AIMSWhile suboptimal adherence to statin medication has been quantified in real-world patient settings, a better understanding of its impact is needed, particularly with respect to distinct problems of medication taking. Our aim was to synthesize current evidence on the impacts of statin adherence, discontinuation and persistence on cardiovascular disease and mortality outcomes. METHODSWe conducted a systematic review of peer-reviewed studies using a mapped search of Medline, Embase and International Pharmaceutical Abstracts databases. Observational studies that met the following criteria were included: defined patient population; statin adherence exposure; defined study outcome [i.e. cardiovascular disease (CVD), mortality]; and reporting of statin-specific results. RESULTSOverall, 28 studies were included, with 19 studies evaluating outcomes associated with statin adherence, six with statin discontinuation and three with statin persistence. Among adherence studies, the proportion of days covered was the most widely used measure, with the majority of studies reporting increased risk of CVD (statistically significant risk estimates ranging from 1.22 to 5.26) and mortality (statistically significant risk estimates ranging from 1.25 to 2.54) among non-adherent individuals. There was greater methodological variability in discontinuation and persistence studies. However, findings of increased CVD (statistically significant risk estimates ranging from 1.22 to 1.67) and mortality (statistically significant risk estimates ranging from 1.79 to 5.00) among nonpersistent individuals were also consistently reported. CONCLUSIONSObservational studies consistently report an increased risk of adverse outcomes associated with poor statin adherence. These findings have important implications for patients and physicians and emphasize the importance of monitoring and encouraging adherence to statin therapy.

Purpose-To evaluate the impact of serum uric acid levels on the future risk of developing type 2 diabetes independent of other factors.Methods-We used prospective data from the Framingham Heart Study original (n=4,883) and offspring (n=4,292) cohorts to examine the association between serum uric acid levels and the incidence of diabetes. We used Cox proportional hazards models to estimate the relative risk (RR) of incident diabetes adjusting for age, sex, physical activity, alcohol consumption, smoking, hypertension, body mass index, and blood levels of glucose, cholesterol, creatinine, and triglycerides.Results-We identified 641 incident cases of diabetes in the original cohort and 497 cases in the offspring cohort. The incidence rates of diabetes per 1000 person-years for serum uric acid levels <5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9 and ≥8.0 mg/dL were 3. 3, 6.1, 8.7, 11.5, and 15.9 in the original cohort, and 2. 9, 5.0, 6.6, 8.7, 10.9 in the offspring cohort, respectively (P-values for trends <0.001). Multivariable RRs per mg/dL increase in serum uric acid levels were 1.20 (95% CI, 1.11 to 1.28) for the original cohort and 1.15 (95% CI, 1.06 to 1.23) for the offspring cohort.Conclusions-These prospective data from two generations of the Framingham Heart Study provide evidence that individuals with higher serum uric acid, including younger adults, are at a higher future risk of type 2 diabetes independent of other known risk factors. These data expand on cross-sectional associations between hyperuricemia and the metabolic syndrome, and extend the link to the future risk of type 2 diabetes. © 2010 Elsevier Inc. All rights reserved.Corresponding Author: Hyon Choi, MD, DrPH, Section of Rheumatology and the Clinical Epidemiology Unit, Boston University of School of Medicine, 650 Albany Street, Suite 200, Boston, MA 02118, Tel: +1 617-638-5490; Fax: +1 617-638-5239, hchoius@bu.edu. Author Contributions: All authors had access to the data and were involved in drafting the article and revising it critically for important intellectual content.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The prevalence of diabetes in the U.S (2007) was estimated to be 10.7% (23.5 million) among adults aged 20 years or older and 23.1% (12.2 million) among those aged 60 years and older. 1 Hyperuricemia, the precursor of gout, is strongly associated with insulin resistance syndrome, an established risk factor for type 2 diabetes. 2,3 This link may be translated into an independent association between hyperuricemia and the future risk of type 2 diabetes, but little prospective data on the topi...

Objective. Despite the recent doubling of the incidence of gout among women and its substantial prevalence particularly in the aging female population, the risk factors for gout among women remain unknown. We undertook this study to evaluate purported risk factors for incident gout among women and to compare them with those among men.Methods. Using prospective data from the Framingham Heart Study, we examined over a 52-year period ) the relationship between purported risk factors and the incidence of gout in 2,476 women and 1,951 men.Results. We documented 304 incident cases of gout, 104 of them among women. The incidence rates of gout for women per 1,000 person-years according to serum uric acid levels of <5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9, and >8.0 mg/dl were 0.8, 2.5, 4.2, 13.1, and 27.3, respectively (P for trend < 0.0001). The magnitude of this association was lower than that among men (P for interaction ‫؍‬ 0.0002). Multivariate relative risks conferred by increasing age (per 5 years), obesity (body mass index >30 kg/m 2 ), alcohol intake (>7 ounces of pure alcohol/week), hypertension, and diuretic use were 1.24, 2.74, 3.10, 1.82, and 2.39, respectively (all P < 0.05), for women.Conclusion. These prospective data with longterm followup provide evidence that higher levels of serum uric acid increase the risk of gout in a graded manner among women, but the rate of increase is lower than that among men. Increasing age, obesity, alcohol consumption, hypertension, and diuretic use were associated with the risk of incident gout among women.Gout, a common and excruciatingly painful inflammatory arthritis (1), has historically been considered a male disease, and most gout research has focused on men (2-9). However, growing evidence suggests a substantial disease burden of gout among older women, whose representation in the general population has grown with increasing longevity. The prevalence of self-reported physician-diagnosed gout based on the Third National Health and Nutrition Examination Survey (NHANES-III) was 3.5% in women ages 60-69 years, 4.6% in women ages 70-79 years, and 5.6% in women ages Ն80 years (10). The incidence of gout has doubled among women over the past 20 years, according to the Rochester Epidemiology project study (11). Despite this substantial and increasing disease burden, the risk factors for gout among women remain unknown.Given the significant role of estrogen in serum uric acid levels as well as the substantial sex difference in the incidence of gout and perhaps in uric acid metabolism (12), extrapolation of data on the risk factors for gout from men to women should be done with caution. The serum uric acid level, which is the most prominent predictor and precursor of gout, has been prospectively studied in relation to the risk of incident gout among men (2), but no corresponding data among women are

These findings from men with a high cardiovascular risk profile suggest that men with gout are at a higher future risk of type 2 diabetes independent of other known risk factors. These data expand on well-established, cross-sectional associations between hyperuricaemia, gout and the metabolic syndrome, and extend the link to the future risk of type 2 diabetes.