Mark A Hlatky

Stanford Medicine, Stanford, California, United States

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Publications (448)5403.97 Total impact

  • Mark A Hlatky · Leslee Shaw ·

    Journal of the American College of Cardiology 11/2015; DOI:10.1016/j.jacc.2015.11.002 · 16.50 Impact Factor
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    ABSTRACT: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)?
    BMJ: British medical journal 10/2015; DOI:10.1136/bmj.h5096 · 16.30 Impact Factor
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    ABSTRACT: Background: Fractional flow reserve estimated using computed tomography (FFRCT) might improve evaluation of patients with chest pain. Objectives: The authors sought to determine the effect on cost and quality of life (QOL) of using FFRCT instead of usual care to evaluate stable patients with symptoms suspicious for coronary disease. Methods: Symptomatic patients without known coronary disease were enrolled into 2 strata based on whether invasive or noninvasive diagnostic testing was planned. In each stratum, consecutive observational cohorts were evaluated with either usual care or FFRCT. The number of diagnostic tests, invasive procedures, hospitalizations, and medications during 90-day follow-up were multiplied by U.S. cost weights and summed to derive total medical costs. Changes in QOL from baseline to 90 days were assessed using the Seattle Angina Questionnaire, the EuroQOL, and a visual analog scale. Results: In the 584 patients, 74% had atypical angina, and the pre-test probability of coronary disease was 49%. In the planned invasive stratum, mean costs were 32% lower among the FFRCT patients than among the usual care patients ($7,343 vs. $10,734 p < 0.0001). In the noninvasive stratum, mean costs were not significantly different between the FFRCT patients and the usual care patients ($2,679 vs. $2,137, p = 0.26). In a sensitivity analysis, when the cost weight of FFRCT was set to 7 times that of computed tomography angiography, the FFRCT group still had lower costs than the usual care group in the invasive testing stratum ($8,619 vs. $ 10,734, p < 0.0001), whereas in the noninvasive testing stratum, when the cost weight of FFRCT was set to half that of computed tomography angiography, the FFRCT group had higher costs than the usual care group ($2,766 vs. $2,137, p = 0.02). Each QOL score improved in the overall study population (p < 0.0001). In the noninvasive stratum, QOL scores improved more in FFRCT patients than in usual care patients: Seattle Angina Questionnaire 19.5 versus 11.4, p = 0.003; EuroQOL 0.08 versus 0.03, p = 0.002; and visual analog scale 4.1 versus 2.3, p = 0.82. In the invasive cohort, the improvements in QOL were similar in the FFRCT and usual care patients. Conclusions: An evaluation strategy based on FFRCT was associated with less resource use and lower costs within 90 days than evaluation with invasive coronary angiography. Evaluation with FFRCT was associated with greater improvement in quality of life than evaluation with usual noninvasive testing. (Prospective Longitudinal Trial of FFRCT: Outcomes and Resource Impacts [PLATFORM]; NCT01943903).
    Journal of the American College of Cardiology 10/2015; DOI:10.1016/j.jacc.2015.09.051 · 16.50 Impact Factor
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    ABSTRACT: Importance: Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk. Objective: To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy in patients with uncomplicated hypertension undergoing noncardiac surgery. Design, setting, and participants: Association study based on in-hospital records and out-of-hospital pharmacotherapy use using a Danish nationwide cohort of patients with uncomplicated hypertension treated with at least 2 antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. Interventions: Various antihypertensive treatment regimens, chosen as part of usual care. Main outcomes and measures: Thirty-day risk of MACEs (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). Results: The baseline characteristics of the 14 644 patients who received β-blockers (65% female, mean [SD] age, 66.1 [12.0] years) were similar to those of the 40 676 patients who received other antihypertensive drugs (57% female, mean [SD] age, 65.9 [11.8] years). Thirty-day MACEs occurred in 1.3% of patients treated with β-blockers compared with 0.8% of patients not treated with β-blockers (P < .001). β-Blocker use was associated with increased risks of MACEs in 2-drug combinations with RAS inhibitors (odds ratio [OR], 2.16 [95% CI, 1.54-3.04]), calcium antagonists (OR, 2.17 [95% CI, 1.48-3.17]), and thiazides (OR, 1.56 [95% CI, 1.10-2.22]), compared with the reference combination of RAS inhibitors and thiazides. Results were similar for all-cause mortality. Risk of MACEs associated with β-blocker use seemed especially pronounced for patients at least 70 years old (number needed to harm [NNH], 140 [95% CI, 86-364]), for men (NNH, 142 [95% CI, 93-195]), and for patients undergoing acute surgery (NNH, 97 [95% CI, 57-331]), compared with patients younger than 70 years, women, and patients undergoing elective surgery, respectively. Conclusions and relevance: Antihypertensive treatment with a β-blocker may be associated with increased risks of perioperative MACEs and all-cause mortality in patients with uncomplicated hypertension.
    JAMA Internal Medicine 10/2015; DOI:10.1001/jamainternmed.2015.5346 · 13.12 Impact Factor
  • Jacqueline Baras Shreibati · Mark A. Hlatky ·

    Journal of the American College of Cardiology 10/2015; 66(17):1886-1887. DOI:10.1016/j.jacc.2015.08.861 · 16.50 Impact Factor
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    ABSTRACT: Background: -Recent genome wide association studies (GWAS) have identified 49 single nucleotide polymorphisms (SNPs) associated with clinical CAD. The mechanism by which these loci influence risk remains largely unclear. Methods and results: -We examined the association between a genetic risk score (GRS) composed of high-risk alleles at the 49 SNPs and the degree of subclinical coronary atherosclerosis in 7,798 participants from six studies stratified into four age groups at the time of assessment (15-34, 35-54, 55-74, >75 years). Atherosclerosis was quantified by staining and direct visual inspection of the right coronary artery in the youngest group, and by scanning for coronary artery calcification in the remaining groups. We defined cases as subjects within the top quartile of degree of atherosclerosis in three groups and as subjects with a CAC>0 in the fourth (35-54 years) where less than one quarter had any CAC. In our meta-analysis of all strata, we found one SD increase in the GRS increased the risk of advanced subclinical coronary atherosclerosis by 36% (p=8.3×10(-25)). This increase in risk was significant in all four age groups including the youngest group where atherosclerosis consisted primarily of raised lesions without macroscopic evidence of plaque rupture or thrombosis. Results were similar when we restricted the GRS to 32 SNPs not associated with traditional risk factors (TRFs) and/or when we adjusted for TRFs. Conclusions: -A GRS for clinical CAD is associated with advanced subclinical coronary atherosclerosis throughout the life-course. This association is apparent even at the earliest, uncomplicated stages of atherosclerosis.
    Circulation Cardiovascular Genetics 09/2015; DOI:10.1161/CIRCGENETICS.114.001071 · 4.60 Impact Factor
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    Circulation 09/2015; DOI:10.1161/CIR.0000000000000312 · 14.43 Impact Factor
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    ABSTRACT: Background: Fractional flow reserve (FFR) measured by coronary computed tomography angiography (FFRCT) has been validated against invasive FFR. However, there are no data on how the use of FFRCT affects patient care and outcomes. The aim of this study is to compare standard practice guided by usual care testing to FFRCT-guided management in symptomatic subjects with suspected coronary artery disease (CAD). Methods: In this prospective nonrandomized trial, symptomatic patients with suspected CAD will be enrolled in 2 consecutive cohorts: a usual care-guided pathway (cohort 1) and an FFRCT-guided pathway (cohort 2). Each cohort is divided into 2 groups according to whether noninvasive or invasive diagnostic testing was planned before enrollment. In all subjects, the patient's clinical team will review all diagnostic test results and determine a treatment strategy. A total sample size of 580 subjects will be enrolled and followed up for 12 months. Results: The primary end point is the comparison of the percentage of patients with planned invasive testing who have a catheterization (invasive coronary angiography) within 90 days from initial assessment, which does not show a significant stenosis (defined as coronary artery stenosis >50% or invasive FFR ≤0.80). Secondary end points include the rate of invasive coronary angiography without obstructive CAD in those with planned noninvasive testing and, in all groups, noninferiority of resource use, quality of life, medical radiation exposure, and major adverse cardiac events up to 365 days of follow-up. Conclusions: The study compares clinical and economic outcomes based on diagnostic evaluation using FFRCT with that based on standard diagnostic strategies.
    American heart journal 09/2015; 170(3):438-446.e44. DOI:10.1016/j.ahj.2015.06.002 · 4.46 Impact Factor
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    ABSTRACT: Aims: High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. Methods and results: The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31). Conclusion: Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF.
    European Heart Journal 09/2015; DOI:10.1093/eurheartj/ehv423 · 15.20 Impact Factor

  • Journal of the American College of Cardiology 09/2015; DOI:10.1016/j.jacc.2015.09.001 · 16.50 Impact Factor
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    ABSTRACT: In symptomatic patients with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) improves patient selection for invasive coronary angiography (ICA) compared with functional testing. The impact of measuring fractional flow reserve by CTA (FFRCT) is unknown. At 11 sites, 584 patients with new onset chest pain were prospectively assigned to receive either usual testing (n = 287) or CTA/FFRCT (n = 297). Test interpretation and care decisions were made by the clinical care team. The primary endpoint was the percentage of those with planned ICA in whom no significant obstructive CAD (no stenosis ≥50% by core laboratory quantitative analysis or invasive FFR < 0.80) was found at ICA within 90 days. Secondary endpoints including death, myocardial infarction, and unplanned revascularization were independently and blindly adjudicated. Subjects averaged 61 ± 11 years of age, 40% were female, and the mean pre-test probability of obstructive CAD was 49 ± 17%. Among those with intended ICA (FFRCT-guided = 193; usual care = 187), no obstructive CAD was found at ICA in 24 (12%) in the CTA/FFRCT arm and 137 (73%) in the usual care arm (risk difference 61%, 95% confidence interval 53-69, P< 0.0001), with similar mean cumulative radiation exposure (9.9 vs. 9.4 mSv, P = 0.20). Invasive coronary angiography was cancelled in 61% after receiving CTA/FFRCT results. Among those with intended non-invasive testing, the rates of finding no obstructive CAD at ICA were 13% (CTA/FFRCT) and 6% (usual care; P = 0.95). Clinical event rates within 90 days were low in usual care and CTA/FFRCT arms. Computed tomographic angiography/fractional flow reserve by CTA was a feasible and safe alternative to ICA and was associated with a significantly lower rate of invasive angiography showing no obstructive CAD. The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.
    European Heart Journal 09/2015; DOI:10.1093/eurheartj/ehv444 · 15.20 Impact Factor
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    ABSTRACT: Cardiac resynchronization therapy (CRT) reduces mortality and heart failure hospitalizations in patients with mild heart failure. To estimate the cost-effectiveness of adding CRT to an implantable cardioverter-defibrillator (CRT-D) compared with implantable cardioverter-defibrillator (ICD) alone among patients with left ventricular systolic dysfunction, prolonged intraventricular conduction, and mild heart failure. Markov decision model. Clinical trials, clinical registries, claims data from Centers for Medicare & Medicaid Services, Centers for Disease Control and Prevention life tables. Patients age 65 years or older with a left ventricular ejection fraction (LVEF) of 30% or less, QRS duration of 120 milliseconds or more, and New York Heart Association (NYHA) class I or II symptoms. Lifetime. Societal. CRT-D or ICD alone. Life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Use of CRT-D increased life expectancy (9.8 years versus 8.8 years), QALYs (8.6 years versus 7.6 years), and costs ($286 500 versus $228 600), yielding a cost per QALY gained of $61 700. The cost-effectiveness of CRT-D was most dependent on the degree of mortality reduction: When the risk ratio for death was 0.95, the ICER increased to $119 600 per QALY. More expensive CRT-D devices, shorter CRT-D battery life, and older age also made the cost-effectiveness of CRT-D less favorable. The estimated mortality reduction for CRT-D was largely based on a single trial. Data on patients with NYHA class I were limited. The cost-effectiveness of CRT-D in patients with NYHA class I symptoms remains uncertain. In patients with an LVEF of 30% or less, QRS duration of 120 milliseconds or more, and NYHA class II symptoms, CRT-D appears to be economically attractive relative to ICD alone when a reduction in mortality is expected. National Institutes of Health, University of Copenhagen, U.S. Department of Veterans Affairs.
    Annals of internal medicine 08/2015; 163(6). DOI:10.7326/M14-1804 · 17.81 Impact Factor
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    ABSTRACT: Background Galectin-3 (Gal-3) is a novel fibrosis biomarker. We ascertained: 1) the correlates of Gal-3, and 2) its association with incident heart failure among 1312 participants in The ADVANCE study (871 subjects with acute myocardial infarction [AMI] and 441 subjects with stable angina). Methods Cohort design, with Gal-3 measured in stored baseline serum samples (2002-04). After a median (SD) follow-up of 8.1 (3.2) years, 74 incident heart failure events were documented. Results The significant independent correlates of Gal-3 were age, gender, diabetes, C-reactive protein and estimated glomerular filtration rate. In Cox regression with adjustment for these variables plus race, CAD presentation, smoking status, body mass index, hypertension and cholesterol lowering drugs, there was a 1.51-fold (95% CI, 1.24 to 1.85; p < 0.0001) increased hazard of heart failure for each SD linear increment in Gal-3. In the fully-adjusted model, quartile four of Gal-3 (relative to quartile one) was associated with 2.1-fold increased hazard of heart failure (95% CI, 1.05 to 4.2). The C-statistic increased to 0.78 from 0.75 (p = 0.12) and the net reclassification index was 0.13 (SE = 0.06; p = 0.03) after adding Gal-3 quartiles to the model containing all risk factors. Conclusions Gal-3 is a useful marker of heart failure risk among patients with pre-existing coronary disease and may play an etiological role in the development of heart failure.
    08/2015; 5. DOI:10.1016/j.ctrsc.2015.08.002

  • Clinical Infectious Diseases 06/2015; 61(7). DOI:10.1093/cid/civ517 · 8.89 Impact Factor
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    ABSTRACT: Conclusive evidence is lacking regarding the benefits and risks of performing off-pump versus on-pump coronary artery bypass graft (CABG) for patients with diabetes. This study aims to compare clinical outcomes after off-pump and on-pump procedures for patients with diabetes. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial enrolled patients with type 2 diabetes and documented coronary artery disease, 615 of whom underwent CABG during the trial. The procedural complications, 30-day outcomes, long-term clinical and functional outcomes were compared between the off-pump and on-pump groups overall and within a subset of patients matched on propensity score. On-pump CABG was performed in 444 (72%) patients, and off-pump CABG in 171 (28%). The unadjusted 30-day rate of death/myocardial infarction (MI)/stroke was significantly higher after off-pump CABG (7.0 vs 2.9%, P = 0.02) despite fewer complications (10.3 vs 20.7%, P = 0.003). The long-term risk of death [adjusted hazard ratio (aHR): 1.41, P = 0.2197] and major cardiovascular events (death, MI or stroke) (aHR: 1.47, P = 0.1061) did not differ statistically between the off-pump and on-pump patients. Within the propensity-matched sample (153 pairs), patients who underwent off-pump CABG had a higher risk of the composite outcome of death, MI or stroke (aHR: 1.83, P = 0.046); the rates of procedural complications and death did not differ significantly, and there were no significant differences in the functional outcomes. Patients with diabetes had greater risk of major cardiovascular events long-term after off-pump CABG than after on-pump CABG. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 05/2015; DOI:10.1093/ejcts/ezv170 · 3.30 Impact Factor
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    ABSTRACT: Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors. We identified 15 288 women from the Women's Health Initiative Biomarkers studies with no history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993-1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-high-density lipoprotein-cholesterol ratio TG/HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which occurred in 894 (5.8%) women. Insulin resistance was associated with CVD risk after adjusting for age and race/ethnicity with hazard ratios (95% confidence interval [CI]) per doubling in insulin of 1.21 (CI, 1.12-1.31), in HOMA-IR of 1.19 (CI, 1.11-1.28), in TG/HDL-C of 1.35 (CI, 1.26-1.45), and for impaired fasting glucose of 1.31 (CI, 1.05-1.64). Although insulin, HOMA-IR, and TG/HDL-C remained associated with increased CVD risk after adjusting for most CVD risk factors, none remained significant after adjusting for HDL-C: hazard ratios for insulin, 1.06 (CI, 0.98-1.16); for HOMA-IR, 1.06 (CI, 0.98-1.15); for TG/HDL-C, 1.11 (CI, 0.99-1.25); and for glucose, 1.20 (CI, 0.96-1.50). Insulin resistance measures did not improve CVD risk discrimination and reclassification. Measures of insulin resistance were no longer associated with CVD risk after adjustment for high-density lipoprotein-cholesterol and did not provide independent prognostic information in postmenopausal women without diabetes mellitus. URL: Unique identifier: NCT00000611. © 2015 American Heart Association, Inc.
    Circulation Cardiovascular Quality and Outcomes 05/2015; 8(3). DOI:10.1161/CIRCOUTCOMES.114.001563 · 5.66 Impact Factor
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    ABSTRACT: This report evaluates incidence of cardiovascular disease (CVD) morbidity and mortality over 10 years among the >160,000 postmenopausal women in the Women's Health Initiative (WHI) in relation to self-reported RA, disease modifying anti-rheumatic drugs (DMARD) use, anti-CCP+, RF+, CVD risk factors, joint pain, and inflammation (white blood cell (WBC) count and IL-6.) Methods: Anti-CCP and RF were measured on a sample (n=9,988) of WHI participants with self-reported RA. RA was classified as self-reported RA plus anti-CCP+ positivity and/or use of DMARDs. Self-reported RA that was both anti-CCP- and DMARD- was classified as "unverified RA." Age-adjusted rates of coronary heart disease (CHD), stroke, CVD, fatal CVD and total mortality were higher for women with RA vs. no RA, with multivariable-adjusted HR(95%CI) of 1.46(1.17, 1.83) for CHD, and 2.55(1.86, 3.51) for fatal CVD. Within RA, anti-CCP+ and RF+ were not significantly associated with higher risk of any outcomes, despite slightly higher risk of fatal CVD and death for anti-CCP+ vs. anti-CCP- RA. Joint pain severity and CVD risk factors were strongly associated with CVD risk, even for women with no RA. CVD incidence was increased for RA vs. no RA at almost all risk factor levels, except low levels of joint pain or inflammation. Within RA, inflammation was more strongly associated with fatal CVD and total mortality than CHD or CVD. Among postmenopausal women, RA was associated with 1.5-2.5 higher CVD risk, strongly associated with CV risk factors, joint pain severity, and inflammation, but similar for anti-CCP+ and RF+. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    Arthritis and Rheumatology 05/2015; 67(9). DOI:10.1002/art.39198
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    ABSTRACT: It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups. We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m(2)) as normal weight (body mass index 18.5 to <25), overweight (body mass index 25 to <30), or obese (body mass index ≥30) and by metabolic health, defined first as the metabolic syndrome (metabolically unhealthy: ≥3 metabolic abnormalities) and second as the number of metabolic abnormalities. We used Cox proportional hazards regression to assess associations between baseline characteristics and cardiovascular risk. Over 13 years of follow-up, 1101 women had a first cardiovascular disease event (coronary heart disease or ischemic stroke). Among black women without metabolic syndrome, overweight women had higher adjusted cardiovascular risk than normal weight women (hazard ratio [HR] 1.49), whereas among white women without metabolic syndrome, overweight women had similar risk to normal weight women (HR 0.92, interaction P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased in black women who were overweight (HR 1.77) or obese (HR 2.17) but not in white women who were overweight (HR 0.98) or obese (HR 1.06). Overweight and obese women with ≤1 metabolic abnormality did not have increased cardiovascular risk, regardless of race or ethnicity. Metabolic abnormalities appeared to convey more cardiovascular risk among black women. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 04/2015; 4(5). DOI:10.1161/JAHA.114.001695 · 4.31 Impact Factor
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    ABSTRACT: Background: To characterize the association of antiretroviral drug combinations on risk of cardiovascular events. Methods: Certain antiretroviral medications for human immunodeficiency virus (HIV) have been implicated in increasing risk of cardiovascular disease. However, antiretroviral drugs are typically prescribed in combination. We characterized the association of current exposure to antiretroviral drug combinations on risk of cardiovascular events including myocardial infarction, stroke, percutaneous coronary intervention, and coronary artery bypass surgery. We used the Veterans Health Administration Clinical Case Registry to analyze data from 24 510 patients infected with HIV from January 1996 through December 2009. We assessed the association of current exposure to 15 antiretroviral drugs and 23 prespecified combinations of agents on the risk of cardiovascular event by using marginal structural models and Cox models extended to accommodate time-dependent variables. Results: Over 164 059 person-years of follow-up, 934 patients had a cardiovascular event. Current exposure to abacavir, efavirenz, lamivudine, and zidovudine was significantly associated with increased risk of cardiovascular event, with odds ratios ranging from 1.40 to 1.53. Five combinations were significantly associated with increased risk of cardiovascular event, all of which involved lamivudine. One of these-efavirenz, lamivudine, and zidovudine-was the second most commonly used combination and was associated with a risk of cardiovascular event that is 1.60 times that of patients not currently exposed to the combination (odds ratio = 1.60, 95% confidence interval, 1.25-2.04). Conclusions: In the VA cohort, exposure to both individual drugs and drug combinations was associated with modestly increased risk of a cardiovascular event.
    Clinical Infectious Diseases 04/2015; 61(3). DOI:10.1093/cid/civ316 · 8.89 Impact Factor
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    ABSTRACT: Background Platelet inhibition after percutaneous coronary intervention (PCI) reduces the risk of myocardial infarction (MI) but increases the risk of bleeding. MIs and bleeds during the index hospitalization for PCI are known to negatively affect long-term outcomes. The impact of spontaneous bleeding occurring after discharge on long-term mortality is unknown. Objectives This study sought to examine, in a real-world cohort, the association between spontaneous major bleeding or MI after PCI and long-term mortality. Methods We conducted a retrospective cohort study of patients ≥30 years of age who underwent a PCI between 1996 and 2008 in an integrated healthcare delivery system. We used extended Cox regression to examine the associations of spontaneous bleeding and MI with all-cause mortality, after adjustment for time-updated demographics, comorbidities, periprocedural events, and longitudinal medication exposure. Results Among 32,906 patients who had a PCI and survived the index hospitalization, 530 had bleeds and 991 had MIs between 7 and 365 days post-discharge. There were 4,048 deaths over a mean follow-up of 4.42 years. The crude annual death rate after a spontaneous bleed (9.5%) or MI (7.6%) was higher than among patients who experienced neither event (2.6%). Bleeding was associated with an increased rate of death (adjusted hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.30 to 2.00), similar to that after an MI (HR: 1.91; 95% CI: 1.62 to 2.25). The association of bleeding with death remained significant after additional adjustment for the longitudinal use of antiplatelet agents. Conclusions Spontaneous bleeding after a PCI was independently associated with higher long-term mortality, and conveyed a risk comparable to that of an MI during follow-up. This tradeoff between efficacy and safety bolsters the argument for personalizing antiplatelet therapy after PCI on the basis of the patient's long-term risk of both thrombotic and bleeding events.
    Journal of the American College of Cardiology 04/2015; 65(14):1411-20. DOI:10.1016/j.jacc.2015.01.047 · 16.50 Impact Factor

Publication Stats

27k Citations
5,403.97 Total Impact Points


  • 1991-2015
    • Stanford Medicine
      • • Department of Health Research and Policy
      • • Division of Cardiovascular Medicine
      • • Stanford School of Medicine
      • • Division of Health Services Research
      Stanford, California, United States
    • Stanford University
      • • Department of Medicine
      • • Department of Health Research and Policy
      • • Division of Cardiovascular Medicine
      Palo Alto, California, United States
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2014
    • Lund University
      • Department of Cardiology
      Lund, Skåne, Sweden
  • 2012
    • Palo Alto University
      Palo Alto, California, United States
  • 2011
    • American College of Cardiology
      Washington, Washington, D.C., United States
  • 2010
    • Brigham and Women's Hospital
      Boston, Massachusetts, United States
  • 2007
    • Centers for Disease Control and Prevention
      • National Center for Chronic Disease Prevention and Health Promotion
      Druid Hills, GA, United States
  • 1999-2002
    • VA Palo Alto Health Care System
      Palo Alto, California, United States
  • 1984-2002
    • Duke University
      • Department of Medicine
      Durham, North Carolina, United States
  • 1996
    • University of Pittsburgh
      • Department of Epidemiology
      Pittsburgh, Pennsylvania, United States
  • 1995
    • Montreal Heart Institute
      Montréal, Quebec, Canada
  • 1994
    • University of California, San Francisco
      • School of Nursing
      San Francisco, California, United States
  • 1983-1993
    • Duke University Medical Center
      • • Department of Surgery
      • • Division of Cardiology
      • • Department of Medicine
      Durham, North Carolina, United States
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States
  • 1986
    • National Institute on Aging
      Baltimore, Maryland, United States