Background: Statins may reduce cardiovascular (CV) morbidity in patients with mild-to-moderate elevations in liver enzyme levels. This post-hoc analysis of the IDEAL study compared intensive versus moderate statin therapy for the prevention of CV events in coronary heart disease patients with normal and elevated baseline levels of serum alanine aminotransferase (ALT).Methods: Cox regression analysis was used to investigate the effect of atorvastatin 80 mg/day versus simvastatin 20-40 mg/day on the risk of IDEAL study end points in patients with normal baseline ALT (defined as ALT < ULN [upper limit of normal]) versus elevated baseline ALT (ALT >= ULN).Results: Of 8863 IDEAL patients with non-missing baseline ALT values, 7782 (87.8%) had an ALT < ULN and 1081 (12.2%) had an ALT >= ULN. In patients with elevated baseline ALT, major CV event rates were 11.5% for simvastatin and 6.5% for atorvastatin, indicating a significant risk reduction with intensive statin therapy (hazard ratio, 0.556; 95% confidence interval, 0.367-0.842; p = 0.0056). Significant heterogeneity of treatment effect was observed for major CV events, cerebrovascular events, and major coronary events, with a trend towards treatment difference for the other outcomes, indicating a greater benefit with atorvastatin in the elevated ALT group.Conclusions: The CV benefit of intensive lipid lowering with atorvastatin compared with a more moderate regimen with simvastatin was generally greater in patients with mildly-to-moderately elevated baseline ALT than patients with normal baseline ALT. Moderate elevations in liver enzyme levels should not present a barrier to prescribing statins, even at higher doses, in high-risk patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND:The risk factors associated with, and the incidence of systemic embolism in patients with atrial fibrillation (AF) are poorly understood.OBJECTIVES:We studied the association between AF and upper limb thromboembolectomy involving brachial, ulnar or radial artery in a national cohort study that included all individuals aged 40-99 years with incident AF.METHODS:Data were retrieved from the Danish National Vascular Registry, the National Registry of Patients, the Danish Civil Registration System and Statistics Denmark.RESULTS:In total, 131,476 patients (68,042 men and 63,434 women) with AF without previous thromboembolectomy in the upper limb were registered. In the study cohort, 130 men underwent upper limb thromboembolectomy over 220,890 person-years of observation, whilst 275 women underwent thromboembolectomy over 197,777 patient-years. The incidence per 100,000 person-years was 58.9 (95% CI, 49.2-69.8) for men and 139.1 (95% CI, 123.1-156.5) for women. The relative risk of thromboembolectomy among patients with AF compared to the background population was 7.5 (95% CI, 6.3-8.9) for men, and 9.3 (95% CI, 8.3-10.5) for women. Women with AF had a relative thromboembolectomy risk of 1.8 (95% CI, 1.5-2.3) compared to men with AF. Among patients with AF, history of hypertension (HR 2.2-2.9), myocardial infarction (HR 2.9-3.9), heart failure (HR 1.6-1.9) and stroke (HR 2.2-3.8) were significantly associated with increased risk of thromboembolectomy in both men and women.CONCLUSIONS:AF substantially increases the risk of upper limb thromboembolectomy. This risk is higher with increasing age, female gender, and associated with hypertension, myocardial infarction, heart failure and stroke.

The aim of this study was to define optimal cut points for the Alcohol Use Disorders Identification Test (AUDIT) and its abbreviated versions (AUDIT-C, AUDIT-QF, and AUDIT-3), and to evaluate how effectively these questionnaires detect heavy drinking in the general population.The study population consisted of a sub-sample of the National FINRISK Study. A stratified random sample of 3216 Finns, aged 25–64, was invited to a health check. Of these, 1851 (57.6%) completed the AUDIT and participated in person in the Timeline Followback (TLFB) interview regarding their alcohol consumption. The TLFB-based definition of heavy drinking was used as a primary gold standard (for males ≥16 standard drinks average in a week or ≥7 drinks at least once a month; for females, respectively, ≥10 and ≥5 drinks). Areas under receiving operating characteristics curves (AUROCs), sensitivities and specificities were used to compare the performance of the tests.The AUDIT and its abbreviated versions are valid for detecting heavy drinking also in a general population sample. However, performance seems to vary between the different versions and accuracy of each test is achieved only by using tailored cut points according to gender. The AUDIT and AUDIT-C are effective for both males and females. The optimal cut points for males were found to be ≥7 or 8 for AUDIT and ≥6 for AUDIT-C. Among females the optimal cut points were found to be ≥5 for AUDIT and ≥4 for AUDIT-C. The study also indicates that AUDIT-QF among females and AUDIT-3 among males are relatively effective. The cut points for detecting all heavy drinkers (including binge drinkers without exceeding weekly thresholds) were lower than for detecting heavy drinkers excluding those who are only binge drinkers.

ObjectivesWe investigated the incidence of thrombo-embolectomy in upper-limb and prognosis with respect to arm amputation, stroke and death.MethodsWe performed a national cohort study of individuals, aged 40–99 years, and undergoing first-time thrombo-embolectomy in the brachial, ulnar or radial artery in Denmark from 1990 to 2002. The data were retrieved from the National Vascular Registry and from the National Registry of Patients and the Civil Registration System. Patients were followed until 2006 to ascertain the occurrence of amputation and stroke and until 2007 with respect to death.ResultsIn total, 1377 incident cases of thrombo-embolectomy were registered, comprising 504 (36.6%) males with a mean age of 72.0 (standard deviation (SD) 12.4) years and 873 (63.4%) females with a mean age of 77.2 (SD 11.7) years. Incidence was 3.3 (95% confidence interval (CI): 3.1–3.7) for males and 5.2 (95% CI: 4.9–5.6) for females per 100000 person-years. After thrombo-embolectomy, upper-limb amputation was performed in 11 (incidence 2.2%; 95% CI: 1.2–3.4) males and 31 (3.6%; 95% CI: 2.5–4.9) females. Age- and sex-specific risk of stroke was 2–16 times higher, and risk of death 3–11 times higher, than in the general population.ConclusionsUpper-limb thrombo-embolectomy is associated with an increased risk of limb amputation, stroke and death.

Abstract.  Holme I, Fayyad R, Faergeman O, Kastelein JJP, Olsson AG, Tikkanen MJ, Larsen ML, Lindahl C, Holdaas H, Pedersen TR, On behalf of the Incremental Decrease in End Points Through Aggressive Lipid Lowering Study Group (Centre of Preventive Medicine, Oslo, Norway; Århus University Hospital, Århus, Denmark; Academic Hospital Amsterdam, Amsterdam, The Netherlands; University Hospital, Linköping, Sweden; Helsinki University Central Hospital, Helsinki, Finland; Oslo University Hospital, Rikshospitalet, Oslo, Norway; Pfizer Sweden, Sollentuna, Sweden; and Pfizer Inc., New York, NY, USA). Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: Results from the IDEAL trial. J Intern Med 2010; 267:567–575.

Background: Patients at high risk of cardiovascular disease frequently fail to reach recommended low-density lipoprotein cholesterol (LDL-C) goals, partly because statin doses are not titrated to optimal effect. The ECLIPSE study was designed to compare the efficacy and safety of force-titrated treatment with rosuvastatin (10–40 mg) with that of atorvastatin (10–80 mg) in high-risk patients with hypercholesterolemia. Methods: In this 24-week, open-label, randomized, multinational, parallel-group study, 1,036 patients were randomized to rosuvastatin (n = 522) or atorvastatin (n = 514). Results: At all time points, a significantly greater percentage of patients on rosuvastatin treatment achieved the NCEP ATP III LDL-C goal of <100 mg/dl (2.5 mmol/l), the 2003 European LDL-C target of <2.5 or 3.0 mmol/l (100 or 115 mg/dl) and the LDL-C goal of <70 mg/dl (1.8 mmol/l), a goal suggested for very high-risk patients (p < 0.001 for all). Rosuvastatin also achieved significantly greater improvements in components of the atherogenic lipid profile versus atorvastatin. Both treatments were well tolerated. Conclusion: Rosuvastatin titrated across its recommended dose range provides a more favorable effect on lipoprotein variables than atorvastatin, enabling more high-risk patients to achieve recommended LDL-C goals.

High-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels are inversely associated with adverse cardiovascular outcomes. Associations between these HDL-C–related measurements and coronary plaque progression have not been studied. We performed a retrospective analysis of 2,566 statin-treated patients with angiographic coronary artery disease who underwent serial evaluation of atheroma burden with intravascular ultrasound. Relations between achieved levels of HDL-related measurements with clinical characteristics and changes in plaque burden were determined. A strong correlation between HDL-C and apoA-I (r = 0.80, p <0.001) was observed. HDL-C, apoA-I, and the HDL-C:apoA-I ratio demonstrated negative correlations with the change in percent atheroma volume and total atheroma volume (all p ≤0.001). Increasing levels of achieved HDL-C:apoA-I (p = 0.04), but not HDL-C (p = 0.18) or apoA-I (p = 0.67), were associated with less progression of percent atheroma volume. Similar results were seen for change in total atheroma volume, with less progression seen with increased HDL-C:apoA-I (p = 0.002) but not with increases in HDL-C (p = 0.09) or apoA-I (p = 0.19). In conclusion, increasing levels of HDL-C:apoA-I associated with less progression of coronary atherosclerosis. This suggests that interventions increasing the cholesterol content of HDL particles may be of cardiovascular benefit.

Examination of low-density lipoprotein (LDL) receptor gene, its promoter, and most of exon-intron boundaries from 74 probands with familial hypercholesterolemia (FH) of St. Petersburg revealed 34 mutations and 8 widely spread polymorphisms at this locus. Only four mutations were considered neutral, while the other 30 are likely to cause familial hypercholesterolemia (FH). Mutations in the LDL receptor gene, causing the disease, were identified in 41 (55%) out of 74 families with FH. Mutation R3500Q in apolipoprotein B (APOB) gene was not detected in all probands. Therefore in the families lacking mutations hypercholesterolemia was caused by mutations in the introns of the LDL receptor gene or by other genetic factors. Nineteen mutations causing disease progression were described in St. Petersburg for the first time, while 18 of them are specific for Russia. Among Ashkenazi Jews, predominant mutation G197del was detected in 30% (7 out of 22) of patients with FH. In the Slavic population of St. Petersburg, no predominant mutations were detected. Only five mutations were identified in two Slavic families, while 24 were found in unique families. These data are indicative of the lack of a strong founder effect for FH in the St. Petersburg population.