Ishak A. Mansi

Association of Statin Use With Cataracts: A Propensity Score–Matched Analysis

IMPORTANCE Cataracts are a main cause of low vision; with the growing elderly population, the incidence of cataracts is likely to increase. Investigators have previously hypothesized that statin antioxidant effects may slow the natural aging process of the lens. OBJECTIVE To compare the risks for development of cataracts between statin users and nonusers. DESIGN A propensity score-matched cohort analysis using retrospective data from October 1, 2003, to March 1, 2010. A propensity score-matched cohort of statin users and nonusers was created using 44 variables. SETTING Database of a military health care system. PARTICIPANTS Based on medication fills during fiscal year 2005, patients were divided into 2 groups: (1) statin users (received at least a 90-day supply of statin) and (2) nonusers (never received a statin throughout the study). Among 46,249 patients meeting study criteria, we identified 13,626 statin users and 32,623 nonusers. EXPOSURE Use of statin therapy for more than 90 days. MAIN OUTCOMES AND MEASURES Primary analysis examined the risks for cataract in the propensity score-matched cohort. Secondary analyses examined the risks for cataract in patients with no comorbidities according to the Charlson Comorbidity Index (patients with no Charlson comorbidity). A sensitivity analysis was conducted to repeat the secondary analysis in patients taking statins for durations of 2, 4, and 6 years. RESULTS For our primary analysis, we matched 6972 pairs of statin users and nonusers. The risk for cataract was higher among statin users in comparison with nonusers in the propensity score-matched cohort (odds ratio, 1.09; 95% CI, 1.02-1.17). In secondary analyses, after adjusting for identified confounders, the incidence of cataract was higher in statin users in comparison with nonusers (odds ratio, 1.27; 95% CI, 1.15-1.40). Sensitivity analysis confirmed this relationship. CONCLUSIONS AND RELEVANCE The risk for cataract is increased among statin users as compared with nonusers. The risk-benefit ratio of statin use, specifically for primary prevention, should be carefully weighed, and further studies are warranted.

The controversy of a wider statin utilization: why?

Introduction: Several medical journals published viewpoints and counter-viewpoints supporting or opposing a wider utilization of statins for primary prevention. The objective of this article is not to weigh in the benefits versus risks of statin use, but to discuss various aspects of this controversy. Areas covered: This review discusses the challenges in examining the pleotropic effects/adverse events of statins. It also discusses the pitfalls in assessment of adverse events in randomized controlled trials and observational studies. Expert opinion: The challenges in solving this controversy include that the pleotropic effect of statins results in an extremely wide spectrum of reported benefits or adverse events, the reported harms/benefits are contradictory, there is basic research ground supporting both sides of the controversy, it is difficult to separate if adverse events are due to statins or due to lower cholesterol, and that there is a lack of standardized definition of statin-associated adverse events and their methods of ascertainment. Both randomized controlled trials and observational studies have pitfalls and caveats in assessment of adverse events. Understanding the points of debate is of paramount significance to enable clinicians to individualize patient care.

Statin Use and the Risk of Kidney Disease With Long-Term Follow-Up (8.4-Year Study).

Few studies have examined long-term effects of statin therapy on kidney diseases. The objective of this study was to determine the association of statin use with incidence of acute and chronic kidney diseases after prolonged follow-up. In this retrospective cohort study, we analyzed data from the San Antonio area military health care system from October 2003 through March 2012. Statin users were propensity score matched to nonusers using 82 baseline characteristics including demographics, co-morbidities, medications, and health care utilization. Study outcomes were acute kidney injury, chronic kidney disease (CKD), and nephritis/nephrosis/renal sclerosis. Of the 43,438 subjects included, we propensity score matched 6,342 statin users with 6,342 nonusers. Statin users had greater odds of acute kidney injury (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.14 to 1.48), CKD (OR 1.36, 95% CI 1.22 to 1.52), and nephritis/nephrosis/renal sclerosis (OR 1.35, 95% CI 1.05 to 1.73). In a subset of patients without co-morbidities, the association of statin use with CKD remained significant (OR 1.53, 95% CI 1.27 to 1.85). In a secondary analysis, adjusting for diseases/conditions that developed during follow-up weakened this association. In conclusion, statin use is associated with increased incidence of acute and chronic kidney disease. These findings are cautionary and suggest that long-term effects of statins in real-life patients may differ from shorter term effects in selected clinical trial populations.

Psychologic Disorders and Statin Use: A Propensity Score-Matched Analysis

To evaluate the association between statin therapy and the risk of psychologic disorders including schizophrenia, psychosis, major depression, and bipolar disorder in a military population.

Incidence of Musculoskeletal and Neoplastic Diseases in Patients on Statin Therapy: Results of a Retrospective Cohort Analysis

Background:Because of their beneficial cardiovascular effects, several studies have recently advocated starting statins at a young age for primary prevention. However, some reports suggest that statin therapy may be associated with an increased incidence of musculoskeletal and neoplastic diseases. This study was conducted to investigate the incidence of various musculoskeletal and neoplastic diseases in statin users and nonusers. Methods:A retrospective cohort study of patients in the San Antonio Military Multi-Service Market during the period from October 1, 2003, to March 5, 2010, was conducted. The International Classification of Diseases, 9th edition, diagnosis codes between 2 cohort groups—statin users and nonusers—were compared. Statin users were those patients with at least one 3-month prescription for a statin in the fiscal year 2004. Nonusers were those patients who received a prescription—but not a statin—during the period of the study. Both groups were assessed for the development of musculoskeletal and neoplastic diseases in the following 4-year period (October 1, 2004, to September 30, 2009). Results:A total of 92,360 patients were identified: 12,980 statin users and 45,997 nonusers. After adjusting for age, sex and Charlson comorbidity index, statin users had significantly higher rates of osteoarthritis and arthropathy (odds ratio: 1.26; 95% confidence interval: 1.19–1.33), and dorsopathies, rheumatism and chondropathies (odds ratio: 1.20; 95% confidence interval: 1.12–1.27). Conclusions:In this retrospective analysis, statin use was associated with an increased incidence of musculoskeletal diseases, including arthropathy. Further studies are needed to provide physicians and their patients with adequate information regarding statin therapy, particularly if recommended for primary prevention in younger populations.

Association of myocardial bridge and Takotsubo cardiomyopathy: a case report and literature review.

A woman presented with chest pain following emotional stress. Investigations showed acute ST-segment elevation, myocardial infarction, and elevated serum troponin. Emergency heart catheterization showed left anterior descending artery myocardial bridging, apical ballooning consistent with takotsubo cardiomyopathy (TTC), and decreased ejection fraction. Two days later, echocardiogram demonstrated near normalization of ventricular function.The etiology of TTC is not known but may include a stress-related surge of catecholamines or epicardial coronary spasm. Other case series reported an association of myocardial bridge and TTC. Catecholamines surge during stress might contribute to both diseases resulting in an apparent association; alternatively, a symptomatic myocardial bridge may be a contributing factor in worsening TTC.

Statin Adverse Events in Primary Prevention: Between Randomized Trials and Observational Studies

Abstract:Considerable debate exists regarding who might benefit from statins for primary prevention. Statins have wide pleotropic effects, which contribute to their efficacy in lowering cardiovascular disease but may also result in adverse events (AEs). Caveats in identifying AEs in randomized controlled trials (RCTs) include the lack of a standardized definition of statin-associated AEs, the differences in properties of different statins, the selectivity of RCTs in choosing their participants, the presence of high rate of nonadherence/withdrawal from trials and other concerns related to study design and conflict of interest. Caveats in identifying or overestimating AEs in observational studies include failure to identify baseline confounders, ascertainment bias, confounding by indication and healthy user bias. Statin use in observational studies may be a surrogate marker for higher socioeconomic standards, access to health care or use of other preventive services. Integrating evidence from both RCTs and observational studies is of paramount importance for appropriate patient-centered decision.

Non-High-Density Lipoprotein Cholesterol in Patients With Metabolic Syndrome

Background Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that includes hypertriglyceridemia. Although low-density lipoprotein (LDL) cholesterol is the critical therapeutic target in patients with coronary artery disease, LDL cannot be calculated in those with excessive hypertriglyceridemia. Non-high-density lipoprotein (HDL) does not require LDL for calculation and may be an alternative therapeutic target in MS. The purpose of this study was to determine non-HDL cholesterol in relation to other lipid components and comorbidities in MS patients. Methods A cross-sectional chart review on 928 public hospital patients was performed. Results Metabolic syndrome was present in 53% of all patients. Among those with MS, 87% had triglyceride level of greater than 150 mg/dL, 85% had low HDL, 71% had LDL of greater than 100 mg/dL, and 74% had non-HDL of greater than 130 mg/dL. The level of non-HDL cholesterol, but not total cholesterol or LDL cholesterol, was significantly higher (P < 0.05) and less at goal (P < 0.0001) in patients with MS. Diagnoses of coronary artery disease, hypertension, obesity, dyslipidemia, and diabetes were significantly more prevalent in MS patients (P < 0.0001). Conclusion Compared with those without MS, non-HDL level was significantly higher and undertargeted in patients with MS, in parallel with significantly higher prevalence of comorbidities.

The effect of statin therapy on the incidence of infections: A retrospective cohort analysis

Background:Statins have been postulated to prevent infection through immunomodulatory effects. Objectives:To compare the incidence of infections in statin users to that in nonusers within the same health care system. Methods:This was a retrospective cohort study of patients enrolled as Tricare Prime or Plus in the San Antonio military multimarket. Statin users were patients who received a statin for at least 3 months between October 1, 2004 and September 30, 2005. Nonusers were patients who did not receive a statin within the study period (October 1, 2003-September 30, 2009). Inpatient and outpatient International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes were used to determine the incidence of infections during the follow-up period (October 1, 2005-September 30, 2009) via multivariable regression analysis and time to infection via Cox regression analysis. Results:Of 45,247 patients who met the study criteria, 12,981 (29%) were statin users and 32,266 were nonusers. After adjustments for age, gender, Charlson Comorbidity Score, tobacco use, alcohol abuse/dependence, health care utilization and use of specific medication classes, statin use was associated with an increased incidence of common infections (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.06-1.19) but not influenza or fungal infections (OR: 1.06, 95% CI: 0.80-1.39; OR: 0.97; 95% CI: 0.91-1.04, respectively). Time-to-first infection was similar in statin users and nonusers in all infection categories examined. Conclusions:Statin use was associated with an increased incidence of common infections but not influenza or fungal infections. This study does not support a protective role of statins in infection prevention; however, the influence of potential confounders cannot be excluded.

Statin therapy and gastrointestinal hemorrhage: A retrospective cohort study with propensity score-matching

Whereas some studies suggest that statins exert a gastroprotective effect against gastrointestinal hemorrhage, others report that statin use is associated with increased risk of gastrointestinal hemorrhage. Aim of report: To investigate the risk of gastrointestinal hemorrhage among statin‐users compared with non‐users.