MICROALB study: screening for microalbuminuria in type 2 diabetic hypertensive patients by general practitioners in France

OBJECTIVE: To determine the prevalence of microalbuminuria (MAU) detected by a specific urinary strip in type 2 diabetic hypertensive patients in metropolitan France. METHOD: Screening for MAU with a semi-quantitative strip measuring the albumin/creatinine ratio was performed by general practitioners (GPs) in 6 type 2 diabetic hypertensive patients. This screening method was considered reliable if a preliminary search for proteinuria was performed with a usual strip and the quality of the MAU reading was good. RESULTS: 3347 GPs screened 19,714 patients (60% M, average age 64 +/- 10 years): 43.3% had MAU. MAU screening was considered reliable for 6679 patients (61.8% M, average age 65 +/- 10 years): 48.5% had MAU (alb/creat ratio between 30 and 300 mg/g), and 10.7% had manifest MAU (alb/creat ratio >300 mg/g). In all cases, the prevalence of MAU increased with the severity of hypertension. In the population with a reliable MAU screen, the analysis of risk factors according to the level of MAU yielded the following results: [table: see text]. In the MAU+ group, the need for multiple antidiabetic (including insulin) and antihypertensive drugs was more frequent. In contrast to current guidelines, only a minority of patients received an antiplatelet agent (approximately 33%). CONCLUSION: Despite recommendations, screening for proteinuria in type 2 diabetic hypertensive patients is seldom performed. However, the prevalence of MAU was high in this patient population. The prevalence of comorbidities and risk factors was significantly higher in the MAU+ group, with less frequent BP control despite a more aggressive antihypertensive treatment.     

Hypertension and microalbuminuria: the new detrimental duo

Excretion of albumin with urine (UAE) in small amounts, i.e. microalbuminuria (MAU), also referred to as “incipient nephropathy”, has long been considered a marker of early nephropathy and increased cardiovascular risk in the specific setting of diabetes mellitus. However, numerous clinical studies found an association between MAU and other cardiovascular risk factors, target organ damage and risk of cardiovascular disease in clinical contexts different from diabetes and including arterial hypertension. The present article reviews the available evidence on the clinical value of MAU in subjects with primary hypertension. In these subjects, prevalence of MAU varied from about 4% to 46% across different studies and these differences may be explained by the huge intra-individual variability in UAE, discrepancies in the technique of measurement and different definitions of MAU. A direct and continuous association between UAE and blood pressure (BP) has been found in many studies. A continuous association between UAE and left ventricular mass has also been found in most studies. In contrast, it is not yet clear whether the association between UAE and other factors including age, gender, smoking, ethnicity, insulin resistance, lipids and obesity is independent or mediated by confounders, particularly BP. From a prognostic standpoint, several longitudinal studies showed an association between MAU and the risk of future cardiovascular disease. Of particular note, in some of these studies the incidence of major cardiovascular events progressively increased with UAE starting below the conventional MAU thresholds. Thus, besides being a direct risk factor for progressive renal damage, MAU can be considered a marker, which integrates and reflects the long-term level of activity of several other detrimental factors on cardiovascular system. Antihypertensive treatment reduces UAE and such effect may be detected after just a few days of treatment. Among available antihypertensive drugs, angiotensin-converting enzyme (ACE) inhibitors and the angiotensin II receptor antagonists seem to be superior to other antihypertensive drugs in reducing UAE. The dual blockade of the renin-angiotensin system with an ACE inhibitor and an angiotensin II receptor antagonist is a new and promising approach to control UAE in hypertensive patients. Determination of MAU is recommended in the initial work-up of subjects with primary hypertension.     

Are β-blockers efficacious as first-line therapy for hypertension in the elderly?

The aim of this paper is to assess antihypertensive efficacy of β-blockers and their effects on cardiovascular morbidity and mortality and all-cause mortality in elderly patients with hypertension. Randomized placebo-controlled trials, trials with untreated controls, and trials comparing antihypertensive drugs were selected from the literature. The relative risk reduction of primary endpoints and 95% confidence intervals were calculated. There were six trials in which elderly patients were treated with β-blockers for hypertension (three trials were placebo-controlled, one trial had untreated controls, and two trials compared antihypertensive drugs). There was no study with monotherapy of β-blockers. In combination with diuretics, β-blockers were superior to placebo and untreated controls in preventing cardiovascular events, especially strokes, but there was no superiority of β-blockers to angiotensin-converting enzyme inhibitors and calcium antagonists in preventing cardiovascular morbidity and mortality and total mortality in elderly patients with hypertension. β -Blockers are only efficacious in combination with diuretics in preventing cardiovascular morbidity and mortality in elderly patients with hypertension.     

Levels of cardiovascular risk factors in type 2 diabetes mellitus are dependent on the stage of proteinuria.

Levels of cardiovascular risk factors were determined in 75 patients with Type 2 diabetes mellitus. The patients were divided into three groups according to their urinary protein excretion (UPE): (a) normal proteinuria (less than or equal to 70 mg d-1); (b) microproteinuria (70-500 mg d-1); and (c) macroproteinuria (greater than 500 mg d-1). A significant stepwise increase in mean systolic blood pressure, LDL-cholesterol and fibrinogen levels was observed from the first to the third investigated group of patients. Mean apoprotein B levels were significantly increased in the group with macroproteinuria compared to the other two groups. Significant linear correlations were found between UPE and LDL-cholesterol, total cholesterol, apoprotein B, creatinine, systolic blood pressure and diabetes duration. In summary, it is concluded that the levels of some cardiovascular risk factors increase with the stage of proteinuria in Type 2 diabetes mellitus.     

Losartan and end-organ protection--lessons from the RENAAL study

BACKGROUND: The Reduction in ENdpoints with the Angiotensin Antagonist Losartan (RENAAL) study reported that losartan delayed the progression of renal disease in patients with type 2 diabetes and nephropathy. Diabetic or renally impaired patients are at high cardiovascular risk, a risk potentially increased in patients with both conditions. HYPOTHESIS: This post hoc analysis examined whether baseline proteinuria was predictive of cardiovascular outcomes, and whether losartan modifies the risk of cardiovascular outcomes in these patients given its renal-protective effects. METHODS: The RENAAL study compared losartan with placebo (in addition to conventional antihypertensive medications) in type 2 diabetic patients with proteinuria. Morbidity and mortality due to cardiovascular causes were ascertained, and the relationship between baseline proteinuria and cardiovascular outcome was determined. The effect of treatment with losartan was examined using three time-to-event analyses of composite cardiorenal outcomes as described below. RESULTS: Increasing baseline proteinuria was associated with significantly increased risk of myocardial infarction (MI) and all-cause or cardiovascular death, but not stroke. Losartan significantly reduced the risk for the combined endpoint of end-stage renal disease (ESRD), MI, stroke, or death by 21% (p < or = 0.005), irrespective of whether all-cause or cardiovascular death was included in the analysis. In addition, losartan reduced the risk for the composite of ESRD or cardiovascular death by 19.2% (p < 0.05). CONCLUSION: In patients with type 2 diabetes and nephropathy, there is an increased risk of MI and cardiovascular or all-cause mortality. Treatment with losartan is associated with a reduction in proteinuria, a delay in the onset of ESRD, and no increased risk of cardiovascular events in this pre-ESRD population.     

Mortality and Morbidity in Treated Hypertensive Type 2 Diabetic Patients with Micro- or Macroproteinuria

In order to describe the natural history of high risk diabetic patients treated for hypertension we have followed a sequential sample of 100 hypertensive Type 2 diabetic patients with elevated urinary protein excretion (≥60 mg 24 h⁻¹) for a period of 1–7 years. Antihypertensive treatment was instituted in all patients and, in addition, the patients were offered the possibility of participation in an intensified antihypertensive therapy programme. After a mean follow-up of 4 years overall mortality was 13 %. Nineteen percent of all patients experienced a cardiovascular event and 7 % a cerebrovascular event. In conclusion, in this study the overall mortality was lower that previously reported in proteinuric Type 2 diabetic patients. Antihypertensive treatment may account for this outcome.     

高血压患者微量白蛋白尿与动态动脉硬化指数的相关性

背景目前国内外研究发现微量白蛋白尿(MAU)与动态动脉硬化指数(AASI)在一定程度上可预测心血管事件及死亡,但MAU与AASI的相关性尚不明确。目的探讨MAU与血压昼夜节律、AASI等动态血压指标之间的关系。方法筛选无糖尿病和其他致MAU阳性因素的高血压患者400例,其中MAU阳性患者(MAU组)98例,随机抽取302例MAU阴性患者中30例为对照组(NMAU组),分别测定其体质量指数(BMI)、空腹血糖、血脂、肾功能,并行24 h动态血压监测(ABPM)及MAU测定,计算AASI和昼夜节律,进一步在MAU组间进行相关性分析。结果MAU阳性率为24.5%(98/400)。MAU组患者高血压病程、总肌酐、夜间脉压、AASI水平显著高于NMAU组(P<0.05)。MAU组中77例患者的动态血压昼夜节律呈非杓型改变,占78.6%,明显高于NMAU组的60.0%(P<0.05)。多元线性逐步回归结果显示MAU与AASI具有明显的相关性(β=0.75,P<0.01)。结论高血压患者MAU阳性与动态血压脉压增加、昼夜节律改变、AASI值增大相关联。     

Prognostic value of plasma soluble P-selectin and von Willebrand factor as indices of platelet activation and endothelial damage/dysfunction in high-risk patients with hypertension: a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial

BACKGROUND: Abnormal levels of prothrombotic markers have been described in hypertension, but no such marker has yet been shown to reliably predict cardiovascular outcomes in hypertension. We hypothesized that raised circulating levels of soluble P-selectin (sP-sel, an index of platelet activation) and/or von Willebrand factor (vWF, an index of endothelial damage/dysfunction) would predict vascular events in patients treated for cardiovascular risk. METHODS: We measured vWF and sP-sel levels by an ELISA in 234 hypertensive participants with no prior cardiovascular events who were participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Plasma vWF and sP-sel levels were related to the subsequent cardiovascular events over a mean (SD) follow-up period of 59.6 (19) months. RESULTS: Plasma sP-sel was a significant predictor of myocardial infarction (P = 0.03), with the greatest risk amongst those with the highest sP-sel levels. sP-sel did not predict cerebrovascular events (P = 0.53) or composite cardiovascular events (P = 0.06). No significant relationships were found between vWF levels and outcomes. There was no relationship to the presence or absence of diabetes mellitus (DM) at baseline or subsequent development of DM during the follow-up period. CONCLUSIONS: Among 'high-risk' patients with hypertension, raised levels of sP-sel (platelet activation) were predictive of myocardial infarction. Levels of vWF (endothelial damage/dysfunction) were not associated with coronary events and neither marker predicted cerebrovascular or composite cardiovascular endpoints. Platelets (or P-selectin) might represent a target for novel therapies or an adjunctive aid to risk stratification in the setting of hypertension.     

Effect of antihypertensive treatment on the long-term outcome of patients discharged after acute ischemic stroke

We aimed to evaluate the effects of the five main classes of antihypertensive agents on the long-term outcome of 313 consecutive patients discharged after acute ischemic stroke (36.4% males, age 78.5 ± 6.3 years). One year after discharge, the functional status [evaluated with the modified Rankin scale (mRS)], the occurrence of cardiovascular events, and vital status were recorded. Patients prescribed angiotensin receptor blockers (ARBs) had lower mRS than patients not prescribed ARBs (1.7 ± 2.0 vs. 2.9 ± 2.5, respectively; p = 0.006). The rates of adverse outcome (mRS 2-6) and cardiovascular events did not differ between patients prescribed each one of the major classes of antihypertensive agents and those not prescribed the respective class. Patients who were prescribed ARBs had lower risk of death during follow-up than patients who did not receive ARBs (9.4 and 26.9%, respectively; p < 0.05). In binary logistic regression analysis, the only independent predictor of all-cause mortality during follow-up was the mRS at discharge (relative risk 1.69, 95% confidence interval 1.25–2.28; p < 0.001). In conclusion, in patients discharged after acute ischemic stroke, administration of ARBs appears to have a more beneficial effect on long-term functional outcome and all-cause mortality than treatment with other classes of antihypertensive agents.     

High blood pressure and diabetes mellitus: are all antihypertensive drugs created equal?

OBJECTIVE: To analyze the available data to assess the benefits of antihypertensive therapy in hypertensive patients with diabetes mellitus. METHODS: A MEDLINE search of English-language articles published until June 1999 was undertaken with the use of the terms diabetes mellitus, hypertension or blood pressure, and therapy. Pertinent articles cited in the identified reports were also reviewed. Included were only prospective randomized studies of more than 12 months' duration that evaluated the effect of drug treatment on morbidity and mortality in diabetic hypertensive patients. We estimated the risk associated with combination of diabetes mellitus and hypertension and the effect of treatment on morbidity and mortality. RESULTS: The coexistence of diabetes mellitus doubled the risk of cardiovascular events, cardiovascular mortality, and total mortality in hypertensive patients (approximate relative risk of 1.73-2.77 for cardiovascular events, 2.25-3.66 for cardiovascular mortality, and 1.73-2.18 for total mortality). Intensive blood pressure control to levels lower than 130/85 mm Hg was beneficial in diabetic hypertensive patients. All 4 drug classes-diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists-were effective in reducing cardiovascular events in diabetic hypertensive patients. In elderly diabetic patients with isolated systolic hypertension, calcium antagonists reduced the rate of cardiac end points by 63%, stroke by 73%, and total mortality by 55%. In more than 60% of diabetic hypertensive patients, combination therapy was required to control blood pressure. CONCLUSIONS: Intensive control of blood pressure reduced cardiovascular morbidity and mortality in diabetic patients regardless of whether low-dose diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, or calcium antagonists were used as a first-line treatment. A combination of more than 1 drug is frequently required to control blood pressure and may be more beneficial than monotherapy.     

Left ventricular concentric geometry during treatment adversely affects cardiovascular prognosis in hypertensive patients

Left ventricular (LV) mass and geometry predict risk for cardiovascular events in hypertension. Regression of LV hypertrophy (LVH) may imply an important prognostic significance. The relation between changes in LV geometry during antihypertensive treatment and subsequent prognosis has not yet been determined. A total of 436 prospectively identified uncomplicated hypertensive subjects with a baseline and follow-up echocardiogram (last examination 72+/-38 months apart) were followed for an additional 42+/-16 months. Their family doctor gave antihypertensive treatment. After the last follow-up echocardiogram, a first cardiovascular event occurred in 71 patients. Persistence of LVH from baseline to follow-up was confirmed as an independent predictor of cardiovascular events. Cardiovascular morbidity and mortality were significantly greater in patients with concentric (relative wall thickness > or =0.44) than in those with eccentric geometry (relative wall thickness <0.44) in patients presenting with LVH (P=0.002) and in those without LVH (P=0.002) at the follow-up echocardiogram. The incidence of cardiovascular events progressively increased from the first to the third tertile of LV mass index at follow-up (partition values 91 and 117 g/m2), but for a similar value of LV mass index it was significantly greater in those with concentric geometry (OR: 4.07; 95% CI: 1.49 to 11.14; P=0.004 in the second tertile; OR: 3.45; 95% CI: 1.62 to 7.32; P=0.001 in the third tertile; P<0.0001 in concentric versus eccentric geometry). Persistence or development of concentric geometry during follow-up may have additional prognostic significance in hypertensive patients with and without LVH.     

Older age should not be a barrier to the treatment of hypertension

Commentaries and debates at national medical meetings have fuelled the controversy about treatment of hypertension in patients aged 80 years and older. A double-blind, randomized, placebo-controlled trial was, therefore, indicated to settle the dispute about whether antihypertensive drug therapy is efficacious or harmful in these patients. Results from HYVET (Hypertension in the Very Elderly Trial) showed that, at 2-year follow-up, antihypertensive drug therapy with indapamide, plus perindopril if needed, reduced fatal or nonfatal stroke by 30%, fatal stroke by 39%, all-cause mortality by 21%, cardiovascular death by 23%, and heart failure by 64%. These results indicate that hypertensive patients aged 80 years and older should be treated with antihypertensive drugs.     

Increased cardiovascular events in hypertensive patients with insulin resistance: a 13-year follow-up

Insulin resistance (IR) is commonly associated with other cardiovascular risk factors and is considered an independent risk factor for cardiovascular disease and events. The hyperinsulinemic euglycemic clamp technique is considered the gold standard for evaluating IR, but this technique is cumbersome and not easily applicable in large studies. Therefore, there are no long-term follow-up published studies on the relationship between IR determined by this technique and cardiovascular outcome. Thirteen years ago we performed a hyperinsulinemic euglycemic clamp in 31 hypertensive patients, 16 of whom manifested IR and 15 had normal insulin sensitivity.Thirteen years later we were able to re-evaluate or obtain medical records for all these patients. Over these years, 11 of the 16 insulin resistant patients developed cardiovascular disease and events, including two cardiovascular deaths, two myocardial infarctions, one angina pectoris, one peripheral vascular disease, and five carotid plaques or stenosis. Moreover, two patients developed new onset diabetes, one proteinuria and two impaired kidney function. Among insulin-sensitive patients, one developed peripheral vascular disease, one new onset diabetes and one proteinuria.In conclusion, this is the first longitudinal study of the relationship between insulin resistance, measured by the hyperinsulinemic euglycemic clamp and cardiovascular disease and events in a small cohort of patients with essential hypertension. The data suggest that hypertensive patients with IR are at greater risk of developing cardiovascular disease and events than hypertensive patients with normal insulin sensitivity.     

无症状性心房颤动患者临床特征和预后分析

目的:本研究旨在分析无症状性心房颤动(房颤)患者的临床特征和预后情况.方法:回顾性分析2015年9月至2019年7月在金塔县人民医院住院期间确诊有心房颤动的患者426例,根据欧洲心律学会(EHRA)房颤症状评分将其分为无症状性房颤组(n=122)和症状性房颤组(n=304).比较两组患者的临床特征,通过多因素Logis...     

Increases in Serum Lipids During Pregnancy in Type 1 Diabetic Women with Nephropathy

During pregnancy women with Type 1 diabetes do not differ from normal women with respect to pregnancy-associated changes in serum lipid levels. However influence of diabetic nephropathy on lipoprotein metabolism in pregnancy has not been described previously. Changes in lipids were compared during and after pregnancy in 10 Type 1 diabetic women without macroproteinuria as well as in 5 diabetic women with macroproteinuria due to diabetic nephropathy. In the pregnant women with macroproteinuria, compared to the diabetic women without macroproteinuria, we observed both significantly higher total and percent increases in serum levels of total cholesterol (97% versus 48%) and of LDL-cholesterol (137% versus 50%), which had risen progressively throughout gestation. The percent increases in serum triglycerides (115% versus 128%) were similar in both patient groups. Metabolic control was improved during pregnancy in both groups of women. Renal function remained normal throughout pregnancy in the diabetic women without nephropathy and worsened during pregnancy in the proteinuric women. The mean protein excretion showed a physiological rise from 0.107 ± 0.040 g 24 h^?1 before pregnancy to 0.336 ± 0.234 g 24 h^?1 in the third trimester in the non-proteinuric women, and an increase from 2.2 ± 1.0 to 7.1 ± 1.7 g 24 h^?1 during the same period in the women with macroproteinuria. Therefore, it is concluded that the greater increase in serum lipid levels during pregnancy in the women with pre-existing diabetic nephropathy can mainly be explained by the concomitant increase in proteinuria associated with development of the nephrotic syndrome in these patients.     

A review of renal, cardiovascular and mortality endpoints in antihypertensive trials in diabetic patients

Renal disease is highly prevalent in people with type 2 diabetes, and co-existence with hypertension increases the risk of cardiac events and mortality. Despite many large randomized trials, controversies remain regarding optimal antihypertensive therapy in diabetic patients, including whether some classes of antihypertensive drugs have specific renal protective properties, and the relationships between renal, cardiovascular and mortality endpoints. In this article, we review landmark antihypertensive drug trials from the last two decades in patient populations composed, or including substantial proportions, of patients with type 2 diabetes. Several points emerge. Firstly, treatment effects can vary widely among different renal, cardiovascular and mortality endpoints. Secondly, combinations of antihypertensive drugs vary in their ability to prevent major renal and cardiovascular events, even if they produce similar reductions in blood pressure. Thirdly, simply adding further antihypertensive drugs may not improve outcomes, even if it produces further reductions in blood pressure. In most trials, a reduction in microalbuminuria was associated with evidence of renal protection, but further evidence is needed relating changes in proteinuria with cardiovascular risk. The study that aligns best with the current reappraisal of ESH guidelines, with regard to blood pressure goals, use of an adequate combination and simultaneously protecting the kidney and the cardiovascular system, is the ADVANCE study.     

Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes

Aims/hypothesis: Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes. Methods: In a cohort study including 430 patients with Type II diabetes, baseline urinary samples were analysed for orosomucoid and albumin. Mean follow-up was 2.4 years. Results: We found that 188 (44 %) patients had normal and 242 (56 %) patients had increased urinary orosomucoid excretion rates. During the study period 41 patients died; out of these 23 patients died of cardiovascular diseases. Odds ratio for all-cause mortality was 2.50 (95 % CI 1.00–6.22) and odds ratio for cardiovascular mortality was 9.81 (1.31–73.6) having increased urinary orosomucoid excretion rate at baseline (odds ratios adjusted for age, sex, duration of diabetes, cardiovascular diseases, weight, medication, HbA_{1 c}, plasma creatinine and urinary albumin excretion rate). Urinary albumin excretion rate was an independent predictor of all-cause mortality when urinary orosomucoid excretion rate was not included in the analysis. Subgroup analysis revealed that 39 % of the patients with normal urinary albumin excretion rate (n = 251) had increased urinary orosomucoid excretion rates and that these patients had a higher cardiovascular mortality (p = 0.007) than patients with normal urinary albumin excretion rate and normal urinary orosomucoid excretion rates. Conclusion/interpretation: We found that urinary orosomucoid excretion rate predicted all-cause and cardiovascular mortality in patients with Type II diabetes independently from other risk factors. [Diabetologia (2002) 45: 115–120] Received: 24 July 2001 and in revised form: 17 September 2001     

Regression of Small Resistance Artery Structural Alterations in Hypertension by Appropriate Antihypertensive Treatment

Regardless of the mechanisms that initiate the rise of blood pressure, the development of structural changes in the systemic vasculature is the end result of established hypertension. Indices of small resistance artery structure, such as the ratio of tunica media to internal lumen, may have a strong prognostic significance in hypertensive patients, over and above all other known cardiovascular risk factors. Hence, the regression of vascular alterations seems to be an appealing goal for antihypertensive treatment. Different antihypertensive drugs may have different effects on vascular structure. Complete normalization of small resistance artery structure was demonstrated in hypertensive patients after long-term and effective antihypertensive therapy with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium antagonists. Little or no improvement was observed with β-blockers or diuretics. Evidence from several studies suggests that some antihypertensive drugs are more effective than others in reversing microvascular structural alterations in hypertension.     

Niere und Hypertonie

In patients with chronic kidney disease elevated blood pressure is a common finding, but primary hypertension can also damage healthy kidneys. Renal outcome is strictly dependent on blood pressure, no matter whether the kidneys are cause or consequence of hypertension. Furthermore, hypertension and kidney disease are strong cardiovascular risk factors. In every patient diagnosed with hypertension glomerular filtration rate has to be checked. Proteinuria and structural abnormalities of the kidneys should be ruled out. Patients with a decreased glomerular filtration rate, proteinuria or pathologic ultrasound should be seen by a nephrologist. A strict antihypertensive therapy (blood pressure <130/80 mmHg) can substantially improve the prognosis of hypertensive renal patients. In patients with kidney damage, inhibitors of the renin-angiotensin-system are preferred. To avoid adverse events a close monitoring of antihypertensive therapy is warranted.     

Cardiovascular Risk Factors in Type I (Insulin-dependent) Diabetic Patients with and without Proteinuria

ABSTRACT. In diabetes mellitus cardiovascular mortality among patients with increased urinary albumin excretion seems to be higher than in patients with normal urinary albumin excretion. Therefore we investigated blood pressure, total cholesterol, fibrinogen and in vivo platelet adhesion in 61 patients with type I (insulin-dependent) diabetes, 39 without complications, such as retinopathy or proteinuria and 22 with proteinuria and slightly elevated serum creatinine. The two groups had similar age, sex, diabetes duration and glucose control. Blood pressure, total cholesterol, fibrinogen and in vivo platelet adhesion were all significantly elevated in patients with proteinuria (p<0.01), whereas these parameters were normal in the uncomplicated diabetic patients, independent of diabetes duration. The mortality of cardiovascular disease during 20 years' follow-up was significantly higher among patients with proteinuria compared with patients without proteinuria (p<0.001), indicating that these risk factors contribute to the increased cardiovascular mortality in patients with clinical nephropathy.