Microalbuminuria as Identified by a Spot Morning Urine Specimen in Non-insulin-treated Diabetes: an Eight-year Follow-up Study

This study followed up a cohort of patients with microalbuminuria identified on a spot morning urine sample 8 years earlier and aimed to determine if a spot morning urinary albumin concentration was able to identify patients with non-insulin treated diabetes at increased risk of mortality and progression to nephropathy. In 1984, 47 of 216 patients chosen by random selection from our teaching hospital-based diabetes clinic were identified as having microalbuminuria (urinary albumin concentration 35–300 μg ml^?1). Subjects were compared with an age-matched control group from the 1984 cohort who did not have microalbuminuria. Eight years later, 22 of 47 (46.8 %) patients with microalbuminuria had died compared to 10 of 47 (21.3 %) patients without albuminuria (p < 0.05). The majority of deaths were from cardiovascular disease (53.1 %). Logistic regression showed microalbuminuria to be an independent predictor of mortality, not influenced by age, duration of diabetes, blood pressure, glycosylated haemoglobin or creatinine at the initial examination. Eight years later, in the group with initial microalbuminuria, eight still had microalbuminuria and five patients had developed nephropathy. In the group without albuminuria in 1984, only one patient had progressed to microalbuminuria and no patients to nephropathy. In conclusion, a spot urinary albumin concentration is of value in identifying patients with an increased risk of mortality or progression to nephropathy, and is simple to obtain at a clinic.     

Hyperuricemia and coronary heart disease: A systematic review and meta‐analysis

Objective

The role of serum uric acid as an independent risk factor for cardiovascular disease remains unclear, although hyperuricemia is associated with cardiovascular disease such as coronary heart disease (CHD), stroke, and hypertension.

Methods

A systematic review and meta‐analysis using a random‐effects model was conducted to determine the risk of CHD associated with hyperuricemia in adults. Studies of hyperuricemia and CHD were identified by searching major electronic databases using the medical subject headings and keywords without language restriction (through February 2009). Only prospective cohort studies were included if they had data on CHD incidences or mortalities related to serum uric acid levels in adults.

Results

Twenty‐six eligible studies of 402,997 adults were identified. Hyperuricemia was associated with an increased risk of CHD incidence (unadjusted risk ratio [RR] 1.34, 95% confidence interval [95% CI] 1.19–1.49) and mortality (unadjusted RR 1.46, 95% CI 1.20–1.73). When adjusted for potential confounding, the pooled RR was 1.09 (95% CI 1.03–1.16) for CHD incidence and 1.16 (95% CI 1.01–1.30) for CHD mortality. For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR for CHD mortality was 1.12 (95% CI 1.05–1.19). Subgroup analyses showed no significant association between hyperuricemia and CHD incidence/mortality in men, but an increased risk for CHD mortality in women (RR 1.67, 95% CI 1.30–2.04).

Conclusion

Hyperuricemia may marginally increase the risk of CHD events, independently of traditional CHD risk factors. A more pronounced increased risk for CHD mortality in women should be investigated in future research.     

Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria

Summary In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 of 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p=0.004) with a risk reduction of 69.2% (95% confidence interval (CI): 31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1–83.6%], p=0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1–26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [–18.6–0.4%] per year in the captopril-treated group (p=0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril-treated group (–6.4 [–10.2––2.5] vs –1.4 [–5.3–2.6] ml · min^–1 · 1.73 m^–2, p=0.07). Baseline albumin excretion rate (p<0.0001) and glycated haemoglobin (p=0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p=0.02) and serum cholesterol level (p=0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects.Abbreviations ACE Angiotensin converting enzyme - IDDM insulin-dependent diabetes mellitus - GFR glomerular filtration rate - C captopril - P placebo - AER albumin excretion rate - MAP mean arterial pressure Corresponding author: Professor G.C. Viberti, Unit for Metabolic Medicine, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, Guy's Hospital, London SE1 9RT, UKMembership of the Study Group is listed in the Acknowledgement section     

Assessment of microalbuminuria and glycated hemoglobin in type 2 diabetes mellitus complications

ObjectiveTo relate microalbuminuria with the degree of glycaemic control in type 2 diabetic patients and determine the prevalence of poor glycemic control amongst the normotensive diabetes mellitus (NDM) and hypertensive diabetes mellitus (HDM) with or without microalbuminuria.MethodsA total of 95 type 2 diabetes mellitus patients and 30 healthy controls were randomly selected and studied. 17 of the 95 patients were normotensive diabetic with microalbuminuria, 40 of them were HDM presenting with microalbuminuria and 38 were NDM without microalbuminuria. Their blood was obtained for fasting plasma glucose and glycated haemoglobin while their urine was obtained for albumin and creatinine estimation and the ratio was calculated.ResultsOut of the 95 diabetic patients studied, 57 (60%) of them had microalbuminuria while 38 (40%) had normoalbuminuria. The mean ages in the diabetics with microalbuminuria were higher than those without microalbuminuria (P=0.054 6). The mean glycated haemoglobin was the highest (5.95±2.06)% in NDM with microalbuminuria when compared with HDM with microalbuminuria (5.83±1.62)% and that in (5.66±2.49)% in NDM without microalbuminuria (P=0.000 9). Similarly, fasting plasma glucose was the highest (9.09±4.31) mmol/L in NDM with microalbuminuria than those without microalbuminuria (7.70±3.33) mmol/L (P=0.000 1). The prevalence of poor glycaemic control was the highest (29%) in NDM with microalbuminuria while the least (21%) in NDM without microalbuminuria.ConclusionsThe risk of microalbuminuria increases with poor glycemic control. Persistent increase in glycated haemoglobin may be an indicator of worsening albumin creatinine ratio and diabetic nephropathy. Therefore, regular screening for microalbuminuria in addition to continuous (3-monthly) glycated HbA1c estimation is advised.     

The Natural Course of Microalbuminuria in Insulin-dependent Diabetes: A 10-year Prospective Study

The purpose of this study was to describe the clinical course in patients followed right from the onset of microalbuminuria to the development of diabetic nephropathy. A 10-year prospective follow-up of 209 consecutive normotensive insulin-dependent diabetic patients with normal urinary albumin excretion (UAE <30 mg 24 h^?1), age 34 (18–50) years and duration of diabetes 17 (10–30) years was performed. Twenty-four-hour urinary albumin excretion was measured every 4 months, glycated haemoglobin and supine blood pressure was measured annually. Two-hundred (96%) patients completed 10 (range 5–10) years follow-up. Twenty-nine (15%) patients developed persistent microalbuminuria (UAE 30–300 mg 24 h^?1). Eight of these have progressed to nephropathy and one had died of diabetic nephropathy. Multiple stepwise logistic regression analysis demonstrated baseline urinary albumin excretion (p = 0.0016) and glycated haemoglobin (p = 0.0014) but not blood pressure as predictors of development of microalbuminuria within the following 10 years. The median annual increase in urinary albumin excretion was 27 (range 17–65)% in the 29 patients developing microalbuminuria. The median duration from onset of microalbuminuria to development of nephropathy was 7 years. The prevalence of patients receiving antihypertensive treatment (BP > 140/90 mmHg) increased from 10% at onset of microalbuminuria to 45% 4 years after onset of microalbuminuria. The prevalence of patients with proliferative retinopathy increased from 7% at onset of microalbuminuria to 28% 4 years after onset of microalbuminuria. The incidence of persistent microalbuminuria in normotensive insulin-dependent diabetic patients is 2% per year, and development of persistent microalbuminuria is a strong predictor of overt nephropathy. Development of hypertension is frequent in the early course of microalbuminuria and treatment modalities for normotensive patients with microalbuminuria are urgently needed.     

Increased plasma glycated low-density lipoprotein concentrations in diabetes: a marker of atherogenic risk

Nonenzymatic glycation of apolipoprotein B in the low-density lipoprotein (LDL) complex has been considered a proatherogenic modification contributory to the increased susceptibility of patients with diabetes to atherosclerosis. We postulated that glycated LDL concentrations might be associated with other markers of cardiovascular disease. To explore this hypothesis, we measured glycated LDL concentrations by a monospecific immunoassay in 50 patients with type 1 and 100 patients with type 2 diabetes and examined relationships with the amount of albumin excretion and the serum cholesterol and triglyercide concentrations. Plasma glycated LDL showed a significant positive correlation (r = 0.325; P < 0.001) with urinary albumin excretion that was higher in type 1 (r = 0.463) than in type 2 (r = 0.245) patients. The mean glycated LDL concentration progressively increased with increasing albumin excretion when patients were subcategorized into groups of normoalbuminuria, low (相似文献   

Microalbuminuria and mortality in individuals with coronary heart disease: A meta-analysis of a prospective study

AimMicroalbuminuria has been elevated as an outcome predictor in cardiovascular medicine. However, due to the small number of studies investigating the association of microalbuminuria and mortality in the coronary heart disease (CHD) population, the prognosis value of microalbuminuria in CHD remains under debate. The objective of this meta-analysis was to investigate the relationship between microalbuminuria and mortality in individuals with CHD.MethodA comprehensive literature search was performed using Pubmed, EuroPMC, Science Direct, and Google Scholar from 2000 to September 2022. Only prospective studies investigating microalbuminuria and mortality in CHD patients were selected. The pooled effect estimate was reported as risk ratio (RR).Results5176 patients from eight prospective observational studies were included in this meta-analysis. Individuals with CHD have a greater overall risk of all-cause mortality (ACM) [rR = 2.07 (95% CI = 1.70–2.44); p = 0.0003; I² = 0.0%] as well as cardiovascular mortality (CVM) [rR = 3.23 (95% CI = 2.06–4.39), p < 0.0001; I² = 0.0%]. Subgroup analysis based on follow-up duration and a subset of CHD patients were similarly associated with an increased risk of ACM.ConclusionThis meta-analysis indicates that microalbuminuria is associated with a higher risk of mortality in individuals with CHD. Microalbuminuria can serve as a predictor of poor outcomes in CHD patients.     

Prospective study of development of microalbuminuria and retinopathy in Brazilian IDDM patients

With the aim to study potential risk factors for the development of microalbuminuria and retinopathy, baseline characteristics were examined in 50 Brazilian IDDM patients folowed for 4.48 years with a 2-year reexamination. During the study, 3 patients (6%) aged 25.9 ± 4.4 years, duration of diabetes 8.1 ± 4.2 years, died from acute complications without microalbuminuria and retinopathy after a follow-up of 2.1 ± 0.7 years. The standardized mortality rate for the group was 0.84 per 1000 (95% CL, 0.31, 1.83) in comparison to 0.14 per 1000 in the general population. From 34 normoalbuminuric individuals ate baseline (urinary albumin excretion rate (AER) ≤ 20 μg/min in ≥ 2 overnight urine collections), 10 developed microalbuminuria with an incidence density of 6.5 cases per 100 person-years (95%CL, 2.23, 10.16). Spontaneous normalization of AER was found in 2 of 4 patients with microalbuminuria at cycle 2. Multiple stepwise regression analysis demonstrated that baseline AET (p = 0.03), but not glycated hemoglobin, blood pressure or duration of diabetes, predicted end-of-study AER. From 36 patients without retinopathy, 10 developed nonproliferative retinopathy with an incidence density of 6.6 cases per 100 person-years (95%CL, 2.85, 10.54). Retinopathy was associated with duration (p = 0.05) and age at diagnosis of diabetes (p = 0.01). A tendency with baseline AER (p = 0.06) was also noted. No patient developed macroalbuminuria, proliferative retinopathy or hypertension. By the end of our study, in a cohort of young IDDM patients followed in a developing country, 6% died from acute complications and 15 patients (44.1%) developed retinopathy and/or microalbuminuria. Our results suggest that the only predictor of end-of-study AER was baseline AER. Also, duration of diabetes and age at diagnosis appear to be risk factors for retinopathy. Received: 22 May 1999 / Accepted in revised form: 3 March 2000     

Persistent albuminuria as a surrogate marker of chronic kidney damage among newly diagnosed hypertensives: Prevalence and risk factors in an urban population in Karachi,Pakistan

Background: Hypertension is a major public health problem worldwide and a key factor for chronic kidney disease (CKD). Detection and treatment of CKD is of paramount importance. Albuminuria is one of the earliest screening markers recommended in patients at increased risk for CKD. Objective: We conducted this study to determine the prevalence of persistent albuminuria (PA) in newly diagnosed hypertensive subjects and to study its associated risk factors. Methods: A total of 173 (72%) of 240 subjects among 1340 newly diagnosed hypertensive subjects from an ongoing community-based cohort study who had been screened once for the presence of albuminuria were retested for the presence of PA in this study. Urinary albumin concentration (UAC) in mg/L and albumin-to-creatinine ratio (ACR) in mg/g creatinine were determined in a spot morning urine sample by nephelometry. Results: The prevalence of PA signifying CKD was 9.3% with 95% confidence interval (CI) of 7.8–10.8% by UAC and 8.1% by ACR method (95% CI: 6.6–8.4%). Subjects with PA had mean age of 56.4 ± 11.4 years and 50% were males. Factors independently associated were male gender (odds ratio [OR], 1.92 (95% CI: 1.24–2.97)) and age less than 55 years with positive family history of kidney disease (OR, 15.51; 95% CI: 7.35–32.97). Among measurable variables, high cholesterol levels (p = 0.001), and progressively higher levels of systolic blood pressure (p < 0.001) were associated with risk of PA. Conclusion: Hypertensive kidney damage is already present in a significant number of newly diagnosed hypertensives suggesting late detection of hypertension.     

Prospective study of alcohol consumption in the United States: quantity, frequency, and cause-specific mortality

Background: Alcohol average volume (quantity multiplied by frequency) has been associated with mortality in drinkers. However, average volume may mask associations due to quantity or frequency alone. Methods: We prospectively assessed relationships between alcohol quantity and frequency, and mortality from all‐causes, cardiovascular disease, cancer, and other‐causes in a cohort created by linking the 1988 National Health Interview Survey (response rate 87%) to the National Death Index through 2002. Participants were 20,765 current drinkers age ≥ 18 years. At 14‐year follow‐up 2,547 had died. Results: For quantity, among men who consumed ≥5 drinks (compared to 1 drink) on drinking days, adjusted relative risks (RR) of mortality were: for cardiovascular disease, 1.30 [95% confidence interval (CI) 0.96–1.75; p for linear trend (p‐trend) = 0.0295], for cancer, 1.53 (95% CI 1.11–2.09; p‐trend = 0.0026), and for other‐causes, 1.42 (95% CI 1.08–1.87; p‐trend = 0.0029); among women for other‐causes, 2.88 (95% CI 1.61–5.12; p‐trend = 0.0010). For frequency, among men in the highest frequency quartile (compared to the lowest), RR were: for cardiovascular disease, 0.79 (95% CI 0.63–0.99; p‐trend = 0.0330), for cancer, 1.23 (95% CI 0.95–1.59; p‐trend = 0.0461), and for other‐causes, 1.30 (95% CI 1.01–1.67; p‐trend = 0.0070); among women, for cancer, 1.65 (95% CI 1.12–2.45, p‐trend = 0.0031). Average volume obscured effects of quantity alone and frequency alone, particularly for cardiovascular disease in men where quantity and frequency trended in opposite directions. Conclusions: Alcohol quantity and frequency were independently associated with cause‐specific mortality. Accumulating evidence of their differential effects may, in the future, be useful for clinical and public health recommendations.     

Risk factors for primary prevention of cardiovascular disease and risk reduction by lipid control: the OMEGA study risk factor sub-analysis

To identify risk factors for cardiovascular disease (CVD) in hypertensive patients with no history of CVD being treated with antihypertensive drugs, we examined subgroup data (n?=?13?052) from the prospective, observational Olmesartan Mega Study to Determine the Relationship between Cardiovascular Endpoints and Blood Pressure Goal Achievement (OMEGA) study. Risk factors for CVD, stroke and coronary heart disease (CHD) were examined using a Cox proportional hazards model. In addition, the effect of statin therapy at baseline on CHD prevention was analyzed in dyslipidemic patients. The factors significantly related to CVD were female (hazard ratio [HR]?=?0.637, 95% confidence interval [CI] 0.428–0.948), older age (65–69 years: HR?=?2.165, 95% CI 1.214–3.861; 70–74 years: HR?=?2.324, 95% CI 1.294–4.174; ≥75 years: HR?=?2.448, 95% CI 1.309–4.578), family history of CHD (HR?=?1.993, 95% CI 1.249–3.179), diabetes (HR?=?2.287, 95% CI 1.700–3.078), current smoking (HR?=?2.289, 95% CI 1.512–3.466) and alcohol drinking socially (HR?=?0.589, 95% CI 0.379–0.913). Diabetes was a risk factor for both stroke and CHD, while age, family history of CHD, and sodium intake score were risk factors for stroke alone. Sex, dyslipidemia, smoking and exercise habits were risk factors for CHD alone. The risk of CHD in dyslipidemic patients on statin treatment was comparable to the risk in patients without dyslipidemia (HR?=?1.134, 95% CI 0.604–2.126). However, in dyslipidemic patients not on statin treatment, the HR increased to 1.807 (95% CI 1.156–2.825). In conclusion, some risk factors for CVD in hypertensive patients being treated with antihypertensive drugs with no history of CVD differed between CHD and stroke. These results suggest the importance of managing dyslipidemia with a statin for primary prevention of CHD, as well as the importance of hypertension therapy.     

Prothrombotic and Antithrombotic Factors are Elevated in Patients with Type 1 Diabetes Complicated by Microalbuminuria

Increased urinary albumin loss in patients with Type 1 diabetes is associated with accelerated atherosclerosis. Prothrombotic factors known to be associated with cerebrovascular and coronary artery disease in the general population, and antithrombotic factors, were studied in 52 patients with Type 1 diabetes and varying urinary albumin loss and 24 non-diabetic control subjects. Fibrinogen increased from 2.5 g I_-1 (95 % confidence interval 2.3–2.8) in control subjects and 2.8 g I_-1 (2.6–3.0) in diabetic patients without microalbuminuria to 3.1 g I_-1 (2.7–3.5) with microalbuminuria (p < 0.005 vs control; p < 0.001 vs without microalbuminuria). Factor VIIc increased from 81 % (75–86 % in non-diabetic control subjects and 84 % (78–90 %) in diabetic patients without microalbuminuria to 103 % (89–117 %) with microalbuminuria (p < 0.005 vs control; p < 0.05 vs without microalbuminuria) and 118% (86–150%) with albuminuria (p < 0.005 vs control and p < 0.001 vs without microalbuminuria). Levels of the antithrombotic factors protein C, protein S, and antithrombin III also rose in the diabetic patients with evidence of renal damage. Elevation of prothrombotic factors has been associated with increased risk of microvascular disease, whereas elevation of antithrombotic factors has no known protective effect. Therefore, this pattern of alteration of haemostatic factors in diabetic renal disease may contribute to the increased risk of vascular disease associated with both microalbuminuria and albuminuria.     

Association between serum C-reactive protein levels and microalbuminuria: a population-based cross-sectional study in northern Iwate, Japan

OBJECTIVE: The presence of microalbuminuria is a renal marker of vascular endothelial damage, and is an independent and strong predictor of increased risk for cardiovascular mortality and morbidity. Elevated circulating C-reactive protein (CRP) levels have recently been reported to be a novel cardiovascular risk factor, and it has been suggested that this acute-phase protein impairs vascular endothelial function. The aim of the present study was to determine whether serum CRP level is a dependent or an independent risk factor of microalbuminuria in the general population. METHODS: Subjects of this cross-sectional study were apparently healthy individuals drawn from the general Japanese population (mean age, 62; men, 2,236; women, 4,217). Serum CRP levels were determined using a highly sensitive kit and urine albumin-creatinine ratio (UACR) was calculated using a single urine sample. Multivariate logistic regression analysis was used to determine which risk factors (ie, age, hypertension, diabetes, obesity, hypercholesterolemia, smoking, and CRP) might predict the presence of microalbuminuria. RESULTS: In addition to classical cardiovascular risk factors such as age, hypertension, diabetes and obesity, serum CRP levels are also significantly correlated with microalbuminuria in men (odds ratio = 1.42, 95% CI = 1.13-1.79; p < 0.01) and women (odds ratio = 1.25, 95% CI = 1.05-1.49; p < 0.01). When subjects with diabetes were excluded from the analysis, serum CRP levels continued to be a significant predictor for microalbuminuria (odds ratio = 1.35, 95% CI = 1.06-1.73; p < 0.05 for men: odds ratio = 1.23, 95% CI = 1.03-1.47; p < 0.05 for women). CONCLUSIONS: The present study has shown that low-grade inflammation as represented by high sensitivity CRP levels may be significantly related to the presence of microalbuminuria. This suggests that microalbuminuria may be a useful marker representing systemic low-grade inflammation as well as being an established cardiovascular risk factor in apparently healthy individuals.     

Increase in serum prorenin precedes onset of microalbuminuria in patients with insulin-dependent diabetes mellitus

Abstract Aims/hypothesis. The renin-angiotensin system is possibly involved in the pathogenesis of diabetic nephropathy. The most striking change in renin-angiotensin system components in blood of patients with diabetic nephropathy is an increased prorenin concentration. We investigated prospectively serum concentrations of renin-angiotensin system components and the time course of prorenin increase in normoalbuminuric diabetic patients developing microalbuminuria. Methods. Patients (n = 199) with Type I (insulin-dependent) diabetes mellitus and normoalbuminuria at baseline were prospectively followed for 10 years. The prorenin concentrations and other variables possibly associated with the occurrence of microalbuminuria, were investigated by Cox-regression analysis. Results. Of the patients 29 developed microalbuminuria. Glycated haemoglobin values were higher at baseline in these patients. Serum prorenin was similar at baseline but rose in the 29 patients before the development of microalbuminuria and was stable in patients with stable albumin excretion. Renin, angiotensinogen and angiotensin converting enzyme serum concentrations were stable in both groups. Prorenin and glycated haemoglobin were independent prognostic factors for the development of microalbuminuria. A prognostic index, based on these variables, was constructed to estimate the relative risk of developing microalbuminuria. Conclusions/interpretation. Increase in serum prorenin precedes onset of microalbuminuria in normotensive patients with insulin-dependent diabetes mellitus. High concentrations of prorenin in combination with high values of glycated haemoglobin can be used as a predictor of development of microalbuminuria. [Diabetologia (1999) 42: 1006–1010] Received: 30 December 1998 and in revised form: 1 April 1999     

Risk factors for mortality in Type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4

Summary To test the hypothesis that interaction between genetic, immunological, clinical and metabolic risk factors influences the outcome of Type II (non-insulin-dependent) diabetes mellitus, we examined which of the above factors present at baseline were associated with mortality in 134 Type II diabetic patients followed for 9 years. Thirty-eight patients (29 %) died during the follow-up period; the majority of whom (68 %) died from cardiovascular disease. At baseline, the deceased patients had higher HbA_{1 c} values (p = 0.002), higher LDL-triglycerides (p = 0.007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty acid (NEFA) concentrations (p = 0.014), and higher albumin excretion rate (p < 0.0001) than the patients who survived. In addition, the frequency of HLA-DR4 (21 vs 39 %, p = 0.048) and of parietal cell antibodies (5 vs 14 %, p = 0.016) were decreased in the deceased as compared to the living patients. Patients who died during follow-up also had more retinopathy (42 vs 16 %, p = 0.002), neuropathy (57 vs 23 %, p < 0.001), microalbuminuria (45 vs 6 %, p < 0.0001), coronary heart disease (50 vs 13 %, p < 0.0001), and peripheral vascular disease (27 vs 9 %, p = 0.005) at baseline than patients who survived. In a multiple logistic regression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007), HbA_{1 c} (p = 0.018) and albumin excretion rate (p = 0.016) were independent risk factors for death. In patients free of cardiovascular disease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent development of cardiovascular disease. In conclusion, in addition to coexisting macroangiopathy, increased albumin excretion rate, poor glycaemic control and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of autoimmunity may be associated with decreased risk of cardiovascular disease. [Diabetologia (1998) 41: 1253–1262] Received: 29 December 1997 and in revised form: 27 April 1998     

Mortality and morbidity in relation to changes in albuminuria,glucose status and systolic blood pressure: an analysis of the ONTARGET and TRANSCEND studies

Aims/hypothesis

Urinary albumin excretion is a strong predictor of cardiovascular disease. It is uncertain whether improvement from microalbuminuria or deterioration from normoalbuminuria over time in patients with differing changes in glucose and BP change their cardiovascular risk.

Methods

Data on mortality, cardiovascular and renal outcomes were analysed in 22,984 patients from two large parallel randomised clinical trials followed for 56 months. A central laboratory analysed first morning spot urine samples at baseline and after 24 months, and events were recorded over the subsequent 32 months. Patients were stratified by changes in albuminuria, glucose status and mean systolic BP over 2 years.

Results

There was a strong association between albuminuria status and all-cause and cardiovascular mortality and combined cardiovascular and renal endpoints (all p?p?=?0.0004).

Conclusions/interpretation

Patients who showed improvement to normoalbuminuria over 2 years were at lower risk of all-cause and cardiovascular mortality and of cardiovascular and renal events than those who deteriorated to microalbuminuria over time. Albuminuria over time was significantly better than glucose status and BP control in predicting mortality and both cardiovascular and renal outcomes in patients at a high cardiovascular risk.     

Haemostatic Measures in Type 2 Diabetic Patients with Microalbuminuria

The major cause of disability and early mortality in Type 2 diabetes is cardiovascular disease. An enhanced urinary albumin excretion is strongly predictive of increased mortality, but the causal relationship behind this association is unclear. Abnormalities in the haemostatic system may be involved in the vascular pathology. We therefore studied the level of von Willebrand factor (vWf:Ag), factor VIII (VIII:Ag), fibrinogen, and fibronectin in male diabetic patients 50–70 years of age, with normal albumin excretion (n = 14), microalbuminuria (n = 14), and frank albuminuria (n = 7). Fourteen healthy age-matched males served as a reference group. There were no significant differences between normo-and micro-albuminuric patients but vWf:Ag (p < 0.01), VIII:Ag (p < 0.01), and fibrinogen (p < 0.05) were increased in those with frank albuminuria. Urinary albumin excretion rate was significantly correlated to vWf:Ag (r = 0.46, p = 0.005), VIII:Ag (r = 0.45, p = 0.007), and fibrinogen (r = 0.49, p = 0.003). The known duration of diabetes was correlated to vWf and F VIII. The increased level of vWf:Ag in Type 2 diabetes and the significant association to the urinary albumin excretion rate may suggest a linkage between albuminuria and cardiovascular disease. However, the present study demonstrated no increase in haemostatic variables in patients with microalbuminuria as compared with those with normal albumin excretion.     

Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men

Background and objectives

Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.

Design, setting, participants, & measurements

This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997–2001; median follow-up 8.1 years; end of follow-up, 2008).

Results

During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C–based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m²), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m²), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).

Conclusions

These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.     

The combined effect of blood pressure and C-reactive protein with the risk of mortality from coronary heart and cardiovascular diseases

Background and aimsBoth blood pressure and C-reactive protein (CRP) are individually associated with cardiovascular mortality risk. However, the combined effect of systolic blood pressure (SBP) and CRP on coronary heart disease (CHD) and cardiovascular disease (CVD) mortality risk, has not been studied.Methods and resultsWe evaluated the joint impact of SBP and CRP and the risk of mortality in the Kuopio Ischemic Heart Disease prospective cohort study of 1622 men aged 42–61 years at recruitment with no history of CVD. SBP and CRP were measured. SBP was categorized as low and high (cut-off 135 mmHg) and CRP as low and high (cut-off 1.54 mg/L) based on ROC curves. Multivariable adjusted hazard ratios (HRs) with confidence intervals (CI) were calculated.During a median follow-up of 28 years, 196 cases of CHD and 320 cases of CVD deaths occurred. Elevated SBP (>135 mmHg) combined with elevated (CRP >1.54 mg/L) were associated with CHD and CVD mortality (HR 3.41, 95% CI, 2.20–5.28, p < 0.001) and (HR 2.93, 95% CI, 2.11–4.06, p < 0.001) respectively after adjustment for age, examination year, smoking, alcohol consumption, BMI, Type 2 diabetes, energy expenditure, total cholesterol, serum HDL cholesterol, antihypertensive medication and use of aspirin.ConclusionThe combined effect of both high systolic blood pressure and high CRP is associated with increased risk of future CHD and CVD mortality as compared with both low SBP and low CRP levels in general male Caucasian population.     

Clinical utility of haematological inflammatory biomarkers in predicting 30-day mortality in hospitalised adult patients with COVID-19

Coronavirus disease 2019 (COVID-19) is a multisystem disease affecting respiratory, cardiovascular, gastrointestinal, neurological, immunological and haematological systems. The most important indices that have been studied are platelet (PLT) indices in addition to the PLT count and red blood cell distribution width (RDW). This retrospective study included 95 patients with COVID-19 and was conducted at the Hospital Isolation, Scientific and Medical Research Centre and Clinical Pathology Department at Zagazig University Hospitals, Egypt over 6 months from March to August 2021. All patients on admission had a full blood count, which included white blood cell (WBC) count, haemoglobin, RDW, PLT count and its indices in addition to PLT-to-WBC ratio (PWR) and PLT-to-lymphocyte ratio (PLR), which were calculated for all the study patients. There were significant linear correlations for higher levels of the PLR, PWR and RDW and mortality rate (p = 0.03, p < 0.001 and p < 0.001 respectively). Moreover, on multivariable analysis the RDW, PLT count and PWR levels were independent prognostic predictors for mortality with a hazard ratio [HR] of 1.25 (95% confidence interval [CI] 1.09–1.44, p = 0.002), 1.00 (95% CI 0.99–1.00, p = 0.03) and 2.3 (95% CI 1.21–4.48, p = 0.01) respectively. The RDW and PLT indices are accessible predictors that can be valuable prognostic factors for survival assessment and risk stratification of COVID-19.