Judith Hsia

Clinical ResearchRisk Reduction TherapyCardiovascular Event Reduction and Adverse Events Among Subjects Attaining Low-Density Lipoprotein Cholesterol <50 mg/dl With Rosuvastatin: The JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)

OBJECTIVESnThe purpose of this study was to assess the impact on cardiovascular and adverse events of attaining low-density lipoprotein cholesterol (LDL-C) levels <50 mg/dl with rosuvastatin in apparently healthy adults in the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial.nnnBACKGROUNDnThe safety and magnitude of cardiovascular risk reduction conferred by treatment to LDL-C levels below current recommended targets remain uncertain.nnnMETHODSnA cohort of 17,802 apparently healthy men and women with high-sensitivity C-reactive protein ≥2 mg/l and LDL-C <130 mg/dl were randomly allocated to rosuvastatin 20 mg daily or placebo, and followed up for all-cause mortality, major cardiovascular events, and adverse events. In a post-hoc analysis, participants allocated to rosuvastatin were categorized as to whether or not they had a follow-up LDL-C level <50 mg/dl.nnnRESULTSnDuring a median follow-up of 2 years (range up to 5 years), rates of the primary trial endpoint were 1.18, 0.86, and 0.44 per 100 person-years in the placebo group (n = 8,150) and rosuvastatin groups without LDL-C <50 mg/dl (n = 4,000) or with LDL-C <50 mg/dl (n = 4,154), respectively (fully-adjusted hazard ratio: 0.76; 95% confidence interval: 0.57 to 1.00 for subjects with no LDL-C <50 mg/dl vs. placebo and 0.35, 95% confidence interval: 0.25 to 0.49 for subjects attaining LDL-C <50 mg/dl; p for trend <0.0001). For all-cause mortality, corresponding event rates were 0.67, 0.65, and 0.39 (p for trend = 0.004). Rates of myalgia, muscle weakness, neuropsychiatric conditions, cancer, and diabetes mellitus were not significantly different among rosuvastatin-allocated participants with and without LDL-C <50 mg/dl.nnnCONCLUSIONSnAmong adults with LDL-C <130 mg/dl and high-sensitivity C-reactive protein ≥2 mg/l, rosuvastatin-allocated participants attaining LDL-C <50 mg/dl had a lower risk of cardiovascular events without a systematic increase in reported adverse events.

Effects of Rosuvastatin and Atorvastatin on Low-Density and High-Density Lipoprotein Particle Concentrations in Patients With Metabolic Syndrome: A Randomized, Double-Blind, Controlled Study

OBJECTIVE The purpose of this study was to examine the effects of statin therapy on lipoprotein particle concentrations in patients with the metabolic syndrome. Changes in lipoprotein particle concentration may predict the risk of coronary heart disease more accurately than lipoprotein cholesterol levels. RESEARCH DESIGN AND METHODS Patients with dyslipidemia and the metabolic syndrome (n = 318) were randomly assigned in a double-blind study comparing 10 mg rosuvastatin (RSV), 10 mg atorvastatin, or placebo daily for 6 weeks. From weeks 6 to 12, patients in the RSV and placebo groups received 20 mg RSV, whereas the ATV group increased their dose to 20 mg daily. Lipoprotein particle concentrations were measured by nuclear magnetic resonance spectroscopy, LDL cholesterol was measured by β-quantification, and other lipoproteins were measured by standard methods at baseline, 6 weeks, and 12 weeks. Lipoprotein levels were compared by analysis of covariance. RESULTS Statins reduced LDL particle concentration less than LDL cholesterol (−30 to −38 vs. −38 to −51%). Reductions were greater with RSV than with ATV (P < 0.05 for LDL particle concentration and P < 0.001 for LDL cholesterol). Most patients attained LDL cholesterol <2.59 mmol/l (100 mg/dl) at 12 weeks (80% with RSV and 59% with ATV; P = 0.003), but only 27% of patients receiving RSV and 19% receiving ATV attained the goal of LDL particle concentration <1,000 nmol/l (P = 0.07). CONCLUSIONS In patients with the metabolic syndrome, statin-induced changes in LDL cholesterol do not accurately reflect changes in LDL particle concentration. Consequently, despite attainment of LDL cholesterol goals, these patients may retain considerable residual coronary heart disease risk.

Predictors of Heart Failure in Patients With Stable Coronary Artery DiseaseCLINICAL PERSPECTIVE

Background—Heart failure (HF) is a disease commonly associated with coronary artery disease. Most risk models for HF development have focused on patients with acute myocardial infarction. The Prevention of Events with Angiotensin-Converting Enzyme Inhibition population enabled the development of a risk model to predict HF in patients with stable coronary artery disease and preserved ejection fraction. Methods and Results—In the 8290, Prevention of Events with Angiotensin-Converting Enzyme Inhibition patients without preexisting HF, new-onset HF hospitalizations, and fatal HF were assessed over a median follow-up of 4.8 years. Covariates were evaluated and maintained in the Cox regression multivariable model using backward selection if P<0.05. A risk score was developed and converted to an integer-based scoring system. Among the Prevention of Events with Angiotensin-Converting Enzyme Inhibition population (age, 64±8; female, 18%; prior myocardial infarction, 55%), there were 268 cases of fatal and nonfatal HF. Twelve characteristics were associated with increased risk of HF along with several baseline medications, including older age, history of hypertension, and diabetes. Randomization to trandolapril independently reduced the risk of HF. There was no interaction between trandolapril treatment and other risk factors for HF. The risk score (range, 0 to 21) demonstrated excellent discriminatory power (c-statistic 0.80). Risk of HF ranged from 1.75% in patients with a risk score of 0% to 33% in patients with risk score ≥16. Conclusion—Among patients with stable coronary artery disease and preserved ejection fraction, traditional and newer factors were independently associated with increased risk of HF. Trandolopril decreased the risk of HF in these patients with preserved ejection fraction.

Late potentials and their relation to ventricular function in human immunodeficiency virus infection

Signal-averaged electrocardiograms were performed in 225 patients with serologic evidence of human immunodeficiency virus infection as part of a prospective longitudinal study of patients with HIV-associated heart disease and 12 seronegative control subjects. The duration of signal-averaged QRS vector, root-mean-square voltage of the terminal 40 ms of the vector magnitude and the duration of the low-amplitude (less than 40 microV) signal were determined during serial visits at 4-month intervals. One or more of these variables was abnormal on initial visit in 59 of patients (26%); QRS duration was greater than 114 ms in 9 patients (4%), root-mean-square voltage less than 20 microV in 55 patients (24%) and low-amplitude signal duration greater than 39 ms in 43 (19%). In contrast, none of the seronegative control subjects had any abnormal variables (p less than 0.03). During follow-up (mean 10 +/- 8 months), 26 patients with initially normal studies developed abnormal variables and 24 with abnormal signal-averaged electrocardiograms reverted to normal. Left ventricular contractility was assessed by echocardiography using the rate-corrected velocity of fiber shortening-end-diastolic wall stress relation. Late potentials were not related to contractile abnormalities. Clinical arrhythmias were rare and did not appear more frequent among patients with late potentials. Thus, late potentials were both common and evanescent in patients infected with human immunodeficiency virus.

Calcium and heart attacks. No evidence for increased risk.

Bolland and colleagues contrast the results of their meta-analysis with those of the women’s health initiative (WHI) randomised controlled trial of calcium/vitamin D supplementation with 254u2009000 subject years of follow-up.1 2 Cardiovascular events in the WHI study were pre-specified end points …

Statins for the Primary Prevention of Cardiovascular Events in Women with Elevated High-Sensitivity C-Reactive Protein or Dyslipidemia: Results from JUPITER and meta-analysis of women from primary prevention trials

Background nStatin therapy in women without cardiovascular disease (CVD) is controversial given insufficient evidence for benefit. We analyzed sex-specific outcomes in JUPITER and synthesized the results with prior trials.

Predictors of Heart Failure in Patients With Stable Coronary Artery DiseaseCLINICAL PERSPECTIVE: A PEACE Study

Background—Heart failure (HF) is a disease commonly associated with coronary artery disease. Most risk models for HF development have focused on patients with acute myocardial infarction. The Prevention of Events with Angiotensin-Converting Enzyme Inhibition population enabled the development of a risk model to predict HF in patients with stable coronary artery disease and preserved ejection fraction. Methods and Results—In the 8290, Prevention of Events with Angiotensin-Converting Enzyme Inhibition patients without preexisting HF, new-onset HF hospitalizations, and fatal HF were assessed over a median follow-up of 4.8 years. Covariates were evaluated and maintained in the Cox regression multivariable model using backward selection if P<0.05. A risk score was developed and converted to an integer-based scoring system. Among the Prevention of Events with Angiotensin-Converting Enzyme Inhibition population (age, 64±8; female, 18%; prior myocardial infarction, 55%), there were 268 cases of fatal and nonfatal HF. Twelve characteristics were associated with increased risk of HF along with several baseline medications, including older age, history of hypertension, and diabetes. Randomization to trandolapril independently reduced the risk of HF. There was no interaction between trandolapril treatment and other risk factors for HF. The risk score (range, 0 to 21) demonstrated excellent discriminatory power (c-statistic 0.80). Risk of HF ranged from 1.75% in patients with a risk score of 0% to 33% in patients with risk score ≥16. Conclusion—Among patients with stable coronary artery disease and preserved ejection fraction, traditional and newer factors were independently associated with increased risk of HF. Trandolopril decreased the risk of HF in these patients with preserved ejection fraction.