Faculty Bibliography

BACKGROUND: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate to high intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat to target approach. Whether percentage low density lipoprotein cholesterol (LDL-C) reduction or attained LDL-C levels add incremental prognostic value to statin dose is not known. METHODS: Patients in the TNT, IDEAL and SPARCL trials (patient-level data) randomized to a statin arm (atorvastatin 80mg/10mg or simvastatin 20mg) were chosen. Patients were divided into groups based on attained LDL-C levels (70 mg/dl) and percent LDL-C reduction (>/=50% vs. <50%). Primary outcome was major cardiovascular event defined as death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke. Incremental prognostic value was assessed by using a forward conditional Cox proportional hazards model. Two models were tested: Model 1: Step 1-statin dose; Step 2-add attained LDL-C levels (continuous variable); Step 3-add percent LDL-C reduction (continuous variable). Model 2: step 2 and 3 were reversed. RESULTS: Among 13,937 patients included in this study, percent LDL-C reduction added incremental prognostic value over both statin dose and attained LDL-C levels (Global chi2 increased from 3.64 to 26.1 to 47.5; P<0.0001). However, attained LDL-C level did not provide incremental prognostic value over statin dose and percent LDL-C reduction (Global chi2 increased from 3.64 to 47.5 to 47.5; P<0.0001 and 0.94 respectively). Among patients with attained LDL-C /=50%. CONCLUSIONS: In patients with atherosclerotic cardiovascular disease, percent LDL-C reduction provides incremental prognostic value over statin dose and attained LDL-C levels. However, the attained LDL-C level does not provide additional prognostic value over statin dose and percent LDL-C reduction.

Previous studies have debated the notion that low blood pressure (BP) during treatment, particularly diastolic (DBP), is associated with increased risk of cardiovascular disease. We evaluated the impact of low BP on cardiovascular outcomes in a high-risk population of 15,244 hypertensive patients, almost half of whom had a history of coronary artery disease (CAD). In the prospective Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, patients were randomized to valsartan or amlodipine regimens and followed for 4.2 years (mean) with no difference in the primary cardiovascular endpoint. A Cox proportional hazards model was used to evaluate the relationship between average on-treatment BP and clinical outcomes. The relationship between BP and cardiovascular events was adjusted for age, gender and body mass index, and baseline qualifying risk factors and diseases (smoking, high total cholesterol, diabetes mellitus, proteinuria, CAD, previous stroke and left ventricular hypertrophy). DBP >/= 90 mmHg, compared with < 90 mmHg, was associated with increased incidence of the primary cardiovascular endpoint (all cardiac events); however, DBP < 70 mmHg, compared with >/= 70 mmHg, was not associated with increased incidence after covariate adjustment (no J-shaped curve). Similar results were observed for death, myocardial infarction (MI), heart failure and stroke, considered separately. Nadir for MI was at DBP of 76 mmHg and for stroke 60 mmHg. The ratio of MI to stroke increased with lower DBP. In CAD patients the MI to stroke ratio was more pronounced than in patients without CAD but there was no significant J-curve in either group. Systolic BP >/= 150 but not < 130 mmHg, compared with 130-149 mmHg, similarly was associated with increased risk for primary outcome. In conclusion, patients in BP strata >/= 150/90 mmHg, but not patients in BP strata < 130/70 mmHg, were at increased risk for adverse outcomes in this hypertensive, high-risk population. Although benefit in preventing MI in relation to preventing stroke levels off for the lowest BPs, these data provide no support for a J-curve in the treatment of high-risk hypertensive patients . The increase in the ratio of MI to stroke with lower DBP indicates target organ heterogeneity in that the optimal on-treatment DBP for cerebroprotection is below that for cardioprotection.

OBJECTIVE: To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI-S) who also require chronic oral anticoagulation. BACKGROUND: Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI-S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. METHODS: A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI-S or MI and requiring chronic anticoagulation. Primary outcome was all-cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. RESULTS: A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow-up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all-cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61-1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51-1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35-1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03-1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38-0.92, P = 0.02]. CONCLUSIONS: All-cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. (c) 2015 Wiley Periodicals, Inc.

Background: Coronary artery disease (CAD) and left ventricular hypertrophy (LVH) are prevalent in the chronic kidney disease (CKD) and renal transplant population. We hypothesised that the myocardial oxygenation response to stress would be impaired in CKD Methods: Fifty-three subjects: twenty-three subjects with CKD, ten renal transplant (RT) recipients, ten hypertensive (HT) controls, and ten normal controls without known heart disease underwent CMR scanning at 3T. The RT and HT groups also had late gadolinium CMR to assess infarction/ replacement fibrosis. The CKD group underwent 2D echocardiography strain to assess fibrosis. Results: A total of 2898 myocardial segments (1200 segments in CKD patients, 552 segments in RT, 480 segments in HT, and 666 segments in normal controls) were compared using linear mixed modelling. Diabetes mellitus (p= 0.47) and hypertension (p= 0.57) were similar between CKD, RT, and HT groups. The mean BOLD SI change was significantly lower in the CKD and RT groups compared to HT controls and normal controls (-0.89 +/- 10.63 in CKD versus 5.66 +/- 7.87 in RT versus 15.54 +/- 9.58 in HT controls, p< 0.0001). BOLD SI Change was associated with eGFR (beta= 0.16, 95% CI= 0.10 to 0.22, p<0.0001). Left ventricular mass index and left ventricular septal wall diameter was similar between the CKD pre-dialysis, RT, and HT groups. None of the CKD patients had impaired global longitudinal strain (GLS) and none of the RT group had late gadolinium hyperenhancement. Conclusion: Myocardial oxygenation response to stress is impaired in CKD and RT patients, and unlikely to be solely accounted for by the presence of diabetes mellitus