Design of the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with type 2 diabetes.

BACKGROUND: There are few data on the role of lipid lowering in the primary prevention of coronary heart disease (CHD) in diabetic patients. This paper describes the design of a collaborative clinical trial between Diabetes UK, the NHS Research and Development Directorate and Pfizer UK, that addresses this question. METHODS: The Collaborative AtoRvastatin Diabetes Study (CARDS) is a multicentre, randomized, placebo-controlled, double-blind clinical trial of primary prevention of cardiovascular disease in patients with Type 2 diabetes. The primary objective is to investigate whether treatment with the hydroxymethylglutaryl coenzyme A reductase inhibitor, atorvastatin, reduces the incidence of major cardiovascular events. At entry patients have at least one other risk factor for CHD in addition to diabetes, namely current smoking, hypertension, retinopathy, or micro- or macroalbuminuria. At randomization patients have been selected for a serum low-density lipoprotein (LDL) cholesterol concentration < or = 4.14 mmol/l (160 mg/dl) and triglycerides < or = 6.78 mmol/l (600 mg/dl). Randomization was completed in June 2001. Patients will be followed until 304 primary endpoints have accrued (expected date early 2005). The trial includes 2838 men and women aged 40-75 years. This report describes the design and administration of the study and reviews the evidence to date of the effectiveness of lipid-lowering therapy in Type 2 diabetes. CONCLUSIONS: The case for lipid-lowering therapy for the primary prevention of CHD in diabetes has not been demonstrated. CARDS will provide essential information on the extent of any benefits and adverse effects of lipid-lowering therapy in diabetic patients without prior CHD.     

Intensive lipid-lowering strategy in patients with diabetes mellitus.

AIMS: To assess the feasibility of an intensive lipid-lowering strategy in diabetic subjects pursuing target plasma lipid levels. METHODS: Patients with diabetes mellitus (DM), Type 1 or 2, with plasma lipid levels exceeding target values (LDL-cholesterol <2.6 mmol/l, triglycerides < 1.7 mmol/l, HDL-cholesterol > 0.9 mmol/l for men and > 1.1 mmol/l for women) were eligible. After 6-12 weeks of diet and glycaemic control, lipid-lowering medication (simvastatin/gemfibrozil/acipimox) was prescribed in steps of incremental dosages and combinations for 30 weeks. RESULTS: Of all eligible clinic patients, 25% initially responded and finally 12% were entered. Thirty-six patients with Type 1 and 59 with Type 2 DM were studied. Mean baseline lipid levels in Type 1 and Type 2 diabetic subjects were: LDL-cholesterol 3.6 and 3.7 mmol/l, triglycerides 1.7 and 2.2 mmol/l, HDL-cholesterol for men 1.1 and 1.0 mmol/l, and for women 1.4 and 1.2 mmol/l, respectively. All three target values were reached in 66% of the patients. LDL-cholesterol was reduced by 1.2 mmol/l in Type 1 and 1.3 mmol/l in Type 2 diabetic patients and triglycerides by 0.7 mmol/l and 1.1 mmol/l, respectively. HDL-cholesterol increased by 0.15 mmol/l and 0.34 mmol/l in men and women with Type 1 diabetes mellitus, respectively. The cholesterol-triglyceride ratio decreased significantly in VLDL in Type 1 diabetes and in IDL in Type 2 diabetes and increased significantly in HDL in Type 2 DM. CONCLUSIONS: A minority of subjects eligible for intensive lipid lowering agreed to participate in a feasibility study, suggesting a potentially large compliance problem for a general lipid-lowering programme in a diabetes clinic. Nevertheless, intensive lipid lowering with drug combinations can attain the recommended target lipid levels in 66% of subjects with diabetes. With this strategy the plasma lipoprotein composition shifts towards a less atherogenic profile. Subjects with diabetes should therefore receive lipid-lowering therapy tailored to reach target levels, rather than standard dosages, in order to reduce atherogenic risk.     

Stroke prediction and stroke prevention with atorvastatin in the Collaborative Atorvastatin Diabetes Study (CARDS).

AIMS: Patients with Type 2 diabetes have an elevated risk of stroke. The role of lipid levels and diabetes-specific factors in risk prediction of stroke is unclear, and estimates of efficacy of lipid-lowering therapy vary between trials. We examined predictors of stroke and the effect of atorvastatin on specific stroke subtypes in Type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS) [a trial of 2838 participants with mean low-density lipoprotein cholesterol < 4.14 mmol/l, no history of macrovascular disease and randomized to atorvastatin 10 mg daily or placebo]. METHODS: Median follow-up was 3.9 years. Cox regression models were used to estimate the effect of atorvastatin on stroke rate and risk of stroke associated with baseline risk factors. Risk factors that predicted stroke in univariate models were examined in a multivariable model. RESULTS: Independent risk factors predicting stroke were age [10-year increments; hazard ratio (HR) 2.3, P < 0.001], microalbuminuria (albumin : creatinine ratio > 2.5 mg/mmol; HR 2.0, P = 0.007) and glycaemic control (HbA(1c) > 10%; HR 2.7, P = 0.007). Women were at lower risk of stroke (HR 0.3, P = 0.004). Lipids did not predict stroke. Of 60 first strokes, 47 were non-haemorrhagic, 13 were indeterminate and none was definitely haemorrhagic. Atorvastatin treatment was associated with 50% reduction in non-haemorrhagic stroke (95% confidence interval 9%-72%P = 0.024), similar to the 48% reduction (11%-69%) for all strokes combined. CONCLUSIONS: Diabetes-specific risk factors are important predictors of stroke in Type 2 diabetes. Despite the lack of association between baseline lipids and first stroke, there was a reduction of 50% of non-haemorrhagic strokes associated with atorvastatin treatment in the CARDS population.     

Cost-effectiveness of primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes: results from the Collaborative Atorvastatin Diabetes Study (CARDS)

Aims/hypothesis We estimated the cost-effectiveness of atorvastatin treatment in the primary prevention of cardiovascular disease in patients with type 2 diabetes using data from the Collaborative Atorvastatin Diabetes Study (CARDS). Subjects and methods A total of 2,838 patients, who were aged 40 to 75 years and had type 2 diabetes without a documented history of cardiovascular disease and without elevated LDL-cholesterol, were recruited from 32 centres in the UK and Ireland and randomly allocated to atorvastatin 10 mg daily (n = 1,428) or placebo (n = 1,410). These subjects were followed-up for a median period of 3.9 years. Direct treatment costs and effectiveness were analysed to provide estimates of cost per endpoint-free year over the trial period for alternative definitions of endpoint, and of cost per life-year gained and cost per quality-adjusted life-year (QALY) gained over a patient’s lifetime. Results Over the trial period, the incremental cost-effectiveness ratio (ICER) was estimated to be ￡7,608 per year free of any CARDS primary endpoint; the ICER was calculated to be ￡4,896 per year free of any cardiovascular endpoint and ￡4,120 per year free of any study endpoint. Over lifetime, the incremental cost per life-year gained was ￡5,107 and the cost per QALY was ￡6,471 (costs and benefits both discounted at 3.5%). Conclusions/interpretation Primary prevention of cardiovascular disease with atorvastatin is a cost-effective intervention in patients with type 2 diabetes, with the ICER for this intervention falling within the current acceptance threshold (￡20,000 per QALY) specified by the National Institute for Health and Clinical Excellence (NICE). Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorised users.     

Peculiarities of lipid disorders in patients with type II diabetes mellitus: in which cases we should administer statins?

Cardiovascular complications are a principal cause of death rate in the patients with type 2 diabetes, that in turn contribute to cardiovascular diseases and complications in adult population. According to UKPDS data high LDL Ch level is strong predictor of CHD development in patients with type 2 diabetes and its 1 mmol/l level increase, due the coronary risk increase on 57%. Patients with type 2 diabetes have the target levels of lipids enough rigid: the total Ch < 4.5 mmol/l, LDL Ch < 2.5 mmol/l, triglycerides < 1.7 mmol/l and HDL Ch > 1 mmol/l. The results of CARDS study have shown, that the treatment of the type 2 diabetes patients with mild hypercholesterolemia without CHD by atorvastatin in a doze of 10 mg during 5 years decreased cardiovascular risk on 37%, an stroke on 48% and the total death rate on 27%. In practice, 89% of the patients with type 2 diabetes comes to light deviations in Ch level. The lipid spectrum assay of should join to the obligatory diagnostic procedures in all type 2 diabetes patients despite of the age and sex. Statin therapy in the diabetes patients is as necessary as the antidiabetic treatment.     

Atorvastatin and the dyslipidemia of early renal failure

Information about lipid abnormalities and the effect of lipid lowering therapy in the early stage of renal disease is limited, while preventive treatment in this stage might be much more beneficial. Lipid profiles and risk factors were assessed in 150 consecutive, non-diabetic patients. Preventive therapy consisted of cholesterol-reduced diet and atorvastatin 10 mg daily. Patients were considered at risk for cardiovascular disease if LDL-cholesterol was >2.6 mmol/l in the case of manifest cardiovascular disease (n=28) or when they had manifest cardiovascular risk factors (n=105) or if LDL was >3.5 mmol/l (n=17). A total of 128 patients (85%) had increased LDL. In men <60 years and women <40 years, total cholesterol was higher than in the general population. Linear regression analysis showed a decreased creatinine clearance to be significantly associated with the lipid profile. For a 10 ml/min decrease of creatinine clearance, a 0.085 increase of the total cholesterol to HDL ratio was observed (P=0.005). In similar analyses, proteinuria was strongly associated with cholesterol and triglycerides. An increase of 0.28 of the total cholesterol/HDL ratio was observed for each gram per 24 h proteinuria (P<0.001). On atorvastatin 10 mg daily, 30 of 60 treated patients had achieved their target LDL value. On average, LDL-cholesterol was reduced by 39% and triglycerides by 18%. No patient had to interrupt their treatment because of adverse side-effects. In conclusion, the majority of patients had an elevated LDL and other lipid abnormalities. Short-term therapy with atorvastatin and a cholesterol lowering diet appears to be safe and effective. It is probably useful to determine the lipid profile in patients with renal failure already in an early phase and to start lipid lowering treatment as soon as abnormalities are found.     

What does the future hold for diabetic dyslipidaemia?

Preliminary evidence from trials with the HMG-CoA reductase inhibitors (statins), simvastatin and pravastatin, suggests that aggressive treatment of diabetic dyslipidaemia will reduce coronary events. Questions regarding the prevention of cardiovascular events in diabetic patients are now being addressed in prospectively designed trials. The first question is, can aggressive treatment of dyslipidaemia lead to primary prevention of cardiovascular events in patients with type 2 diabetes? This is being addressed in the ongoing Atorvastatin Study for the Prevention of coronary heart disease Endpoints in NIDDM (ASPEN) and the Collaborative AtoRvastatin Diabetes Study (CARDS). These trials will randomize over 4000 patients with type 2 diabetes and no previous myocardial infarction to either atorvastatin or placebo for 4 years. The second question is, are there benefits for aggressive lipid lowering to levels below those recommended in current treatment guidelines, i.e. is lower better? Results from the recent Atorvastatin VErsus Revascularization Treatment (AVERT) trial suggest this to be the case. AVERT showed that, in stable coronary heart disease patients who had been referred for revascularization, aggressive lowering of low density lipoprotein (LDL) cholesterol with atorvastatin 80 mg/day (to a mean level of 2.0 mmol/L [77 mg/dL]) reduced the incidence of ischaemic events by 36% compared with angioplasty and usual care (which reduced LDL cholesterol to 3.1 mmol/dL]). The 36% reduction in events with atorvastatin versus angioplasty and usual care trended towards significance (p=0.048). The benefits of aggressive lipid-lowering therapy are also being investigated in the ongoig Treating to New Targets (TNT) and Incremental Decrease in Endpoints through Aggressive Lipid lowering (IDEAL) trials. These studies will more closely examine the benefits of treating diabetic dyslipidaemia, and will determine how aggressively this abnormal lipid profile should be treated.     

Ethnicity and glycaemic control are major determinants of diabetic dyslipidaemia in Malaysia.

AIMS: To define the prevalence of dyslipidaemia in young diabetic patients in Peninsular Malaysia and the contributory factors of dyslipidaemia in these subjects. METHODS: This is a cross-sectional study involving 848 young diabetic patients from seven different centres, with representation from the three main ethnic groups. Clinical history and physical examination was done and blood taken for HbA1c, fasting glucose, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides. RESULTS: The overall lipids were suboptimal, worse in Type 2 diabetes mellitus (DM) patients compared with Type 1 DM patients. Of the Type 2 patients, 73.2% had total cholesterol > 5.20 mmol/l, 90.9% had LDL-cholesterol > 2.60 mmol/l, 52.6% had HDL-cholesterol < 1.15 mmol/l and 27.3% had serum triglycerides > 2.30 mmol/l. There were ethnic differences in the lipid levels with the Malays having the highest total cholesterol (mean 6.19 mmol/l), and the highest LDL-cholesterol (mean 4.16 mmol/l), while the Chinese had the highest HDL-cholesterol (geometric mean 1.24 mmol/l). Ethnicity was an important determinant of total, LDL- and HDL-cholesterol in Type 2 DM, and LDL- and HDL-cholesterol and triglycerides in Type 1 DM. Glycaemic control was an important determinant of total, LDL-cholesterol and triglycerides in both Type 1 and Type 2 DM. Waist-hip ratio (WHR) was an important determinant of HDL-cholesterol and triglycerides in both types of DM. Gender was an important determinant of HDL-cholesterol in Type 2 DM, but not in Type 1 DM. Socioeconomic factors and diabetes care facilities did not have any effect on the dyslipidaemia. CONCLUSIONS: The prevalence of dyslipidaemia was high especially in Type 2 DM patients. Ethnicity, glycaemic control, WHR, and gender were important determinants of dyslipidaemia in young diabetic patients. Diabet. Med. 18, 501-508 (2001)     

Interactive effect of retinopathy and macroalbuminuria on all-cause mortality, cardiovascular and renal end points in Chinese patients with Type 2 diabetes mellitus.

AIMS: To examine the effect of albuminuria and retinopathy on the risk of cardiovascular and renal events, and all-cause mortality in patients with Type 2 diabetes. METHODS: A post-hoc analysis of 4416 Chinese patients without macrovascular complications at baseline (age 57.6 +/- 13.3 years). Glomerular filtration rate (eGFR) was estimated by the abbreviated Modification of Diet in Renal Disease Study Group Formula, further adjusted for Chinese ethnicity. Clinical end points were all-cause mortality, cardiovascular events (heart failure or angina, myocardial infarction, lower limb amputation, re-vascularization procedures and stroke) and renal end points (reduction in eGFR by more than 50% or eGFR < 15 ml/min/1.73 m2 or death as a result of renal causes or need for dialysis). RESULTS: Compared with individuals without complications, subjects with retinopathy and macroalbuminuria had higher rates of cardiovascular events (14.1 vs. 2.4%), renal events (40.0 vs. 0.8%) and death (9.3 vs. 1.7%, P < 0.001). For composite event of death, cardiovascular and renal events, the presence of retinopathy, microalbuminuria alone, macroalbuminuria alone, retinopathy with microalbuminuria or retinopathy with macroalbuminuria increased the risk [hazard ratio (95% CI)] by 1.61 (1.05 to 2.47; P = 0.04), 1.93 (1.38 to 2.69; P < 0.001), 4.34 (3.02 to 6.22; P < 0.001), 2.59 [1.76 to 3.81; P < 0.001) and 6.83 (4.89 to 9.55; P < 0.001) fold, respectively. The relative excess risk as a result of interaction between retinopathy and macroalbuminuria was 15.31, implying biological interaction in the development of renal events. CONCLUSIONS: In Chinese patients with Type 2 diabetes, retinopathy interacts with macroalbuminuria to increase the risk of composite cardio-renal events.     

Soluble vascular cell adhesion molecule-1 and soluble E-selectin are associated with micro- and macrovascular complications in Type 1 diabetic patients

OBJECTIVE: There are no large studies in Type 1 diabetic patients that have examined the relation between soluble adhesion molecules and micro- and macrovascular outcomes, although the risks of such complications are high. Therefore, the main objective is to examine the relationship between soluble (s) vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin and retinopathy, albuminuria, and cardiovascular disease (CVD) in Type 1 diabetic patients. METHODS: Cross-sectional data on 540 Type 1 diabetic patients, with a mean age of 40 years and diabetes duration of 22 years, from the EURODIAB Prospective Complications Study (PCS) were analysed. Retinopathy was assessed by centrally graded retinal photographs. Albumin excretion rate (AER) was used to define micro- and macroalbuminuria. CVD was defined as having physician diagnosed myocardial infarction (MI), stroke, coronary artery bypass graft (CABG) or angina, or Minnesota coded ischaemic electrocardiograms (ECGs). RESULTS: Unadjusted, there was a positive relationship between sVCAM-1 and sE-selectin with nonproliferative and proliferative retinopathy, micro- and macroalbuminuria, and CVD. After adjustment for age, sex, duration of diabetes, systolic blood pressure (BP), LDL-cholesterol, fasting triglycerides (TGs), smoking, body mass index (BMI), and glycated haemoglobin, as well as other complications, the strongest significant associations were shown between sVCAM-1 and macroalbuminuria, with an odds ratio of 1.83 (1.33-2.53) for every 100 ng/ml increase in sVCAM-1. CONCLUSIONS: In this large sample of Type 1 diabetic patients, it was shown that sVCAM-1 and sE-selectin have positive associations with retinopathy, albuminuria, and CVD. This suggests that adhesion molecules are important in the pathogenesis of vascular complications in Type 1 diabetes.     

Effects of rosuvastatin on lipids, lipoproteins and apolipoproteins in the dyslipidaemia of diabetes.

AIMS: To compare the effects of rosuvastatin and atorvastatin 10 and 20 mg on plasma lipid and lipoprotein profiles in patients with Type 2 diabetes mellitus and triglycerides < or = 6.0 mmol/l. METHODS: A double-blind, randomized, multicentre study to assess the effect of rosuvastatin and atorvastatin, at 10 mg/day for 8 weeks followed by 20 mg/day for a further 8 weeks, on low-density lipoprotein cholesterol (LDL-C), together with a range of secondary lipid and lipoprotein end points. RESULTS: Rosuvastatin reduced mean LDL-C levels from baseline over 16 weeks by 57.4%, while atorvastatin reduced mean LDL-C levels by 46.0% over the same period. The difference in LDL-C reduction between treatments was statistically significant (P < 0.001). Rosuvastatin also produced statistically significantly greater mean reductions from baseline in levels of total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and lipid ratios. More patients achieved European LDL-C (< 2.5 mmol/l) and total cholesterol (< 4.5 mmol/l) goals with rosuvastatin than with atorvastatin. Rosuvastatin was associated with a significantly (P < 0.049) greater mean percentage increase in glycated haemoglobin (HbA(1c)) from baseline compared with atorvastatin; however, patients in both treatment groups maintained good glycaemic control. Both rosuvastatin and atorvastatin were well tolerated. CONCLUSIONS: Greater reductions in LDL-C were achieved with rosuvastatin compared with equal doses of atorvastatin, enabling more patients with Type 2 diabetes to achieve European LDL-C goals.     

Diabetes care and complications in a remote primary health care setting

Prevalence of complications of type 2 diabetes in a remote Australian Indigenous community was measured as part of a population survey of risk factors for diabetes and cardiovascular disease. Information was obtained from history, clinical examination, blood sample and medical records. Forty-three diabetic participants (six newly diagnosed) were assessed from a sample of 339 (12% diabetes prevalence); mean age 50 (range 31-67), duration of diabetes 5.6 (0-15) years, 40% male. Risk factors/complications: 70% with >/= 25, 50% cigarette smokers, HbA1c 8.5 (S.D. 2.9)%, cholesterol 4.8 (0.8)mmol/l, triglycerides 2.7 (1.6)mmol/l, HDL 0.83 (0.2)mmol/l; 60% had albuminuria (micro 38%, macro 22%), 47% were hypertensive, 7% (n = 2) had retinopathy, 24% had peripheral neuropathy, none had peripheral vascular disease, 14% had documented coronary vascular and one participant cerebrovascular disease. Of 37 with previously diagnosed diabetes: 43% were on aspirin, 65% on metformin, 80% with albuminuria on ACE inhibitors. Four additional diabetic participants (not studied) were receiving renal dialysis elsewhere. The results demonstrate on the one hand, very high indices of cardiovascular risk (smoking, hypertension, dyslipidaemia and albuminuria) and on the other, good quality primary health care providing good detection and follow up management of type 2 diabetic patients.     

Coronary heart disease in the statin and aspirin era: are results of clinical trials being put into practice?

Background: We studied the impact of recent advances in coronary prevention by assessing cardiovascular risk factors and their management in 98% of patients admitted to a coronary care unit with acute myocardial infarction (AMI) between January and December 1998 [177 patients, mean age 66±1 (S.E.M.) years, 114 males]. Methods and results: Sixty-two patients had a history of coronary heart disease (CHD). One in four of them was still smoking and 27% had a recorded history of hyperlipidaemia. Only 12 patients with known CHD (19%) were on lipid-lowering treatment. Total cholesterol was above 5 mmol/l in 98/168 (58%) of the patients and LDL-cholesterol was above 3 mmol/l in 91/148 (62%) of the patients. Twenty-eight patients (16%) died during the hospital stay (age 74±2 years). Of 149 patients discharged from hospital, 101 (68%) were treated with a statin, including 85% of the patients with a total fasting cholesterol on admission above 5 mmol/l and 91% with LDL-cholesterol on admission above 3 mmol/l. Sixty-three percent of the patients on a statin were on a dose below that shown in clinical trials to reduce cardiovascular events. Conclusions: Unrecognised and ineffectively treated cardiovascular risk factors were common among patients with documented CHD who were admitted with AMI. Our study provides important background for the implementation of guidelines for the prevention of CHD.     

Statin therapy improves brachial artery vasodilator function in patients with Type 1 diabetes and microalbuminuria.

AIMS: Type 1 diabetes mellitus patients with microalbuminuria have endothelial dysfunction associated with the degree of albuminuria but not with LDL-cholesterol levels. Lipid-lowering agents such as statins may still be of benefit as they can correct endothelial dysfunction by both lipid and non-lipid mechanisms. We therefore examined the effects of atorvastatin on brachial artery endothelial dysfunction in these patients. METHODS: In a double-blind, randomized crossover study, 16 Type 1 diabetes mellitus patients with microalbuminuria received 6 weeks of atorvastatin 40 mg/day or placebo, separated by a 4-week washout. Brachial artery, endothelium-dependent, flow-mediated dilatation (FMD) and endothelium-independent, glyceryl trinitrate-mediated dilatation (GTNMD) were measured. RESULTS: Compared with placebo, atorvastatin produced a significant decrease in apolipoprotein B (34.2%), LDL-cholesterol (44.1%) (all P < 0.001), and oxidized-LDL (35.7%, P = 0.03). There was a non-significant increase in plasma cGMP (P = 0.13) on atorvastatin. FMD and GTNMD increased significantly on atorvastatin (FMD: atorvastatin +1.8 +/- 0.4%; placebo +0.2 +/- 0.4%, P = 0.007); (GTNMD: atorvastatin +1.3 +/- 0.9%; placebo -1.2 +/- 0.6%, P = 0.04). An increase in cGMP was independently correlated with an increase in FMD on atorvastatin (adjusted (R2) 0.41, P = 0.02). CONCLUSION: Atorvastatin improves endothelium-dependent and independent vasodilator function of the brachial artery in Type 1 diabetes mellitus patients with microalbuminuria. This may relate to pleiotropic effects of statins, in particular reduced oxidative stress and increased availability of nitric oxide.     

Renal and retinal microangiopathy after 15 years of follow-up study in a sample of Type 1 diabetes mellitus patients

PURPOSE: In the present study, the objective is to determine the epidemiological risk factors in the appearance of diabetic retinopathy and nephropathy in 112 Type 1 diabetic patients after 15 years. METHODS: A 15-year follow-up study was done in a cohort of 112 consecutive Type 1 (IDDM) diabetes mellitus patients without diabetic retinopathy or nephropathy at enrolment in 1990. We studied the incidence of diabetic retinopathy and/or microalbuminuria. The epidemiological risk factors included in the study were gender, diabetes duration, HbA(1c) levels, arterial hypertension, levels of triglycerides and fractions of cholesterol (HDL-cholesterol and LDL-cholesterol). RESULTS: The incidence of diabetic retinopathy was 55.40% at the end of study; the risk factors associated were duration of diabetes mellitus (P<.001), high levels of HbA(1c) (P=.009), presence of arterial hypertension (P=.007) and high levels of LDL-cholesterol (P=.002). The incidence of microalbuminuria was 41.07% and that of overt nephropathy, 19.60%; the risk factors associated were high levels of HbA(1c) (P<.001) and presence of arterial hypertension (P=.023). At the end of study, four groups of patients were formed: patients without microalbuminuria or retinopathy, patients with microalbuminuria only, patients with retinopathy only and patients with retinopathy and microalbuminuria. From the results of the discriminate analysis, we may assume that for the development of retinal lesions only, in the diabetes mellitus, the duration of the disease, the high levels of HbA(1c) and the arterial hypertension are most important, and for the development of renal and retinal lesion simultaneously, the important factor is poor control of glycemia measured by levels of HbA(1c) and arterial hypertension. CONCLUSIONS: In conclusion, microalbuminuria correlated well with severe forms of diabetic retinopathy, and at the end of the study, two groups of patients had been configured: the first group had developed only diabetic retinopathy, and the second, their patients with diabetic retinopathy together with renal lesion (microalbuminuria). For the first group, the duration of diabetes mellitus was the most important risk factor, and for the second group, the levels of HbA(1c) and blood pressure were the most important.     

Nephropathy, but not retinopathy, is associated with the development of heart disease in Type 1 diabetes: a 12-year observation study of 462 patients.

AIMS: To study the occurrence of heart disease and death in Type 1 diabetic patients and evaluate whether presence of microangiopathy, i.e. nephropathy and retinopathy, was associated with the outcome. METHODS: A 12-year observation study of 462 Type 1 diabetic patients without a previous history of heart disease at baseline who were treated under routine care in a hospital out-patient clinic. RESULTS: A total of 85 patients developed signs of heart disease, i.e. myocardial infarction (n = 41), angina (n = 23), and heart failure (n = 17) and 56 patients died. The mortality for patients without signs of heart disease during the observation period was 7.6% compared with 51% in patients with myocardial infarction (P < 0.001), 26% in patients with angina (P < 0.01) and 65% in patients with heart failure (P < 0.001). The relative risk for death was 9.0 (P < 0.001) and 2.5 (P < 0.05) times higher in patients with macroalbuminuria and microalbuminuria, respectively. The risk for cardiovascular death was 18.3 times (P < 0.001) higher in patients with macroalbuminuria compared with patients with normoalbuminuria. In patients with sight-threatening retinopathy, the relative risk for death was 7.0 times higher (P < 0.01) and the risk for coronary heart disease events 4.4 times higher (P < 0.05) compared with patients with no retinopathy. However, when retinopathy was adjusted for presence of macroalbuminuria, this association disappeared. CONCLUSION: This study shows a high incidence of heart disease in patients with Type 1 diabetes. The worse prognosis was seen in patients with sight-threatening retinopathy and macroalbuminuria and microalbuminuria at baseline. Macroalbuminuria and microalbuminuria were independently associated with a high risk for heart disease and death while the association with sight-threatening retinopathy only occurred in the presence of nephropathy.     

The FIELD study presented and published. Unconvincing results of fenofibrates in diabetic patients

The prognosis of the patients with the Type II diabetes mellitus without myocardial infarction is as serious as the prognosis of the patients who had experienced myocardial infarction without diabetes mellitus. Consequently there is a big interest of IHD prevention options in diabetic patients, not only by hypertension therapy, but also by hypolipidemic treatment. That is why the results of FIELD study were expected with a great interest. FIELD study randomized 9 795 patients with the Type II diabetes mellitus and initial values of total cholesterol 3.0 to 6.5 mmol/l and in addition with total cholesterol/HDL-cholesterol rate > or = 4.0 or with the values of plasmatic triglycerides between 1.0 and 5.0 mmol/l for treatment with 200 mg of micronized phenophibrate or placebo. As phenophibrate positively influences the typical lipid disorder at diabetic patients, the throughout positive results of phenophibrate had been expected. Study did not fulfil the primary objective of the study of coronary deaths/ non fatal myocardial infarctions (insignificant decrease by 11%). Although phenophibrate significantly decreased non fatal myocardial infarctions and myocardial revascularizations, total mortality and cardiovascular mortality were not positively influenced and they even show non significant aggravating trend. Moreover, the positive effect of phenophibrate on non fatal myocardial infarctions and revascularizations was present only at the persons who had not experienced a cardiovascular disease and only at the persons under 65 years. Phenophibrate positively influenced some diabetic micro vascular complications (nephropathy and retinopathy). Thus, the results of FIELD study present a disappointment and that is why the recommendations of the statin therapy as a priority therapy of dislipidemia stay unchanged also for the patients with Type II diabetes mellitus.     

The UKPDS: implications for the dyslipidaemic patient

The UK Prospective Diabetes Study (UKPDS) is the largest intervention trial to date of patients with type 2 diabetes, involving 5102 newly diagnosed diabetic patients. Results showed that 59% of patient deaths were from cardiovascular disease. While intensive treatment of glucose produced a significant 25% reduction in microvascular endpoints compared with diet only (p=0.0099), patients with type 2 diabetes usually have a lipid profile that is highly atherogenic. In the UKPDS, intensive treatment of hyperglycaemia and hypertension did not improve lipid levels. In patients without diabetes, lipid-lowering therapy has been shown to reduce the risk of cardiovascular events in both primary and secondary prevention trials. Currently, a number of large-scale trials of lipid-lowering therapy in patients with diabetes are ongoing. For example, the Lipids in Diabetes Study will determine whether lipid lowering with a statin or fibrate can substantially reduce cardiovascular morbidity and mortality in 5000 patients with type 2 diabetes. The Atorvastatin Study for the Prevention of coronary heart disease ENdpoints (ASPEN) is comparing double-blind treatment with atorvastatin and placebo in 2250 US diabetic patients without coronary heart disease, while a sister trial in the UK, the Collaborative AtoRvastatin Diabetes Study (CARDS), is enrolling 1820 diabetic patients. The results from these trials may provide information that which will help determine the future management of diabetic dyslipidaemia.     

Lipid levels and the use of lipid-lowering agents in England and Scotland.

OBJECTIVE: Preventing cardiovascular events with lipid-lowering drugs has been established in several trials reported since 1994. Consequently national guidelines recommend statins for those with established cardiovascular disease (CVD) and those at high risk of developing CVD. We evaluated blood lipid levels, and compare treatment and control of dyslipidaemia in English and Scottish adults with national recommendations for lipid lowering. DESIGN AND METHODS: In 1998 the nationally-representative Health Survey for England and the Scottish Health Survey included valid cholesterol results for 9631 (England) and 6065 (Scotland) adults aged 16-74. Mean blood levels of total, high-density lipoproteins (HDL-), and total:HDL-cholesterol ratio; prevalence of elevated total cholesterol levels, and total:HDL-cholesterol ratios; prevalence of use of lipid-lowering agents in high risk subgroups; and lipid levels of those on treatment were calculated. RESULTS: Levels of dyslipidaemia, treatment and control were not significantly different between Scotland and England. Combining these data, mean total cholesterol levels were 5.43 and 5.48 mmol/l in men and women respectively; and mean HDL-cholesterol levels were 1.29 and 1.56 mmol/l. Overall 64.6% of adults had a total cholesterol > or =5 mmol/l, 24.6% had a total:HDL ratio > or =5 and 2.3% reported taking lipid-lowering drugs. Treatment rates among those with a total cholesterol >5 mmol/l and a history of coronary heart disease or stroke, hypertension, or diabetes, were 27.3%, 15.4% and 17.8% respectively, and control rates (total cholesterol <5 mmol/l) among those treated were 45.3%, 38.5% and 32.7%. CONCLUSIONS: Low treatment rates with lipid-lowering drugs existed overall, among high-risk patients suitable for primary prevention, and among those with established cardiovascular disease.