Proteinuria modifies the effect of systolic blood pressure on total and cardiovascular disease mortality in patients with type 2 diabetes.

OBJECTIVES: Hypertension and proteinuria are major risk factors for cardiovascular disease (CVD) mortality in patients with type 2 diabetes. Blood pressure (BP) targets have been progressively lowered in these patients to prevent or delay the progression of nephropathy. However, no long-term population-based studies have been reported on the interaction between BP and proteinuria with respect to total and CVD mortality in patients with type 2 diabetes. DESIGN: We prospectively followed 881 middle-aged type 2 diabetic patients, free of CVD events at baseline, for up to 18 years. Participants were categorized into four groups according to baseline systolic BP (<130, 130-139, 140-159 and ≥160 mmHg) and further stratified by proteinuria (≤150 or >150 mg L(-1)). Cox proportional hazards model was used to estimate the joint association between systolic BP and proteinuria and the risk of mortality. RESULTS: During follow-up, 607 patients died including 395 because of CVD. After adjustment for confounding factors, total and CVD mortality were significantly higher in patients with proteinuria and systolic BP <130 mmHg compared with those with systolic BP between 130 and 160 mmHg. The prognosis was similar in patients with systolic BP <130 mmHg or ≥160 mmHg. Among patients without proteinuria, systolic BP <130 mmHg was associated with a nonsignificant reduction in mortality. CONCLUSIONS: Type 2 diabetic patients with proteinuria and with systolic BP <130 mmHg may have an increased risk of CVD mortality. The presence of proteinuria should be taken into account when defining the target systolic BP level for the prevention of fatal CVD events in patients with type 2 diabetes.

Kinetics of blood CD34(+) cells after chemotherapy plus G-CSF in poor mobilizers: implications for pre-emptive plerixafor use.

Mobilization and collection of stem cells is difficult in a proportion of patients intended for autologous stem cell transplantation (ASCT). We have evaluated mobilization kinetics of blood CD34(+) cells (B-CD34(+)) to form basis for algorithm to facilitate rational pre-emptive plerixafor use. Altogether 390 chemomobilized patients were included.Forty-three patients (11%) did not reach BCD34+count ≥10×10(6)/l. Mobilization kinetics differed according to the mobilization capacity observed. Among those who were very poor or inadequate mobilizers (peak BCD34(+)count ≤5×10(6)/l and 6­10×10(6)/l, respectively), BCD34+counts rarely rose after white blood cells (WBC) >5­10×10(9)/l, whereas in many standard mobilizers a later rise in CD34(+) counts could be observed. Four algorithms based on WBC and CD34(+) counts were constructed. According to this patient series, algorithm II (WBC >5×109/l and BCD34+≤10×10(6)/l) and algorithm IV (WBC >10×10(9)/l andB-CD34(+) ≤10×10(9)/l) were the most applicable. For algorithm II the sensitivity was 0.97 and specificity 1.00, respectively, to identify patients for plerixafor use provided that all patients with B-CD34+ maximum ≤10×10(6)/l would have needed plerixafor.This simple model needs a prospective validation.

Proteinuria modifies the effects of physical activity on total and cardiovascular disease mortality rates in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Physical activity reduces cardiovascular disease (CVD) and total mortality rates in patients with type 2 diabetes. However, it is not known whether or not the effects of physical activity on mortality rates depend on the presence of proteinuria in type 2 diabetic patients. METHODS: We prospectively followed up 577 patients with type 2 diabetes who were aged 45 to 64 years and were free of CVD at baseline. Participants were stratified according to the presence of proteinuria (300 mg/l) and the degree of physical activity (0-4 metabolic equivalent tasks [MET] or >4 MET). The Cox proportional hazards model was used to estimate the association of physical activity and proteinuria with risk of mortality. RESULTS: During the 18-year follow-up, 356 patients died, of whom 217 died from CVD. Physically more active patients had significantly reduced total, CVD and CHD mortality rates if they did not have proteinuria. In contrast, physically active proteinuric patients had significantly increased total and CVD mortality rates (HR 1.83, 95% CI 1.00-3.36, p=0.049) in univariate analyses, with HR 2.43 (95% CI 1.09-5.40, p=0.030) in multivariate analyses. CONCLUSIONS/INTERPRETATION: Physical activity reduces total and CVD mortality rates in type 2 diabetic patients without proteinuria. However, in proteinuric patients, no protective effect was observed. Larger studies are needed to confirm the latter finding and to define which exercise intensity leads to possible harmful effects.

Risk factors for end-stage renal disease in a community-based population: 26-year follow-up of 25,821 men and women in eastern Finland.

BACKGROUND AND OBJECTIVE: There are very few European cohort studies assessing the risk factors of end-stage renal disease (ESRD) in a community-based population. This study investigated the predictors of ESRD in Finland. DESIGN: Prospective cohort study. SETTING: Eastern Finland. SUBJECTS: A random sample of 25,821 men and women aged 25-64 years from the national population register participating in three independent cross-sectional population surveys in 1972, 1977 and 1982. Only the subjects without diagnosis of ESRD or chronic kidney disease based on the national register data were included in the study. MAIN OUTCOME MEASURE: Initiation of renal replacement therapy (dialysis or kidney transplantation) identified from the Finnish Registry for Kidney Diseases through December 31, 2006. RESULTS: A total of 94 cases with ESRD were identified during a mean follow-up period of 26.5 years. In a multivariate proportional subdistribution hazard regression analysis, taking into account death as a competing risk event, diabetes (hazard ratio [HR] 4.76, 95% confidence interval [CI] 2.32-9.79), hypertension (HR 2.21, 95% CI 1.19-4.12), obesity defined as body mass index > or =30 kg m(-2) (HR 2.02, 95 %CI 1.10-3.71) and male gender (HR 1.68, 95% CI 1.19-4.12) were independent risk factors for ESRD. CONCLUSION: The findings of the present study confirm that modifiable risk factors play a major role in the development of ESRD in the North-European population. People with diabetes, hypertension or obesity should be considered as the target groups when planning preventive measures to control the future epidemic of ESRD.

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study.

AIMS/HYPOTHESIS: AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. SUBJECTS AND METHODS: Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45-64 years. These participants were followed for 18 years for total, CVD and CHD mortality. RESULTS: Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p = 0.002) and CVD mortality (p = 0.021) in women, but not in men. Serum levels of AGEs in the highest sex-specific quartile predicted all-cause (hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14-1.99; p = 0.004), CVD (HR 1.56; 95% CI 1.12-2.19; p = 0.009), and CHD (HR 1.68; 95% CI 1.11-2.52; p = 0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. CONCLUSIONS/INTERPRETATION: Increased serum levels of AGEs predict total and CVD mortality in women with type 2 diabetes.

Proteinuria and metabolic syndrome as predictors of cardiovascular death in non-diabetic and type 2 diabetic men and women.

AIMS/HYPOTHESIS: Proteinuria predicts cardiovascular disease (CVD), but it is unclear whether this is explained by the association of the metabolic syndrome with proteinuria. Therefore, we investigated proteinuria and the metabolic syndrome as independent predictors of CVD death in men and women. METHODS: The cohort comprised 574 non-diabetic men, 707 non-diabetic women, 371 diabetic men and 349 diabetic women, all free of CVD at baseline. Modified World Health Organization criteria were used to define the metabolic syndrome, and a urinary protein concentration of >or=0.1 g/l (or >or=0.2 g/l) to define proteinuria. The endpoint was CVD mortality during the 18-year follow-up. RESULTS: Among non-diabetic men, CVD mortality per 1,000 person-years was as follows: no metabolic syndrome, no urinary protein group: 5.3; no metabolic syndrome, positive for urinary protein: 8.9; positive for metabolic syndrome, no urinary protein: 13.3; and positive for metabolic syndrome and urinary protein: 14.9. For non-diabetic women the corresponding values were: 0.9, 2.3, 4.9 and 7.9, respectively. Among diabetic men, CVD mortality per 1,000 person-years was 15.2, 32.5, 23.6 and 42.0 for the respective groups. Among diabetic women it was 25.3, 38.0, 26.3 and 40.3 (urinary protein in all cases defined as >or=0.1 g/l). In multivariate Cox models including both urinary protein and metabolic syndrome, the hazard ratios (HRs, 95% CI) of proteinuria for CVD mortality were 1.5 (0.9-2.4) in non-diabetic men, 1.8 (0.8-4.2) in non-diabetic women, 1.6 (1.0-2.6) in diabetic men and 1.6 (1.1-2.3) in diabetic women. Urinary protein as a continuous variable was associated with CVD mortality in all groups. The corresponding HRs for metabolic syndrome were: 1.6 (0.9-2.7), 4.0 (1.7-9.7), 1.5 (1.1-2.0) and 1.1 (0.8-1.5). CONCLUSIONS/INTERPRETATION: Proteinuria predicted CVD mortality independently of the presence of metabolic syndrome in non-diabetic and diabetic subjects. Metabolic syndrome predicted CVD mortality in non-diabetic women and in diabetic men, independently of the presence of proteinuria.