Racial differences in the burden of coronary artery calcium and carotid intima media thickness between Blacks and Whites.

BACKGROUND: Identification of racial differences in the burden and correlates of carotid intima media thickness (CIMT) and coronary artery calcium (CAC) may provide the basis for the development of race-specific cardiovascular disease (CVD) risk prediction algorithms. METHODS: In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, CIMT was measured by carotid ultrasonography in 792 individuals (35 % Black). CIMT >1 mm was considered significant. CAC was quantified by electron beam computed tomography in 776 individuals (46 % Black). CAC was considered significant if the Agatston score was >100. Cross-sectional associations between race, CIMT and CAC were assessed using logistic regression models. RESULTS: Blacks had greater CIMT (mean difference 0.033 mm, 95 % CI 0.005-0.06 mm; p = 0.02) and 1.5-fold (95 % CI 1.0-2.3) higher odds of having significant CIMT than Whites. Blacks had less CAC than Whites (mean Agatston score difference 66, [11-122]; p = 0.02) and 50 % lower odds of a significant CAC score compared with Whites (0.5 [0.3-0.7]). These associations were virtually unchanged after adjustment for CVD risk factors. Of the novel CVD risk markers assessed, small-dense low-density lipoprotein was independently associated with increased odds of significant CIMT, with the association being similar among Blacks and Whites (odds ratio [95 % CI]: 1.7 [1.2-2.5] and 1.4 [1.0-1.8] per 1-SD higher level, respectively). Interleukin-6 was significantly associated with CAC among Blacks (1.4 [1.0-2.0]). CONCLUSION: Black race is independently associated with greater CIMT but less CAC than White race. CVD risk stratification strategies that incorporate these measures of subclinical atherosclerosis should consider race-specific algorithms.

Hepatitis C virus treatment and survival in patients with hepatitis C and human immunodeficiency virus co-infection and baseline anaemia.

The impact of pretreatment anaemia on survival in individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection is not known. Moreover, HCV treatment is offered less frequently to individuals with anaemia, due to haematological side effects of the treatment regimen. This study aimed to determine the effect of HCV treatment on survival among HCV/HIV co-infected individuals with pretreatment anaemia using the Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES). Individuals with HCV/HIV co-infection were included in current analyses. Participants were considered treated if they were prescribed ≥ 4 weeks of HCV treatment. All-cause mortality data were obtained using record linkage. Survival analyses were performed using Cox proportional hazard models. Among 5000 HCV/HIV co-infected individuals, 1671 (33.4%) had pretreatment anaemia. In a follow-up period of up to 7 years (19,500 person-years), individuals with anaemia had significantly higher mortality rate compared with those without anaemia [144.2 (95% CI: 134.5-154.7) vs 47.5 (44.0-51.2) per 1000 person-years, respectively]. Among individuals with anaemia, HCV treatment was associated with significantly lower mortality rate [66.6 (44.3-100.2) vs 149.6 (139.2-160.5) per 1000 person-years, for treated vs untreated, respectively]. Treatment remained associated with substantial survival benefit after taking into account the effect of multiple comorbidities (hazards ratio: 0.34, 95% CI: 0.21-0.62). These data suggest that HCV/HIV co-infected individuals with pretreatment anaemia have significantly higher mortality compared with those without anaemia. HCV treatment is associated with substantial survival benefit in this group. Additional studies are needed to determine strategies to improve HCV treatment rates among this group.

Association between glycated haemoglobin and the risk of lower extremity amputation in patients with diabetes mellitus-review and meta-analysis.

AIMS/HYPOTHESIS: Diabetes increases the risk of lower extremity amputation (LEA). Although epidemiological studies report positive associations between glycaemia and LEA, the magnitude of the risk is not adequately quantified and clinical trials to date have not provided conclusive evidence about glucose lowering and LEA risk. We synthesised the available prospective epidemiological data on the association between glycaemia measured by HbA(1c) and the risk of LEA in individuals with diabetes. METHODS: We searched electronic databases and reference lists of relevant articles. We considered prospective epidemiological studies that had measured HbA(1c) level and assessed LEA as an outcome among diabetic individuals without acute foot ulcerations or previous history of amputation. Of 2,548 citations identified, we included 14 studies comprising 94,640 participants and 1,227 LEA cases. We abstracted data using standardised forms and obtained data from investigators when required. Data included characteristics of study populations, HbA(1c) assay methods, outcome and covariates. Study-specific relative risk estimates were pooled using random-effects model meta-analysis; heterogeneity was explored with meta-regression analyses. RESULTS: The overall RR for LEA was 1.26 (95% CI 1.16-1.36) for each percentage point increase in HbA(1c). There was considerable heterogeneity across studies (I (2) 76%, 67-86%; p < 0.001), which was not accounted for by recorded study characteristics. The estimated RR was 1.44 (95% CI 1.25-1.65) for type 2 diabetes and 1.18 (95% CI 1.02-1.38) for type 1 diabetes; however, the difference was not statistically significant (p = 0.09). We found no strong evidence for publication bias. CONCLUSIONS/INTERPRETATION: There is a substantial increase in risk of LEA associated with glycaemia in individuals with diabetes. In the absence of conclusive evidence from trials, this paper provides further epidemiological support for glucose-lowering as a strategy to reduce amputation in a population without acute foot ulceration or former amputation; it also provides disease modellers with estimates to assess the overall burden of hyperglycaemia.

Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis.

AIMS/HYPOTHESIS: We examined the association between serum C-reactive protein (CRP) and incident diabetes in a prospective study, and added these data to a literature-based meta-analysis to explore potential sources of heterogeneity between studies. METHODS: We analysed a case-control study nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, including 293 incident diabetes cases and 708 controls. We combined 16 published studies on CRP and incident diabetes in a random-effect meta-analysis. RESULTS: In the EPIC-Norfolk cohort, serum CRP was associated with a higher risk of diabetes after adjusting for age, sex, BMI, family history of diabetes, smoking and physical activity (OR 1.49, comparing the extreme thirds of CRP distribution [95% CI 1.03-2.15], p = 0.03). However, the association was completely attenuated after further adjustment for WHR, serum gamma-glutamyltransferase and serum adiponectin (OR 1.00; 95% CI 0.66-1.51, p = 1.0). In a meta-analysis of 16 published studies with 3,920 incident diabetes cases and 24,914 controls, the RR was 1.72 (95% CI 1.54-1.92), comparing the extreme thirds of CRP distribution, with substantial heterogeneity between studies (I (2) = 52.8%, p = 0.007). CONCLUSIONS/INTERPRETATION: Initial evidence of association between CRP and incident diabetes was confounded by central adiposity, markers of liver dysfunction and adiponectin in the primary analysis. Despite an overall positive association in the meta-analysis, considerable heterogeneity existed between studies. The degree of adjustment for central adiposity and baseline glycaemia explained some of this heterogeneity and suggests that CRP may not be an independent risk factor for type 2 diabetes.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.