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.

Atherosclerosis and its clinical manifestations are widely prevalent throughout the world. Atherogenesis is highly complex and is modulated by numerous genetic and environmental risk factors. A large body of basic scientific and clinical research supports the conclusion that inflammation plays a significant role in atherogenesis along the entire continuum of its progression. Inflammation adversely impacts intravascular lipid handling and metabolism, resulting in the development of macrophage foam cells, fatty streaks and atheromatous plaque formation. Given the enormous human and economic cost of myocardial infarction, ischemic stroke, peripheral arterial disease and amputation, and premature death and disability, considerable effort is being committed to refining our ability to correctly identify patients at heightened risk for atherosclerotic vascular disease and acute cardiovascular events so that they can be treated earlier and more aggressively. Serum markers of inflammation have emerged as an important component of risk factor burden. Serum lipoprotein-associated phospholipase A2 (Lp-PLA2) potentiates intravascular inflammation and atherosclerosis. A variety of epidemiologic studies support the utility of Lp-PLA2 measurements for estimating and further refining cardiovascular disease risk. Drug therapies to inhibit Lp-PLA2 are in development and show considerable promise. In addition to substantially inhibiting Lp-PLA2, darapladib reduces the progression of the necrotic core volume of coronary artery atheromatous plaque.

Most apparently healthy, middle-aged women are classified as low-risk (10-year coronary heart disease [CHD] risk < 10%) via Framingham Risk Score (FRS). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an arterial-specific inflammatory enzyme implicated in the formation of vulnerable, rupture-prone plaque. Published studies suggest that elevated levels of this inflammatory marker identify individuals at high-risk for CHD who may not be identified by traditional risk factor assessment alone, and who may benefit from more aggressive treatment interventions. PURPOSE: The primary objective of this study was to determine the prevalence of elevated Lp-PLA2 in a population of FRS low-risk women. The secondary objective was to determine variables, which may be predictive of a high Lp-PLA2 level in this population. METHODS: Eighty women (52.8 ± 6.4 years) with low-risk for CHD per FRS had resting blood pressure, body mass index, waist circumference, LDL and HDL cholesterol, triglycerides, fasting blood glucose, physical activity status (measured using ActiGraph GT1M; ActiGraph, Pensacola, FL), CHD family history, menopausal status, and past or present use of hormone replacement therapy or oral contraceptives assessed. Both Lp-PLA2 mass and activity were measured using a commercially available, FDA approved enzyme-linked immunosorbent assay (ELISA) kit (PLACTM test; diaDexus, Inc., South San Francisco, CA). RESULTS: Ten women (13%) had high Lp-PLA2 mass (≥ 200 ng.dL-1) and 27 (34%) had high Lp-PLA2 activity (≥ 150nmol.mL-1.min-1). Logistical regression analyses found that only LDL was a significant predictor of both high Lp-PLA2 mass (p < 0.03) and activity (p < 0.01). LDL was significantly greater in the subgroups with high Lp-PLA2 mass (134 ± 14 vs. 99 ± 8 mg.dL-1; p < 0.03) and with high Lp-PLA2 activity (143 ± 6 vs. 107 ±3 mg.dL-1; p < 0.01). CONCLUSION: The current consensus panel recommendation calls for incorporating Lp-PLA2 testing in those at moderate risk for CHD. Based on the results of this study it is concluded that there is merit in testing for Lp-PLA2 in middle-aged women classified as low-risk for CHD by FRS, particularly in those with LDL > 130 mg.dL-1. Women identified with high Lp-PLA2 levels would be candidates for intensified treatment of risk factors, including an LDL goal of <100 mg.dL-1.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) is a novel inflammatory biomarker that is associated with increased cardiovascular disease risk independent of and additive to traditional risk factors. Lp-PLA(2) activity is correlated with the degree of inflammation in the atherosclerotic plaque. In human blood, approximately 80% of Lp-PLA(2) is associated with low-density lipoproteins (LDL). Thus, it is hypothesized that changes in Lp-PLA(2) should imitate the changes in the LDL cholesterol.OBJECTIVE: In this present study, we examined the efficacy of lifestyle intervention and combination lipid-lowering therapy on reducing the Lp-PLA(2) levels and determined the relationship between changes in LDL-C and Lp-PLA(2).METHODS: This retrospective chart review study includes two hundred forty eight patients (58% men and 42% women) who completed the life style intervention in combination with pharmacologic therapy for an average period of 10.5 months. Life style modification included diet and exercise counseling. Combination therapy included omega 3 fish oil (2000 mg/d), ex tended-re lease niacin (500-1000 mg/d), ezetimibe (10 mg/d), fenofibrate 160 mg/d and colesevelam HCI (1850 mg/d), as well as statins. The statins used were either simvastatin (20-40 mg/d) or rosuvastatin (5-20 mg/d). Sixty five percent (n = 161) received low to medium doses of simvastatin, whereas 35% (n = 87) received low to medium doses of rosuvastatin.RESULTS: The study revealed a 32.5% reduction in mean Lp-PLA(2) values (baseline 181.1 +/- 41.5 vs 122.1 +/- 28.1 ng/mL after treatment; P < .001). The change observed in LDL-C was 41%, (baseline 126.2 +/- 43 vs 73.9 +/- 37.7 mg/dL after treatment), which also was significant (P < .001). However, a Pearson correlation test analysis revealed only a weak positive association between changes in Lp-PLA(2) and LDL-C (r(2) = 0.052, P < .001).CONCLUSION: Lp-PLA(2) is reduced with the use of lifestyle counseling and combination lipid lowering therapy. Results also revealed that changes in Lp-PLA(2) maybe partially explained by the changes in LDL-C. (C) 2009 National Lipid Association. All rights reserved.

Coronary artery disease (CAD) is the leading cause of death and disability in the United States. 1 Heron M. Deaths: leading causes for 2004. Natl Vital Stat Rep. 2007; 56: 1-96 PubMed Google Scholar Although traditional risk factors are helpful in global risk assessment, often these population risk estimations lack the necessary precision when applied to an individual. 2 Sibley C. Blumenthal R.S. Bairey Merz C.N. Mosca L. Limitations of current cardiovascular disease risk assessment strategies in women. J Women Health. 2006; 15: 54-56 Crossref PubMed Scopus (50) Google Scholar Acknowledging the limitations of traditional risk factors to precisely assess cardiovascular risk among many persons, the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) recognizes the potential of bioinflammatory markers to more properly assess hidden cardiovascular risk as an adjunct to traditional risk factor assessment. 3 National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol education Program (NCEP) Expert Panel on detection, evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106 (II-30–II-31): 3143-3421 PubMed Google Scholar A newly developed risk-assessment tool referred to as the Reynolds Risk Score 4 Ridker P. Buring J. Rifai N. Cook N. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women. JAMA. 2007; 297: 611-619 Crossref PubMed Scopus (1435) Google Scholar was designed to used on apparently-healthy women without a history of diabetes mellitus to predict the risk of future heart attack, stroke, or other major heart disease in the next 10 years. The risk factors incorporated in this revised score include sex, current smoking status, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), and family history of premature heart disease.

Background: Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) mass is a novel inflammatory biomarker and independent predictor for cardiovascular disease. In human blood, Lp-PLA 2 is predominately associated with low-density lipoprotein (LDL). Thus, it is hypothesized that changes in Lp-PLA 2 should mirror changes in levels of LDL. To our knowledge, no studies exist which have examined the efficacy of lifestyle intervention and lipid drug therapy on reducing levels of Lp-PLA 2 while also determining the relationship between changes in LDL and Lp-PLA 2 . Therefore, the primary purpose of this study was to assess the ability of lifestyle and combination lipid drug therapy to reduce levels of Lp-PLA 2 among patients treated for mixed dyslipidemia. The secondary purpose was to examine the relationship between changes observed in Lp-PLA 2 and LDL cholesterol (LDL-C). Methods: Thirty dyslipidemic patients who received lifestyle intervention and combination lipid altering drug therapy for an average period of 6 months were included in these analyses (mean age=60.9, 40% with stable angiographically established CAD, 40% metabolic syndrome, 70% male). Lifestyle intervention included diet and exercise counseling. Drug therapy included omega-3 fish oil, extended release niacin, colesevelam HCl and a fixed combination of 10 mg ezetimibe and 40 mg simvastatin. Measures of Lp-PLA 2 were determined by an FDA approved ELISA assay (PLAC ™ test, diaDexus, Inc.), whereas LDL-C was calculated with the Friedewald equation using overnight fasting blood samples. Results: The study revealed a 34% reduction in median Lp-PLA 2 values (baseline 230.5 3 47.4 vs. post-treatment 151.0 ± 35.5 ng/mL; p 2 mass (R 2 =0.29; p Conclusion: Lp-PLA 2 mass is significantly reduced with the use of lifestyle and combination lipid lowering drug therapy. Changes in Lp-PLA 2 were only partially explained by the changes observed for LDL-C.