Faculty Bibliography

Clopidogrel use prior to coronary artery bypass graft surgery in patients presenting with acute coronary syndromes is associated with a greater incidence of procedural related morbidity. We studied the impact of clopidogrel pre-treatment in patients undergoing off-pump versus on-pump coronary revascularization. This report describes a post hoc analysis of 431 on-pump and 165 off-pump cases from a retrospective multicenter study of the impact of preoperative (within 5 days) clopidogrel use on bleeding related outcomes and surgical reintervention. Logistic regression was used to analyze the outcomes with respect to surgery type and clopidogrel exposure while using a propensity score risk adjustment for off-pump surgery. The hospital length of stay (9.3 +/- 5.4 days vs. 8.9 +/- 5.3 days, p = 0.35), major bleeding (21% vs. 20%, p = 0.74) and reoperation (3.7% vs. 4.8%, p = 0.53) were similar between on-pump and off-pump, respectively. In both surgical cohorts, recent clopidogrel use was associated with a greater incidence of major bleeding, reoperation, and transfusion. After multivariable adjustment, the odds ratio of major bleeding (1.76, 95% confidence interval 0.88-3.52 on-pump; 2.37, 95% confidence interval 1.06-5.30 off-pump) and reoperation (4.52, 95% confidence interval 0.58-36.6 in on-pump; 7.05, 95% confidence interval 0.82-60.5 in off-pump) was increased in clopidogrel-treated patients compared to no clopidogrel. Major bleeding and reoperation did not differ significantly between patients undergoing on- or off-pump surgery. Clopidogrel treatment within 5 days prior to surgery increased the risk of bleeding and reoperation in all CABG patients irrespective of whether surgery was performed on- or off-pump.

OBJECTIVE The association between platelet activity, diabetes, and glucometabolic control is uncertain. We aim to investigate mean platelet volume (MPV), a marker of platelet size and platelet activity, with the prevalence of diabetes, metabolic syndrome, and degree of glycemic control. RESEARCH DESIGN AND METHODS This is a retrospective analysis of 13,021 participants in the National Health and Nutrition Examination Survey from 1999 to 2004. Prevalence of diabetes was defined as nonfasting glucose >200 mg/dL, fasting glucose >/=126 mg/dL, or treatment with hypoglycemic agents. Presence of metabolic syndrome was determined by the National Cholesterol Education Program Adult Treatment Panel III definition. Odds ratios and 95% CIs were estimated by logistic regression. RESULTS MPV was significantly higher in subjects with diabetes (8.20 vs. 8.06 femtoliter [fL], P < 0.01) but not in subjects with metabolic syndrome (8.09 vs. 8.07 fL, P = 0.24). For the metabolic syndrome components, MPV was significantly higher in abdominal obesity (P = 0.03) and low HDL (P = 0.04), and not different in high blood pressure (P = 0.07), abnormal glucose metabolism (P = 0.71), or hypertriglyceridemia (P = 0.46). There was a significant correlation between MPV and glucose (P < 0.0001) and between MPV and hemoglobin A(1c) (P < 0.0001) in subjects with diabetes. These correlations were no longer significant in those without diabetes. The adjusted odds of diabetes rose with increasing MPV levels and were most pronounced in subjects with MPV levels exceeding the 90th percentile (>/=9.31 fL). The association between MPV and diabetes was most apparent in those with the poorest glucose control. CONCLUSIONS Mean platelet volume is strongly and independently associated with the presence and severity of diabetes.

Background- Few studies simultaneously investigated lipids and lipoprotein biomarkers as predictors of ischemic stroke. The value of these biomarkers as independent predictors of ischemic stroke remains controversial. METHODS: We conducted a prospective nested case-control study among postmenopausal women from the Women's Health Initiative Observational Study to assess the relationship between fasting lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), lipoproteins (LDL, HDL, and very low-density lipoprotein [VLDL] particle number and size, intermediate-density lipoprotein [IDL] particle number, and lipoprotein (a)), and risk of ischemic stroke. Among women free of stroke at baseline, 774 ischemic stroke patients were matched according to age and race to control subjects, using a 1:1 ratio. RESULTS: In bivariate analysis, baseline triglycerides (P<0.001), IDL particles (P<0.01), LDL particles (P<0.01), VLDL triglyceride (P<0.001), VLDL particles (P<0.01), VLDL size (P<0.001), LDL size (P=0.03), and total/HDL cholesterol ratio (P<0.01) were significantly higher among women with incident ischemic stroke, whereas levels of HDL-C (P<0.01) and HDL size (P<0.01) were lower. No significant baseline difference for total cholesterol (P=0.15), LDL-C (P=0.47), and lipoprotein (a) (P=0.11) was observed. In multivariable analysis, triglycerides (odds ratio for the highest versus lowest quartile, 1.56; 95% confidence interval, 1.13-2.17; P for trend=0.02), VLDL size (odds ratio, 1.59; 95% confidence interval, 1.10-2.28; P for trend=0.03), and IDL particle number (odds ratio, 1.46; 95% confidence interval, 1.04-2.04; P for trend=0.02) were significantly associated with ischemic stroke. CONCLUSIONS: Among a panel of lipid and lipoprotein biomarkers, baseline triglycerides, VLDL size, and IDL particle number were significantly associated with incident ischemic stroke in postmenopausal women.

OBJECTIVES: The objective of this study was to perform a systematic review and meta-analysis of the predictive value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for future cardiovascular events and death in hypertrophic cardiomyopathy (HCM). BACKGROUND: The utility of LGE for detecting myocardial fibrosis is well established. The prognostic value of LGE in HCM has been described in several studies, but controversy exists given the limited power of these studies to predict future events. METHODS: We searched multiple databases including PubMed for studies of LGE in HCM that reported selected clinical outcomes (cardiovascular mortality, sudden cardiac death [SCD], aborted SCD, and heart failure death). We performed a systematic review of the literature and meta-analysis to determine pooled odds ratios for these clinical events. RESULTS: Four studies evaluated 1,063 patients over an average follow-up of 3.1 years. The pooled prevalence of LGE was 60%. The pooled odds ratios (OR) demonstrate that LGE by CMR correlated with cardiac death (pooled OR: 2.92, 95% confidence interval [CI]: 1.01 to 8.42; p = 0.047), heart failure death (pooled OR: 5.68, 95% CI: 1.04 to 31.07; p = 0.045), and all-cause mortality (pooled OR: 4.46, 95% CI: 1.53 to 13.01; p = 0.006), and showed a trend toward significance for predicting sudden death/aborted sudden death (pooled OR: 2.39, 95% CI: 0.87 to 6.58; p = 0.091). CONCLUSIONS: Late gadolinium enhancement by CMR has prognostic value in predicting adverse cardiovascular events among HCM patients. There are significant relationships between LGE and cardiovascular mortality, heart failure death, and all-cause mortality in HCM. Additionally, LGE and SCD/aborted SCD displayed a trend toward significance. The assessment of LGE by CMR has the potential to provide important information to improve risk stratification in HCM in clinical practice.

Background: Light transmission aggregometry (LTA) is considered the gold standard for investigating platelet activity ex vivo. However, LTA protocols are not standardized, and differences in LTA procedure are a potential source of variance in results. Centrifugation speed is an essential component of platelet preparation in LTA, has yet to be standardized, and may affect platelet aggregation results. We sought to investigate the effect of relative centrifugal force (RCF) intensity on LTA results. Methods: Ten healthy controls had venous blood drawn and centrifuged at 150, 200, 300, and 500 g for 10 min. Cell counts in whole blood and platelet-rich plasma (PRP) were measured using a hematology analyzer. LTA was performed using 1.0 mum adenosine diphosphate (ADP) and 0.4 mum epinephrine as an agonist. Aggregation (%) was compared at 60, 120, 180, and 300 s and at maximum aggregation. Results: Centrifugation speed was associated with decreasing platelet count (P < 0.001) and decreasing mean platelet volume (P < 0.001) in PRP. Maximum aggregation decreased with increasing speeds for ADP 1.0 mum (150 g- 89%, 200 g- 93%, 300 g- 71%, 500 g- 17%; P < 0.001). Similar findings were noted at 120 s (150 g- 69%, 200 g- 50%, 300 g- 35%, 500 g- 12%; P < 0.001), 180 s (150 g- 82%, 200 g- 74%, 300 g- 44%, 500 g- 13%; P < 0.001), and 300 s (150 g- 85%, 200 g- 88%, 300 g- 55%, 500 g- 14%; P < 0.001). Consistently, platelet aggregation in response to epinephrine 0.4 mum decreased significantly with increasing centrifuge RCF at 60, 120, 180, 300 s and at maximum aggregation (P < 0.05 for each comparison). Conclusion: Our data demonstrate the importance of centrifugation speed in the interpretation of LTA results, supporting the need for standardization of centrifugation RCF in LTA protocols

Almost one third of annual worldwide mortality is attributed to cardiovascular disease (CVD), making it the leading cause of global death. Dyslipidemia is a well-established risk factor for CVD and plays a pivotal role in the pathogenesis of atherosclerosis. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and lower low-density lipoprotein cholesterol, have emerged as the most effective therapy to date against atherothrombotic CVD. Although their role in secondary prevention of CVD is undisputed, it remains a topic for debate as to how widely they should be used for primary prevention. The Framingham Risk Score and the National Cholesterol Education Program Adult Treatment Panel III guidelines are the cornerstones for the current guidelines for primary prevention statin therapy. Although these guidelines serve as help to evaluate cardiovascular risk and effectively identify many patients who will benefit from statin therapy, there is a growing population of "intermediate-risk" patients who may be undertreated. Additional noninvasive tests may complement the traditional risk scores, potentially expanding the indications for statins.