583 patients starting chemotherapy (mean age 60, 48% male), 187 developed CAT (11.8%) with 129 (69%) cases occurring within 6 months of starting chemotherapy. In the 6-month analysis, no additional risk factors were associated with CAT. In the 3-year analysis, male sex (HR 1.57, 95%CI 1.21, 2.07), prior VTE (HR 2.12, 95%CI 1.41, 3.18), and hospitalization (HR 2.69, 95%CI 1.92, 3.75) were associated with increased hazard of CAT, adjusting for risk factors in the Khorana score. CONCLUSIONS: When time-to-event data were incorporated into CAT risk assessment, male sex, prior VTE, and hospitalization were important risk factors. These data highlight the need to consider dynamic methods for assessing VTE risk in cancer patients, with particular attention to the period around hospitalizations.

11.
J Am Soc Nephrol ; 30(10): 2027-2036, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31383730

RESUMO

BACKGROUND: Two coding variants in the apo L1 gene (APOL1) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. METHODS: We conducted a two-stage individual participant data meta-analysis to assess the association of APOL1 kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts. RESULTS: Over 8.9±5.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two APOL1 kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by APOL1 genotype. APOL1 genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index. CONCLUSIONS: In this large, two-stage individual participant data meta-analysis, APOL1 kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures.

12.
BMJ ; 366: l4363, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340984

RESUMO

OBJECTIVES: To determine the rate of a first recurrent venous thromboembolism (VTE) event after discontinuation of anticoagulant treatment in patients with a first episode of unprovoked VTE, and the cumulative incidence for recurrent VTE up to 10 years. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, and the Cochrane Central Register of Controlled Trials (from inception to 15 March 2019). STUDY SELECTION: Randomised controlled trials and prospective cohort studies reporting symptomatic recurrent VTE after discontinuation of anticoagulant treatment in patients with a first unprovoked VTE event who had completed at least three months of treatment. DATA EXTRACTION AND SYNTHESIS: Two investigators independently screened studies, extracted data, and appraised risk of bias. Data clarifications were sought from authors of eligible studies. Recurrent VTE events and person years of follow-up after discontinuation of anticoagulant treatment were used to calculate rates for individual studies, and data were pooled using random effects meta-analysis. Sex and site of initial VTE were investigated as potential sources of between study heterogeneity. RESULTS: 18 studies involving 7515 patients were included in the analysis. The pooled rate of recurrent VTE per 100 person years after discontinuation of anticoagulant treatment was 10.3 events (95% confidence interval 8.6 to 12.1) in the first year, 6.3 (5.1 to 7.7) in the second year, 3.8 events/year (95% confidence interval 3.2 to 4.5) in years 3-5, and 3.1 events/year (1.7 to 4.9) in years 6-10. The cumulative incidence for recurrent VTE was 16% (95% confidence interval 13% to 19%) at 2 years, 25% (21% to 29%) at 5 years, and 36% (28% to 45%) at 10 years. The pooled rate of recurrent VTE per 100 person years in the first year was 11.9 events (9.6 to 14.4) for men and 8.9 events (6.8 to 11.3) for women, with a cumulative incidence for recurrent VTE of 41% (28% to 56%) and 29% (20% to 38%), respectively, at 10 years. Compared to patients with isolated pulmonary embolism, the rate of recurrent VTE was higher in patients with proximal deep vein thrombosis (rate ratio 1.4, 95% confidence interval 1.1 to 1.7) and in patients with pulmonary embolism plus deep vein thrombosis (1.5, 1.1 to 1.9). In patients with distal deep vein thrombosis, the pooled rate of recurrent VTE per 100 person years was 1.9 events (95% confidence interval 0.5 to 4.3) in the first year after anticoagulation had stopped. The case fatality rate for recurrent VTE was 4% (95% confidence interval 2% to 6%). CONCLUSIONS: In patients with a first episode of unprovoked VTE who completed at least three months of anticoagulant treatment, the risk of recurrent VTE was 10% in the first year after treatment, 16% at two years, 25% at five years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death. These estimates should inform clinical practice guidelines, enhance confidence in counselling patients of their prognosis, and help guide decision making about long term management of unprovoked VTE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017056309.


Assuntos
Anticoagulantes/uso terapêutico , Medição de Risco/métodos , Tromboembolia Venosa , Suspensão de Tratamento , Humanos , Recidiva , Tempo , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/fisiopatologia
13.
JCI Insight ; 52019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31162140

RESUMO

BACKGROUND: Black individuals have lower natriuretic peptide levels and greater risk of heart failure (HF) than white individuals. Higher N-terminal-pro-B-type natriuretic peptide (NT-proBNP) is associated with increased risk of incident HF, but little information is available in black individuals. We examined race-specific differences in 1) the association of NT-proBNP with incident HF and 2) the predictive ability of NT-proBNP for incident HF across body mass index (BMI) and estimated glomerular filtration rate (eGFR) categories. METHODS: In a prospective case-cohort study, baseline NT-proBNP was measured among 687 participants with incident HF and 2,923 (weighted 20,075) non-case randomly selected participants. Multivariable Cox proportional hazard modeling was used to assess the objectives of our study. Global Wald Chi-square score estimated from multivariable Cox models was used to assess predictive ability of NT-proBNP across BMI and eGFR categories. RESULTS: In the multivariable model, a doubling of NT-proBNP concentration was associated with greater risk of incident HF among white individuals [hazard ratio (HR): 1.73; 95% CI: 1.55-1.94] than black individuals (HR: 1.51; 95% CI: 1.34-1.70); Pinteraction by race = 0.024. Higher NT-proBNP was the strongest predictor of incident HF across all BMI and eGFR categories among white individuals. By contrast, among black individuals with obesity (BMI ≥ 30 kg/m2) or eGFR < 60 mL/min/1.73 m2, the predictive ability of NT-proBNP for incident HF was attenuated. CONCLUSIONS: The magnitude of the association of higher NT-proBNP with incident HF risk was greater among white individuals than black individuals. The diminished ability of NT-proBNP to predict the risk of HF in black population with obesity or impaired kidney function highlights the need of further investigations.

14.
15.
JACC Heart Fail ; 7(5): 394-401, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31047019

RESUMO

OBJECTIVES: This study examined the association between urinary albumin excretion and incident heart failure (HF) hospitalization. BACKGROUND: Excess urinary albumin excretion is more strongly associated with incident stroke and coronary heart disease risk in black than in white individuals. Whether similar associations extend to HF is unclear. METHODS: This study examined the associations between the urinary albumin-to-creatinine ratio (ACR) and incident hospitalization for HF overall in 24,433 REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants free of suspected HF at baseline; findings were stratified by race and HF subtype (preserved vs. reduced ejection fraction). Models were adjusted for sociodemographic, clinical, and laboratory variables including estimated glomerular filtration rate, and multiple imputation was used to account for missing covariate data. RESULTS: After a median follow-up of 9.2 years, 881 incident HF events (332 preserved ejection fraction, 447 reduced ejection fraction, 102 unspecified) were observed. Compared to the lowest ACR category (<10 mg/g), the risk of incident HF increased with increasing ACR categories (10 to 29 mg/g hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.26 to 1.78; 30 to 300 mg/g HR: 2.32; 95% CI: 1.93 to 2.78; >300 mg/g HR: 4.42; 95% CI: 3.36 to 5.83) in the fully adjusted model. Results did not differ by race. The magnitude of the association between ACR and HF with preserved ejection fraction was greater than with HF with reduced ejection fraction (HR comparing highest vs. lowest ACR category: 6.20; 95% CI: 4.15 to 9.26 vs. HR: 4.37; 95% CI: 3.00 to 6.25, respectively; p = 0.05). CONCLUSIONS: Higher ACR was associated with greater risk of incident HF hospitalization in community-dwelling black and white adults.

16.
BMJ Open ; 9(5): e027175, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31079085

RESUMO

OBJECTIVES: While awareness of cigarette smoking's harmful effects has increased, determinants associated with smoking status remain understudied, including potential racial differences. We aim to examine factors associated with former versus current smoking status and assess whether these associations differed by race. SETTING: We performed a cross-sectional analysis using the population-based Reasons for Geographic and Racial Differences in Stroke(REGARDS)study. OUTCOME MEASURES: Logistic regression was used to calculate the OR of former smoking status compared with current smoking status with risk factors of interest. Race interactions were tested using multiplicative interaction terms. RESULTS: 16 463 participants reported smoking at least 100 cigarettes in their lifetime. Seventy-three per cent (n=12 067) self-reported former-smoker status. Physical activity (reference (REF) <3×/week; >3×/week: OR=1.26, 95% CI 1.11 to 1.43), adherence to Mediterranean diet (REF: low; medium: OR=1.46, 95% CI 1.27 to 1.67; high: OR=2.20, 95% CI 1.84 to 2.64), daily television viewing time (REF: >4 hours; <1 hour: OR=1.32, 95% CI 1.10 to 1.60) and abstinence from alcohol use (REF: heavy; none: OR=1.50, 95% CI 1.18 to 1.91) were associated with former-smoker status. Male sex, higher education and income $35 000-$74 000 (REF: <$20 000) were also associated with former-smoker status. Factors associated with lower odds of reporting former-smoker status were younger age (REF: ≥65 years; 45-64 years: OR=0.34, 95% CI 0.29 to 0.39), black race (OR=0.62, 95% CI 0.53 to 0.72) and single marital status (REF: married status; OR=0.66, 95% CI 0.51 to 0.87), being divorced (OR=0.60, 95% CI 0.50 to 0.72) or widowed (OR=0.70, 95% CI 0.57 to 0.85). Significant interactions were observed between race and alcohol use and dyslipidaemia, such that black participants had higher odds of reporting former-smoker status if they were abstinent from alcohol (OR=2.32, 95% CI 1.47 to 3.68) or had a history of dyslipidaemia (OR=1.31, 95% CI 1.06 to 1.62), whereas these relationships were not statistically significant in white participants. CONCLUSION: Efforts to promote tobacco cessation should consist of targeted behavioural interventions that incorporate racial differences.

17.
Neurology ; 92(20): e2375-e2384, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31004072

RESUMO

OBJECTIVE: We studied circulating interleukin (IL)-6, IL-8, and IL-10 concentrations and incident ischemic stroke risk in a biracial cohort, and determined if these cytokines mediated the racial disparity in stroke incidence affecting the black population. METHODS: The Reasons for Geographic and Racial Differences in Stroke study enrolled 30,237 black and white men and women age ≥45 in 2003-2007. We measured baseline IL-6, IL-8, and IL-10 in a case-cohort study of 557 participants with incident stroke over 5.4 years and 951 participants in a cohort sample. RESULTS: IL-6, but not IL-8 or IL-10, was higher in cases compared to the cohort sample (mean 4.5 vs 3.7 ng/mL; p < 0.001). Only IL-6 was associated with stroke risk factors. Adjusting for age, sex, and race, the hazard ratio (HR; 95% confidence interval) for incident stroke for the highest vs lowest quartile of IL-6 was 2.4 (1.6-3.4). HRs for the highest vs lowest quartiles of IL-8 and IL-10 were 1.5 (1.0-2.1) and 1.4 (1.0-1.9), respectively. After additional adjustment for stroke risk factors, only higher IL-6 remained associated with stroke risk (HR 2.0; 1.2-3.1). Associations did not differ by race. Mediation analyses showed that IL-6 mediated the black-white disparity in stroke risk, but mediation was via IL-6 associations with stroke risk factors. CONCLUSIONS: In this biracial population-based sample, IL-6 was strongly associated with risk of incident stroke and mediated the racial disparity in stroke via inflammatory effects of risk factors. Further study on the clinical utility of IL-6 measurement in stroke risk assessment would be helpful.

18.
J Electrocardiol ; 55: 1-5, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028976

RESUMO

BACKGROUND: Sickle cell trait (SCT), sickle cell disease's (SCD) carrier status, has been recently associated with worse cardiovascular and renal outcomes. An increased prevalence of atrial fibrillation (AF) is documented in SCD patients; however, studies in individuals with SCT are lacking. OBJECTIVES: To determine the association of SCT with AF. METHODS: Among African-American participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study we assessed the association of SCT (by ECG or medical history) with prevalent AF using logistic regression adjusting for age, sex, income, education, history of stroke, myocardial infarction, diabetes, hypertension, and chronic kidney disease. A second evaluation was performed a mean of 9.2 years later among available participants, and the same model was used to test the association of SCT with incident AF. RESULTS: In 10,409 participants with baseline ECG data and genotyping, 778 (7.5%) had SCT and 811 (7.8%) had prevalent AF. After adjusting for age, sex, education and income, SCT was associated with AF, OR 1.32 (95% CI 1.03-1.70). The association with incident AF assessed at the second in-home visit with the same adjustments was similar; OR 1.25 (95% CI 0.77-2.03). CONCLUSIONS: SCT was associated with a higher prevalence of AF and a non-significantly higher incident AF over a 9.2 year period independent of AF risk factors. SCT remained associated with prevalent AF after adjusting for potential factors on the causal pathway such as hypertension and chronic kidney disease suggesting alternate mechanisms for the increased risk.

19.
Am J Med ; 132(8): 970-976, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30953632

RESUMO

INTRODUCTION: Venous thromboembolism incidence rates are 30%-100% higher in US blacks than whites. We examined the degree to which differences in the frequencies of socioeconomic, lifestyle, medical risk factors, and genetic variants explain the excess venous thromboembolism risk in blacks and whether some risk factors are more strongly associated with venous thromboembolism in blacks compared with whites. METHODS: We measured venous thromboembolism risk factors in black and white participants of the Atherosclerosis Risk in Communities study in 1987-1989 and followed them prospectively through 2015 for venous thromboembolism incidence. RESULTS: Over a mean of 22 years, we identified 332 venous thromboembolisms in blacks and 578 in whites, yielding 65% higher crude incidence rates per 1000 person-years in blacks. The age and sex-adjusted hazard ratio (95% confidence interval) of venous thromboembolism for blacks compared with whites was 2.04 (1.76, 2.37) for follow-up >10 years and was attenuated to 1.14 (0.89, 1.46) when adjusted for baseline confounders or mediators of the race association, which tended to be more common in blacks. For example, adjustment for just baseline weight, family income, and concentration of plasma factor VIII reduced the regression coefficient for race by 75%. There were no significant (P <0.05) 2-way multiplicative interactions of race with any risk factor, except with a 5-single nucleotide polymorphism (5-SNP) genetic risk score (a weaker venous thromboembolism risk factor in blacks) and with hospitalization for heart failure (a stronger venous thromboembolism risk factor in blacks). CONCLUSION: The higher incidence rate of venous thromboembolism in blacks than whites was mostly explained by blacks having higher frequencies of venous thromboembolism risk factors.

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