Baseline and On-Treatment High-Density Lipoprotein Cholesterol and the Risk of Cancer in Randomized Controlled Trials of Lipid-Altering Therapy

ObjectivesWe sought to examine the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of the development of cancer in large randomized controlled trials (RCTs) of lipid-altering interventions.BackgroundEpidemiologic data demonstrate an inverse relationship between serum total cholesterol levels and incident cancer. We recently reported that lower levels of low-density lipoprotein cholesterol are associated with a significantly higher risk of incident cancer in a meta-analysis of large RCTs of statin therapy. However, little is known about the relationship between HDL-C levels and cancer risk.MethodsA systematic MEDLINE search identified lipid intervention RCTs with ≥1,000 person-years of follow-up, providing baseline HDL-C levels and rates of incident cancer. Using random-effects meta-regressions, we evaluated the relationship between baseline HDL-C and incident cancer in each RCT arm.ResultsA total of 24 eligible RCTs were identified (28 pharmacologic intervention arms and 23 control arms), with 625,477 person-years of follow-up and 8,185 incident cancers. There was a significant inverse association between baseline HDL-C levels and the rate of incident cancer (p = 0.018). The inverse association persisted after adjusting for baseline low-density lipoprotein cholesterol, age, body mass index (BMI), diabetes, sex, and smoking status, such that for every 10-mg/dl increment in HDL-C, there was a 36% (95% confidence interval: 24% to 47%) relatively lower rate of the development of cancer (p < 0.001).ConclusionsThere is a significant inverse association between HDL-C and the risk of incident cancer that is independent of LDL-C, age, BMI, diabetes, sex, and smoking

Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer Insights From Large Randomized Statin Trials

ObjectivesWe sought to assess the relationship between the magnitude of low-density lipoprotein cholesterol (LDL-C) lowering and rates of elevated liver enzymes, rhabdomyolysis, and cancer.BackgroundAlthough it is often assumed that statin-associated adverse events are proportional to LDL-C reduction, that assumption has not been validated.MethodsAdverse events reported in large prospective randomized statin trials were evaluated. The relationship between LDL-C reduction and rates of elevated liver enzymes, rhabdomyolysis, and cancer per 100,000 person-years was assessed using weighted univariate regression.ResultsIn 23 statin treatment arms with 309,506 person-years of follow-up, there was no significant relationship between percent LDL-C lowering and rates of elevated liver enzymes (R2<0.001, p = 0.91) or rhabdomyolysis (R2= 0.05, p = 0.16). Similar results were obtained when absolute LDL-C reduction or achieved LDL-C levels were considered. In contrast, for any 10% LDL-C reduction, rates of elevated liver enzymes increased significantly with higher statin doses. Additional analyses demonstrated a significant inverse association between cancer incidence and achieved LDL-C levels (R2= 0.43, p = 0.009), whereas no such association was demonstrated with percent LDL-C reduction (R2= 0.09, p = 0.92) or absolute LDL-C reduction (R2= 0.05, p = 0.23).ConclusionsRisk of statin-associated elevated liver enzymes or rhabdomyolysis is not related to the magnitude of LDL-C lowering. However, the risk of cancer is significantly associated with lower achieved LDL-C levels. These findings suggest that drug- and dose-specific effects are more important determinants of liver and muscle toxicity than magnitude of LDL-C lowering. Furthermore, the cardiovascular benefits of low achieved levels of LDL-C may in part be offset by an increased risk of cancer

Inflammatory cytokines and atrial fibrillation: current and prospective views

Atrial fibrillation (AF) is the most common sustained arrhythmia and a challenging clinical problem encountered in daily clinical practice. There is an increasing body of evidence linking inflammation to a broad spectrum of cardiovascular conditions including AF. Historical evidence supports an association between AF and inflammation and is consistent with the association of AF with inflammatory conditions of the heart, such as myocarditis and pericarditis. AF has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. Increased plasma interleukin (IL)-6, C-reactive protein (CRP), and plasma viscosity support the existence of an inflammatory state among “typical” populations with chronic AF. These indexes of inflammation are related to the prothrombotic state and may be linked to the clinical characteristics of the patients (underlying vascular disease and comorbidities), rather than simply to the presence of AF itself. It has been suggested that inflammation may have a role in the development of atrial arrhythmias after cardiac surgery, and that a genetic predisposition to develop postoperative complications exists. Cytokines can have a prognostic significance; IL-6 levels, CRP, and other cytokines may have prognostic value in AF. Cytokine lowering therapies, statins, angiotensin converting enzyme inhibitors and other anti-inflammatory agents may have a role in the treatment of AF. The present article provides an overview of the evidence linking inflammatory cytokines to AF and their therapeutic and prognostic implications

Commotio Cordis

Sudden arrhythmic death as a result of a blunt chest wall blow has been termed Commotio Cordis (CC). CC is being reported with increasing frequency with more than 180 cases now described in the United States Commotio Cordis Registry. The clinical spectrum is diverse; however young athletes tend to be most at risk, with victims commonly being struck by projectiles regarded as standard implements of the sport. Sudden death is instantaneous and victims are most often found in ventricular fibrillation (VF). Chest blows are not of sufficient magnitude to cause any significant damage to overlying thoracic structures and autopsy is notable for the absence of any structural cardiac injury. Development of an experimental model has allowed for substantial insights into the underlying mechanisms of sudden death. In anesthetized juvenile swine, induction of VF is instantaneous following chest impacts that occur during a vulnerable window before the T wave peak. Other critical variables, including the impact velocity and location, and the hardness of the impact object have also been identified. Rapid left ventricular pressure rise following chest impact likely results in activation of ion channels via mechano-electric coupling. The generation of inward current through mechano-sensitive ion channels results in augmentation of repolarization and non-uniform myocardial activation, and is the cause of premature ventricular depolarizations that are triggers of VF in CC. Currently available chest protectors commonly used in sport are not adequately designed to prevent CC. The development of more effective chest protectors and the widespread availability of automated external defibrillators at youth sporting events could improve the safety of young athletes

Case-finding of chronic obstructive pulmonary disease with questionnaire, peak flow measurements and spirometry : a cross-sectional study

Peer reviewedPublisher PD

The “obesity paradox” in patients with atrial fibrillation:Insights from the Gulf SAFE registry

BACKGROUND: The prognostic impact of obesity on patients with atrial fibrillation (AF) remains under-evaluated and controversial. METHODS: Patients with AF from the Gulf Survey of Atrial Fibrillation Events (Gulf SAFE) registry were included, who were recruited from six countries in the Middle East Gulf region and followed for 12 months. A multivariable model was established to investigate the association of obesity with clinical outcomes, including stroke or systemic embolism (SE), bleeding, admission for heart failure (HF) or AF, all-cause mortality, and a composite outcome. Restricted cubic splines were depicted to illustrate the relationship between body mass index (BMI) and outcomes. Sensitivity analysis was also conducted. RESULTS: A total of 1,804 patients with AF and recorded BMI entered the final analysis (mean age 56.2 ± 16.1 years, 47.0% female); 559 (31.0%) were obese (BMI over 30 kg/m(2)). In multivariable analysis, obesity was associated with reduced risks of stroke/systematic embolism [adjusted odds ratio (aOR) 0.40, 95% confidence interval (CI), 0.18–0.89], bleeding [aOR 0.44, 95%CI, 0.26–0.74], HF admission (aOR 0.61, 95%CI, 0.41–0.90) and the composite outcome (aOR 0.65, 95%CI, 0.50–0.84). As a continuous variable, higher BMI was associated with lower risks for stroke/SE, bleeding, HF admission, all-cause mortality, and the composite outcome as demonstrated by the accumulated incidence of events and restricted cubic splines. This “protective effect” of obesity was more prominent in some subgroups of patients. CONCLUSION: Among patients with AF, obesity and higher BMI were associated with a more favorable prognosis in the Gulf SAFE registry. The underlying mechanisms for this obesity “paradox” merit further exploration

Polyvascular Disease in Patients Presenting with Acute Coronary Syndrome: Its Predictors and Outcomes

We evaluated prevalence and clinical outcome of polyvascular disease (PolyVD) in patients presenting with acute coronary syndrome (ACS). Data for 7689 consecutive ACS patients were collected from the 2nd Gulf Registry of Acute Coronary Events between October 2008 and June 2009. Patients were divided into 2 groups (ACS with versus without PolyVD). All-cause mortality was assessed at 1 and 12 months. Patients with PolyVD were older and more likely to have cardiovascular risk factors. On presentation, those patients were more likely to have atypical angina, high resting heart rate, high Killip class, and GRACE risk scoring. They were less likely to receive evidence-based therapies. Diabetes mellitus, renal failure, and hypertension were independent predictors for presence of PolyVD. PolyVD was associated with worse in-hospital outcomes (except for major bleedings) and all-cause mortality even after adjusting for baseline covariates. Great efforts should be directed toward primary and secondary preventive measures

Demystifying Smoker's Paradox: A Propensity Score-Weighted Analysis in Patients Hospitalized With Acute Heart Failure.

Background Smoker's paradox has been observed with several vascular disorders, yet there are limited data in patients with acute heart failure (HF). We examined the effects of smoking in patients with acute HF using data from a large multicenter registry. The objective was to determine if the design and analytic approach could explain the smoker's paradox in acute HF mortality. Methods and Results The data were sourced from the acute HF registry (Gulf CARE [Gulf Acute Heart Failure Registry]), a multicenter registry that recruited patients over 10 months admitted with a diagnosis of acute HF from 47 hospitals in 7 Middle Eastern countries. The association between smoking and mortality (in hospital) was examined using covariate adjustment, making use of mortality risk factors. A parallel analysis was performed using covariate balancing through propensity scores. Of 5005 patients hospitalized with acute HF, 1103 (22%) were current smokers. The in-hospital mortality rates were significantly lower in current smoker's before (odds ratio, 0.71; 95% CI, 0.52-0.96) and more so after (odds ratio, 0.47; 95% CI, 0.31-0.70) covariate adjustment. With the propensity score-derived covariate balance, the smoking effect became much less certain (odds ratio, 0.63; 95% CI, 0.36-1.11). Conclusions The current study illustrates the fact that the smoker's paradox is likely to be a result of residual confounding as covariate adjustment may not resolve this if there are many competing prognostic confounders. In this situation, propensity score methods for covariate balancing seem preferable. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01467973.Gulf CARE (Gulf Acute Heart Failure Registry) is an investigator- initiated study conducted under the auspices of the Gulf Heart Association and funded by Servier, Paris, France; and (for centers in Saudi Arabia), by the Saudi Heart Association (The Deanship of Scientific Research at King Saud University, Riyadh, Saudi Arabia [research group number: RG -1436- 013]). This does not alter our adherence to policies on sharing data and materials; and the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The publication of this article was funded by the Qatar National Library