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  • 1
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 141, No. Suppl_1 ( 2020-03-03)
    Abstract: Background: Dietary habits are a major determinant of cardiovascular disease (CVD) and mortality risk. However, data on the role of dairy intake on the risk of CVD and death has been inconsistent. Objective: The primary objective is to assess whether total consumption of dairy products is associated with a lower risk of CVD and/or total mortality among US Veterans. Methods: In a prospective cohort study of US Veterans from the Million Veteran Program (MVP), dairy intake was collected through a self-reported food frequency questionnaire at baseline. Incidence of composite CVD (including MI, stroke, and cardiovascular death) and total mortality were measured via electronic health records and the National Death Index database. Cox Proportional hazard models were used to compute the multivariable adjusted hazard ratio of CVD and total mortality. Results: A total of 188,833 Veterans were studied with a mean age of 63.3 ± 12.3 years. After a mean follow-up of 3.2 years for CVD and 3.3 years for total mortality, 9,898 cases of CVD and 6,826 deaths occurred. Median dairy consumption was 1.2 servings/day. In a multivariable Cox regression adjusted for age, gender, race, body mass index (BMI), smoking, alcohol use, exercise, diet quality, diabetes mellitus, and level of education; hazard ratios (95% CI) for CVD were 1.00 (0.89-1.14) for dairy intake of 1-2 servings/week, 1.05 (0.92-1.20) for 2-3 servings/week, 1.01 (0.90-1.12) for 3-5 servings/week, 0.97 (0.87-1.08) for 5-7 servings/week, 0.96 (0.87-1.05) for 1-2 servings/day, 1.02 (0.91-1.13) for 2-3 servings/day, 1.02 (0.90-1.15) for 3-4 servings/day, and 1.11 (0.98-1.26) for 4+ servings/day as compared to 〈 1 serving/week. For total mortality, the hazard ratios across consecutive categories of dairy intake were 0.85 (0.73-0.99), 0.83 (0.70-0.99), 0.87 (0.76-0.99), 0.84 (0.74-0.96), 0.94 (0.84-1.06), 1.10 (0.97-1.25), 1.12 (1.04-1.39), and 1.36 (1.18-1.58). Conclusion: Dairy intake was not associated with composite CVD. However, there was suggestive evidence for J-shaped relation of dairy intake with total mortality.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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  • 2
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 141, No. Suppl_1 ( 2020-03-03)
    Abstract: Background: While observational data suggest a higher risk of coronary artery disease with frequent egg consumption, only limited and inconsistent data are available on the relation of egg consumption with stroke. Objective: To test the hypothesis that egg consumption is positively associated with the incidence of ischemic stroke among Veterans. Methods: The Million Veteran Program is an ongoing observational study designed to study genetic determinants of chronic diseases among Veterans (2011 to now). Egg consumption was self-reported at baseline using validated Willett food questionnaires. We used ICD 9 codes 433, 434, 436, 437.0, and 437.6 and ICD 10 codes I63, I65, I66, I67.2, I67.6 and I67.8 to identify ischemic stroke using previously validated algorithm and multivariable Cox proportional hazard model to estimate relative risks. Results: A total of 234,032 Veterans provided data on egg consumption and were free of stroke at baseline. Mean age at baseline was 65.6 (SD: 11.7) years and 91.6% (214,373 of 234,032) were men. Median egg consumption was 2-4 eggs per week. During a mean follow up of 3.2 years, a total of 5,747 new cases of fatal or non-fatal acute ischemic stroke occurred. Crude incidence rates for acute ischemic stroke were 6.5, 7.2, 7.1, 7.4, 8.0, and 8.3 cases per 1000 person-years for egg consumption of 〈 1/month, 1-3/month, 1/week, 2-4/week, 5-6/week, and ≥ 1/day, respectively. Corresponding adjusted hazard ratios (95% CI) were 1.00 (ref), 1.10 (0.97-1.25), 1.10 (0.97-1.25), 1.13 (1.00 -1.27), 1.19 (1.04-1.37), and 1.25 (1.09-1.44) controlling for age, sex, ethnicity, body mass index, education, smoking, alcohol intake, and overall diet quality (p linear trend 0.0007). The egg-stroke relation was not modified by body mass index, sex, or diabetes status. Conclusion: Egg consumption is positively associated with incidence of acute ischemic stroke among Veterans.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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  • 3
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 141, No. Suppl_1 ( 2020-03-03)
    Abstract: Introduction: Obesity and metabolic dysfunction, individually, are known risk factors of stroke, coronary artery disease (CAD), and mortality. However, few studies have examined the long-term risk for CAD among non-obese people with metabolic dysfunction, and no studies have been conducted for Veterans of the United States. Hypothesis: Veterans who are metabolically obese normal weight (MONW) at baseline have an increased risk of developing CAD compared to metabolically healthy normal weight (MHNW) veterans enrolled in the Million Veteran Program (MVP). Methods: We included MVP participants who had a stable normal body mass index (18.5-25kg/m 2 ) five years prior to enrollment. Metabolic obesity was defined as having three or more of the Adult Treatment Panel III criteria [diabetes, hypertension, low HDL-C (≤40 mg/dl for men, ≤50 mg/dl for women), and high triglycerides (≥150 mg/dl)] at enrollment. CAD was defined as non-fatal myocardial infarction, ischemic heart disease or angina pectoris. Participants with prevalent CAD, major cancer s and incomplete lifestyle information were excluded. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CAD incidence. In secondary analyses, we stratified by sex and race to evaluate possible effect modification. Results: Of the 16,764 people identified as normal weight with complete data, 15% were MONW, 84.5% were male, 84.4% were White and the mean age was 63.1 ± 14.2. Over a median follow up of 3.6 (IQR 1.8-5.2) years, there were 847 incident CAD events observed. MONW individuals had a 64% (95% CI: 40 -91%) higher risk of CAD compared to normal weight individuals, controlling for age, race, sex, education, smoking status, physical activity, alcohol use and diet. In secondary analyses, we observed a nominally higher risk among women who were MONW [HR (95% CI): 2.74 (1.30-5.77) for women vs. 1.60 (1.37-1.88) for men], however the interaction of MONW and sex was not statistically significant (interaction p=0.19). Similarly, the interaction of MONW and race was not statistically significant [1.62 (1.37-1.92) for White, 1.55 (0.97-2.48) for Black, and 2.26 (1.03-4.95) for other, interaction p=0.83)] . Conclusions: MONW Veterans had a higher risk of CAD compared to MHNW Veterans. This risk was magnified in female Veterans and attenuated in White and Black Veterans compared to other races (Asian, Pacific Islander, Native American, other). These findings will need to be validated in future studies.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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  • 4
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 141, No. Suppl_1 ( 2020-03-03)
    Abstract: Introduction: Moderate alcohol consumption has been associated with lower risk of acute ischemic stroke (AIS) in the general population, but this relation has not been examined among U.S. Veterans. Furthermore, inconsistent data are available on the relation of alcohol and all-cause mortality. Methods: Million Veteran Program (MVP) participants who completed a lifestyle survey were eligible for analysis (n=335,754). We combined grams of ethanol in wine, beer, and spirits from the food frequency questionnaire to estimate grams/day (g/d). Participants were categorized into categories of: Never, former, or current drinkers of ≤6 g/d, 〉 6-12 g/d, 〉 12-24 g/d, 〉 24-36 g/d, 〉 36-48 g/d, and 〉 48 g/d. We defined incident AIS as 1 inpatient or 2 outpatient codes (ICD-9 433-434.XX, 436.XX, 437.0, 437.6; ICD-10 codes I63.XX, I65-I66.XX, I67.2, I67.6, I67.8) using the VA electronic health record. Participants with prevalent CVD (n=93,496), missing alcohol data (n=24,871), no follow-up time (n=18,948) or missing age or sex (n=135) were excluded. We used a Cox Proportional Hazards model to relate alcohol consumption and AIS and mortality (separately) adjusting for age, sex, race, body mass index, smoking, education, exercise, DASH score, diabetes, and hypertension status. A sensitivity analysis using simulation reclassifying never drinkers with prevalent comorbidities assessed the impact of potential exposure misclassification on effect estimates. Results: Among 198,304 participants, the mean age was 64y (SD=12), and 10% were women. During a mean follow up of 3.3 years, 3,834 AIS and 7,020 deaths occurred. Using never drinkers as the reference group, we identified a 20-26% (95% CI range: 0.42-0.93) lower risk of AIS, and a 29-39% (95% CI range: 0.46-0.80) lower risk of mortality among drinkers of 〉 0-36 g/d, respectively (Figure 1). In sensitivity analyses, HRs were attenuated but the effects remained robust. Conclusion: Our data show a lower risk of AIS and all-cause mortality with moderate alcohol consumption among MVP participants.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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  • 5
    In: Journal of Traumatic Stress, Wiley, Vol. 32, No. 2 ( 2019-04), p. 226-237
    Abstract: Traditional and Simplified Chinese Abstracts by the Asian Society for Traumatic Stress Studies (AsianSTSS) 簡體及繁體中文撮要由亞洲創傷心理研究學會翻譯 Validation of an Electronic Medical Record‐Based Algorithm for Identifying Posttraumatic Stress Disorder in U.S. Veterans Traditional Chinese 標題: 用以找出患創傷後壓力症美國退役軍人的電子健康紀錄為本演算法的效度驗證 撮要: 我們採用美國退伍軍人事務部(VA)電子健康紀錄(EMR)系統, 建立用以找出曾患創傷後壓力症(PTSD)的美國退役軍人的演算法。我們有見針對退役軍人患PTSD的基因組關連研究需有一個有效的EMR為本表型, 以找出數以千計的個案和對照, 因而作此研究。我們以人手進行圖表回顧作為黃金標準 (n = 500)。在演算法和圖表回顧中的分類法都有三種有可能:很大機會患PTSD、有可能患PTSD、 很大機會沒有患PTSD。我們採用Lasso迴歸法並進行交叉驗證, 從EMR選取具統計顯著性的PTSD預測變量, 然後對每個研究樣本作出患PTSD的概率分數預測(值域: 0–1.00)。我們採用的概率分析法(Lasso 演算法) 相比規條為本的分析法 (國際疾病分類 [ICD] 演算法), 在圖表回顧方面反映稍為較高的整體吻合百分比 (80% vs. 75%), 並有較高敏感度(0.95 vs. 0.84)和準確度(AUC = 0.95 vs. 0.90)。針對Lasso的分析結果, 我們以0.7概率作為取錄點以最後定義VA人口的PTSD個案對照狀態。圖表回顧對於PTSD 分類 (把有可能患 PTSD 及很大機會沒患PTSD結合 ) , 最後的演算法敏感度為 0.99、特殊度 0.99、正向預測值 0.95、負向預測值1.00。此演算法對VA的其他研究和非量化改善計劃可能有所幫助。 Simplified Chinese 标题: 用以找出患创伤后压力症美国退役军人的电子健康纪录为本算法的效度验证 撮要: 我们采用美国退伍军人事务部(VA)电子健康纪录(EMR)系统, 建立用以找出曾患创伤后压力症(PTSD)的美国退役军人的算法。我们有见针对退役军人患PTSD的基因组关连研究需有一个有效的EMR为本表型, 以找出数以千计的个案和对照, 因而作此研究。我们以人手进行图表回顾作为黄金标准 (n = 500)。在算法和图表回顾中的分类法都有三种有可能:很大机会患PTSD、有可能患PTSD、 很大机会没有患PTSD。我们采用Lasso回归法并进行交叉验证, 从EMR选取具统计显著性的PTSD预测变量, 然后对每个研究样本作出患PTSD的概率分数预测(值域: 0–1.00)。我们采用的概率分析法(Lasso 算法) 相比规条为本的分析法 (国际疾病分类 [ICD] 算法), 在图表回顾方面反映稍为较高的整体吻合百分比 (80% vs. 75%), 并有较高敏感度(0.95 vs. 0.84)和准确度(AUC = 0.95 vs. 0.90)。针对Lasso的分析结果, 我们以0.7概率作为取录点以最后定义VA人口的PTSD个案对照状态。图表回顾对于PTSD 分类 (把有可能患 PTSD 及很大机会没患PTSD结合 ) , 最后的算法敏感度为 0.99、特殊度 0.99、正向预测值 0.95、负向预测值1.00。此算法对VA的其他研究和非量化改善计划可能有所帮助。
    Type of Medium: Online Resource
    ISSN: 0894-9867 , 1573-6598
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2017312-X
    SSG: 2,1
    SSG: 5,2
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  • 6
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 137, No. suppl_1 ( 2018-03-20)
    Abstract: Introduction: Many studies have shown an inverse association of omega-3 polyunsaturated fatty acid (PUFA) from fish intake and supplementation with coronary heart disease (CHD) mortality. However, findings on the relationship of omega-3 PUFA with nonfatal CHD and stroke are less consistent. Higher doses or prolonged intake may be needed to affect non-fatal cardiovascular events. We hypothesized that among Veterans, greater baseline fish intake is associated with a lower risk of nonfatal CHD and stroke, particularly among those who regularly use omega-3 supplements. Methods: The Million Veteran Program (MVP) is an ongoing nation-wide longitudinal cohort study of U.S. Veterans with self-reported survey, biospecimen, and electronic health record data. Participants who were free of CHD or stroke at the time of the baseline food frequency questionnaire were included in this analysis. Separate Cox proportional hazard models were used to assess the associations of fish intake with non-fatal incident CHD and stroke, defined from electronic health records using validated algorithms. Fish intake (serving=3-5 oz.) within the past year was categorized as 〈 1 serving/month, 1-3 servings/month, 1 serving/week, 2-4 servings/week, 5-6 servings/week, and 1+ serving/day. We assessed whether omega-3 fatty acid supplementation (yes/no) modifies these relationships by testing its interaction with fish intake. Multivariable models included demographics and known CHD and stroke risk factors: age, sex, race, smoking status, alcohol use, physical activity, education, overall dietary pattern, BMI, family history of CHD or stroke, and baseline diabetes, hypertension, and use of statins and fibrates. Results: Among 508,699 MVP participants to date, 210,180 (mean age 66±12 years, 92.1% male) were free of CHD or stroke and had data from the food frequency questionnaire at baseline. Median fish intake was 1 serving/week and 21.7% (45,552 out of 210,180) regularly took omega-3 supplements. Over a median follow-up of 2.9 years, there were 5,991 and 4,244 incident cases of non-fatal CHD and stroke, respectively. Using 〈 1 fish serving/month as the reference, multivariable adjusted HR (95% CI) for CHD were 0.99 (0.91-1.07) for 1-3 servings/month, 1.06 (0.98-1.15) for 1 serving/week, 1.06 (0.96-1.16) for 2-4 servings/week, 1.26 (1.03-1.53) for 5-6 servings/week, and 0.96 (0.68-1.34) for 1+ serving/day, (p-trend=0.08); corresponding values for stroke were 0.95 (0.87-1.05) for 1-3 servings/month, 0.96 (0.87-1.06) for 1 serving/week, 0.99 (0.88-1.11) for 2-4 servings/week, 1.05 (0.83-1.34) for 5-6 servings/week, and 1.23 (0.87-1.74) for 1+ serving/day, (p-trend=0.60). Intake of omega-3 fatty acid supplements did not modify the fish-CHD/stoke relations (p-interaction=0.32 and 0.82, respectively). Conclusions: We observed no consistent association between fish intake and non-fatal CHD or stroke.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1466401-X
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  • 7
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 12 ( 2018-12)
    Abstract: Familial hypercholesterolemia (FH) is characterized by inherited high levels of LDL-C (low-density lipoprotein cholesterol) and premature coronary heart disease. Over a thousand low-frequency variants in LDLR, APOB, and PCSK9 have been implicated in FH, but few have been examined at the population level. We aim to estimate the phenotypic effects of a subset of FH variants on LDL-C and clinical outcomes among 331 107 multiethnic participants. Methods: We examined the individual and collective association between putatively pathogenic FH variants included on the Million Veteran Program biobank array and the maximum LDL-C level over an interval of 15 years (maxLDL). We assessed the collective effect on clinical outcomes by leveraging data from 61.7 million clinical encounters. Results: We found 8 out of 16 putatively pathogenic FH variants with ≥30 observed carriers to be significantly associated with elevated maxLDL (9.4–80.2 mg/dL). Phenotypic effects were similar for European Americans and African Americans, despite substantial differences in carrier frequencies. Based on observed effects on maxLDL, we identified a total of 748 carriers (1:443) who had elevated maxLDL (36.5±1.4 mg/dL; P =1.2×10 –152 ), and higher prevalence of clinical diagnoses related to hypercholesterolemia and coronary heart disease in a phenome-wide scan. Adjusted for maxLDL, FH variants collectively associated with higher prevalence of coronary heart disease (odds ratio, 1.59; 95% CI, 1.36–1.86, P =1.1×10 –8 ) but not peripheral artery disease. Conclusions: The distribution and phenotypic effects of putatively pathogenic FH variants were heterogeneous within and across variants. More robust evidence of genotype-phenotype associations of FH variants in multiethnic populations is needed to accurately infer at-risk individuals from genetic screening.
    Type of Medium: Online Resource
    ISSN: 2574-8300
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2927603-2
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  • 8
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 6 ( 2021-06), p. 2027-2034
    Abstract: We aimed to estimate the effect of blood pressure (BP) traits and BP-lowering medications (via genetic proxies) on peripheral artery disease. Approach and Results: Genome-wide association studies summary statistics were obtained for BP, peripheral artery disease (PAD), and coronary artery disease. Causal effects of BP on PAD were estimated by 2-sample Mendelian randomization using a range of pleiotropy-robust methods. Increased systolic BP (SBP), diastolic BP, mean arterial pressure (MAP), and pulse pressure each significantly increased risk of PAD (SBP odds ratio [OR], 1.20 [1.16–1.25] per 10 mm Hg increase, P =1×10 −24 ; diastolic BP OR, 1.27 [1.18–1.35], P =4×10 −11 ; MAP OR, 1.26 [1.19–1.33], P =6×10 −16 ; pulse pressure OR, 1.31 [1.24–1.39], P =9×10 −23 ). The effects of SBP, diastolic BP, and MAP were greater for coronary artery disease than PAD (SBP ratio of OR [ROR], 1.06 [1.0–1.12] , P = 0.04; MAP ratio of OR, 1.15 [1.06–1.26], P =8.6×10 −4 ; diastolic BP ratio of OR, 1.21 [1.08–1.35], P =6.9×10 −4 ). Considered jointly, both pulse pressure and MAP directly increased risk of PAD (pulse pressure OR, 1.26 [1.17–1.35], P =3×10 −10 ; MAP OR, 1.14 [1.06–1.23], P =2×10 −4 ). The effects of antihypertensive medications were estimated using genetic instruments. SBP-lowering via β-blocker (OR, 0.74 per 10 mm Hg decrease in SBP [95% CI, 0.65–0.84]; P =5×10 −6 ), loop diuretic (OR, 0.66 [0.48–0.91], P =0.01), and thiazide diuretic (OR, 0.57 [0.41–0.79], P =6×10 −4 ) associated variants were protective of PAD. Conclusions: Higher BP is likely to cause PAD. BP-lowering through β blockers, loop diuretics, and thiazide diuretics (as proxied by genetic variants) was associated with decreased risk of PAD. Future study is needed to clarify the specific mechanisms by which BP influences PAD.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1494427-3
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  • 9
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 139, No. Suppl_1 ( 2019-03-05)
    Abstract: Introduction: Recent studies suggest a substantial improvement in risk prediction of coronary artery disease (CAD) with polygenic risk scores (PRS). The degree to which this improvement is generalizable to other European (EUR) and non-EUR populations remains unclear. Hypothesis: We hypothesized that genome-wide PRSs trained and validated in the UK Biobank (UKBB) would perform best in external EUR populations and reduce the performance gap in prediction between EURs and African Americans (AA). Methods: We tested our hypothesis in ~91 000 EUR, AA, and Hispanic (HISP) Million Veteran Program (MVP) participants with CAD and ~225 000 non-cases as of July 2017. We created 5 separate weighted PRSs in all participants using: 1) 164 genome-wide significant SNPs for CAD (164SNPs), 2) 46 000 Metabochip SNPs (GRS46K), 3) 1.5 million (M) SNPs from standard pruning & thresholding of CARDIOGRAM+C4D (Khera_P & T), 4) 6.6M SNPs PRS created with LDpred (LDpred_Khera), and 5) 1.7M SNP PRS combining weights of 3 PRSs through meta-analysis (meta-GRS). We estimated age & sex adjusted Odds Ratios (OR) of CAD per standard deviation increase in each PRS using logistic regression and performed sensitivity analyses in subgroups of cases and non-cases. Results: LDpred and meta-GRS performed best among EURs (figure). However, the point estimate of the OR for these PRSs in MVP was notably lower than that observed in the UKBB (1.36 vs. ~1.7). ORs in MVP were higher among participants with early-onset disease (1.39), myocardial infarction (1.52), and revascularization (1.56) but lower for incident events after enrollment (1.27). Performance in HISP was mildly diluted but all PRS performed poorly among AA (figure). Conclusion: Genome-wide PRSs developed in the UKBB transfer best to external EUR populations but may over-estimate risk and do not close the performance gap in prediction between EURs and AAs. Our findings highlight a need for better calibrated PRSs specific to the cohort and race/ethnic group being tested prior to implementation in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1466401-X
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  • 10
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Introduction: CYP2C19 reduced function (RF) alleles (*2, *3) have been shown to impair clopidogrel effectiveness following percutaneous coronary intervention (PCI) in the setting of acute coronary syndromes (ACS); however, this association has not been explored in the Veterans Health Administration. Hypothesis: CYP2C19 RF alleles are associated with major adverse cardiac events (MACE) in patients treated with clopidogrel Methods: MACE and CYP2C19 genotype were determined in MVP participants who underwent PCI between 2009-2017 with 1 year follow-up. Age was restricted to 〈 65 years of age to exclude Veterans likely receiving care outside VHA. DNA extracted from whole blood was genotyped using a customized array and imputed to the 1000 Genomes reference panel. MACE, encompassing all-cause mortality, myocardial infarction and ischemic stroke, was ascertained in VA electronic health records using ICD 9/10 codes. Time to first MACE was determined in the whole cohort and in the subgroup with ACS and stable coronary disease using Kaplan-Meier estimators and Cox proportional hazard models adjusted for clinical covariates and clopidogrel exposure modeled as a time-varying covariate. Results: Among 4,490 Veterans (age 59.1 ± 5 years, 18% African American, 6% Hispanic, 44% ACS) who were prescribed clopidogrel following PCI, 1,261 (28%) had RF CYP2C19 alleles. The overall MACE rate was 7.0%. MACE was associated with ACS as initial presentation, diagnosis of diabetes, chronic kidney disease, peripheral vascular disease, congestive heart failure, history of stroke, prior MI. Among the subgroup presenting with ACS, the adjusted risk of MACE was greater in participants with RF alleles compared to those with wildtype alleles (HR 1.38, 95% CI 1.002-1.916). There was no impact of RF alleles on MACE risk in those in the non-ACS group (HR 1.00, 95% CI 0.702-1.429). Conclusions: These data from the largest integrated health system in the US demonstrate that in Veterans presenting with ACS undergoing PCI, there was a higher risk of MACE in CYP2C19 RF carriers prescribed clopidogrel vs. wildtype carriers. The impact of the CYP2C19-clopidogrel interaction was not observed in the non-ACS patients. Further studies should explore the role of pharmacogenetic testing in Veterans.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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