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Low HDL cholesterol and the risk of diabetic nephropathy and retinopathy: results of the ADVANCE study.

ABSTRACT: Although low HDL cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and the risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a cohort of patients with type 2 diabetes.A total of 11,140 patients with type 2 diabetes and at least one additional vascular risk factor were followed a median of 5 years. Cox proportional hazards models were used to assess the association between baseline HDL-C and the development of new or worsening microvascular disease, defined prospectively as a composite of renal and retinal events.The mean baseline HDL-C level was 1.3 mmol/L (SD 0.45 mmol/L [range 0.1-4.0]). During follow-up, 32% of patients developed new or worsening microvascular disease, with 28% experiencing a renal event and 6% a retinal event. Compared with patients in the highest third, those in the lowest third had a 17% higher risk of microvascular disease (adjusted hazard ratio 1.17 [95% CI 1.06-1.28], P = 0.001) after adjustment for potential confounders and regression dilution. This was driven by a 19% higher risk of renal events (1.19 [1.08-1.32], P = 0.0005). There was no association between thirds of HDL-C and retinal events (1.01 [0.82-1.25], P = 0.9).In patients with type 2 diabetes, HDL-C level is an independent risk factor for the development of microvascular disease affecting the kidney but not the retina.

SUBMITTER: Morton J

PROVIDER: S-EPMC3476889 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Low HDL cholesterol and the risk of diabetic nephropathy and retinopathy: results of the ADVANCE study.

Morton Jamie J Zoungas Sophia S Li Qiang Q Patel Anushka A AA Chalmers John J Woodward Mark M Celermajer David S DS Beulens Joline W J JW Stolk Ronald P RP Glasziou Paul P Ng Martin K C MK

Diabetes care 20120813 11

<h4>Objective</h4>Although low HDL cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and the risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a cohort of patients with type 2 diabetes.<h4>Research design and methods</h4>A total of 11,140 patients with type 2 diabetes and at least one additional vascular risk factor were followed a median of 5 years. Cox proportional hazards models were used to asses ...[more]

PMID: 22891258

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Project description:We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors.Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women >or=735 mg/L; men >or=619 mg/L) or low HDL-C (n = 42; women <or=387 mg/L; men <or=341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (<1600 mg/L) and triglyceride (<1500 mg/L), and none were treated with lipid-lowering medications. Pre-beta(1) HDL and phospholipid transfer protein concentrations were measured by using commercial kits and lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay.Pre-beta(1) HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) micromol x L(-1) x h(-1); P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) micromol x L(-1) . h(-1); P = 0.03] HDL-C groups. ROC curves for pre-beta(1) HDL in the high-HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61-0.81) for predicting IHD, which increased to 0.92 (0.87-0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-beta(1) HDL was observed (r(2) = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r(2) = 0.56; P < 0.0001).IHD was associated with high pre-beta(1) HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-beta(1) HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease.

Project description:IntroductionWhilst the relationship between lipids and cardiovascular mortality has been well studied and appears to be controversial, very little has been explored in the context of rural-to-urban migration in low-resource settings.ObjectiveDetermine the profile and related factors for HDL-c patterns (isolated and non-isolated low HDL-c) in three population-based groups according to their migration status, and determine the effect of HDL-c patterns on the rates of cardiovascular outcomes (i.e. non-fatal stroke and non-fatal myocardial infarction) and mortality.MethodsCross-sectional and 5-year longitudinal data from the PERU MIGRANT study, designed to assess the effect of migration on cardiovascular risk profiles and mortality in Peru. Two different analyses were performed: first, we estimated prevalence and associated factors with isolated and non-isolated low HDL-c at baseline. Second, using longitudinal information, relative risk ratios (RRR) of composite outcomes of mortality, non-fatal stroke and non-fatal myocardial infarction were calculated according to HDL-c levels at baseline.ResultsData from 988 participants, rural (n = 201), rural-to-urban migrants (n = 589), and urban (n = 199) groups, was analysed. Low HDL-c was present in 56.5% (95%CI: 53.4%-59.6%) without differences by study groups. Isolated low HDL-c was found in 36.5% (95%CI: 33.5-39.5%), with differences between study groups. In multivariable analysis, urban group (vs. rural), female gender, overweight and obesity were independently associated with isolated low HDL-c. Only female gender, overweight and obesity were associated with non-isolated low HDL-c. Longitudinal analyses showed that non-isolated low HDL-c increased the risk of negative cardiovascular outcomes (RRR = 3.46; 95%CI: 1.23-9.74).ConclusionsIsolated low HDL-c was the most common dyslipidaemia in the study population and was more frequent in rural subjects. Non-isolated low HDL-c increased three-to fourfold the 5-year risk of cardiovascular outcomes.

Project description:BackgroundThe prevalence, incidence and risk factors and especially the effect of diabetic nephropathy (DN) and diabetic retinopathy on the risk of chronic limb threatening ischemia (CLTI) have been sparsely studied in individuals with type 1 diabetes (T1D).MethodsThe prospective cohort study consisted of 4697 individuals with T1D from the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study. Medical records were thoroughly reviewed in order to ascertain all CLTI events. The key risk factors were DN and severe diabetic retinopathy (SDR).FindingsThere were 319 events of confirmed CLTI, 102 prevalent events at baseline and 217 incident events during the follow-up of 11.9 (IQR 9.3-13.8) years. The 12-year cumulative incidence of CLTI was 4.6% (95% CI 4.0-5.3). Risk factors included presence of DN, SDR, age, duration of diabetes, HbA1c, systolic blood pressure, triglycerides and current smoking. Sub-hazard ratios (SHRs) according to combinations of DN status and presence (+) or absence (-) of SDR were 4.8 (2.0-11.7) for normoalbuminuria/SDR+, 3.2 (1.1-9.4) for microalbuminuria/SDR-, 11.9 (5.4-26.5) for microalbuminuria/SDR+, 8.7 (3.2-23.2) for macroalbuminuria/SDR-, 15.6 (7.4-33.0) for macroalbuminuria/SDR+ and 37.9 (17.2-78.9) for kidney failure compared with individuals with normal albumin excretion rate and without SDR.InterpretationDiabetic nephropathy, especially kidney failure, is associated with high risk of limb threatening ischemia in individuals with T1D. The risk of CLTI increases gradually according to the severity of diabetic nephropathy. Also, diabetic retinopathy is independently and additively associated with high risk of CLTI.FundingThis research was funded by grants from Folkhälsan Research Foundation, Academy of Finland (316664), Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, Novo Nordisk Foundation (NNF OC0013659), Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, Medical Society of Finland, Sigrid Jusélius Foundation and Helsinki University Hospital Research Funds.

Dataset Information

Low HDL cholesterol and the risk of diabetic nephropathy and retinopathy: results of the ADVANCE study.

Publications

Low HDL cholesterol and the risk of diabetic nephropathy and retinopathy: results of the ADVANCE study.

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