Slobodan Peric

Mortality and incidence of renal replacement therapy in people with type 1 diabetes mellitus--a three decade long prospective observational study in the Lainz T1DM cohort.

CONTEXT AND OBJECTIVE We investigated long term mortality, requirement for renal replacement therapy (RRT), and incidence of other late diabetic complications in an observational cohort study of 641 people with type 1 diabetes (T1DM). DESIGN Prospective observational cohort study. SETTING The study was conducted at a Tertiary Diabetes Centre in Vienna, Austria. PATIENTS A cohort with all people with T1DM (n = 641, 47% females, 30 ± 11 years) attending their annual diabetes review was created in 1983-1984. Biomedical data were collected. MAIN OUTCOME MEASURES In 2013 we investigated mortality rates and incidence rates of RRT by record linkage with national registries and incidence of other major diabetes complications by questionnaire. RESULTS 156 (24%) patients died [mortality rate: 922 (95%CI: 778-1066) per 100 000 person years]. Fifty-five (8.6%) received RRT [incidence rate: 335 (95%CI: 246-423) per 100 000 person years]. The 380 questionnaires (78% return rate) recorded cardiac events, strokes, limb amputations, and/or blindness, affecting 21.8% of survivors. Mortality and incidence of RRT increased in each quartile of baseline HbA1c, with the lowest rates in the quartile with HbA1c ≤ 6.5% (48 mmol/mol) (P < .05). CONCLUSIONS In people with established type 1 diabetes who were observed for almost three decades, the overall mortality was 24% and the incidence of renal replacement therapy was 8.6%, with a 21.8% combined incidence rate of the other hard endpoints in the surviving people. A clear linear relationship between early glycemic control and the later development of end stage renal disease and mortality has been found.

High-sensitivity cardiac troponin T in patients with intermittent claudication and its relation with cardiovascular events and all-cause mortality – The CAVASIC Study

BACKGROUND Serum concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are elevated in various diseases. The role of this marker in peripheral arterial disease (PAD) has not been fully investigated. METHODS Hs-cTnT was measured in the CAVASIC Study, a male cohort of 235 patients diagnosed with intermittent claudication and 249 age- and diabetes-matched controls. Patients with symptomatic PAD were prospectively followed for a median time of 7 years. The association of hs-cTnT with PAD, cardiovascular disease (CVD) at baseline as well as incident CVD and all-cause mortality during follow-up was analyzed. RESULTS Detectable hs-cTnT was associated with an 84% higher probability for symptomatic PAD at baseline: OR = 1.84, 95%CI 1.05-3.21, p = 0.03. Inclusion of ln-NT-proBNP or prevalent CVD abolished this association (both OR = 1.22, p = 0.52). However, detectable hs-cTnT was associated with prevalent CVD (n = 69) in PAD patients independent from ln-NT-proBNP: OR = 3.42, p = 0.001. In the adjusted Cox regression analysis detectable (HR = 2.15, p = 0.05) and especially hs-cTnT ≥ 14 ng/L (HR = 5.06, p < 0.001) were predictive for all-cause mortality (n = 39) independent from ln-NT-proBNP. Furthermore, hs-cTnT ≥ 14 ng/L was significantly associated with incident CVD (n = 66): HR = 3.15, 95%CI 1.26-7.89, p = 0.01. CONCLUSIONS This study in male patients with intermittent claudication and age- and diabetes-matched controls revealed hs-cTnT to be associated with PAD and prevalent CVD. The latter association was even significant after considering NT-proBNP. Prospectively, in PAD patients hs-cTnT was predictive for incident cardiovascular diseases and all-cause mortality. Thus, hs-cTnT could be a surrogate marker for cardiomyocyte damage also in symptomatic PAD patients.

Use of Calcium Channel Blockers is Associated with Mortality in Patients with Chronic Kidney Disease

Background/Aims: The use of antihypertensive medicines has been shown to reduce proteinuria, morbidity, and mortality in patients with chronic kidney disease (CKD). A specific recommendation for a class of antihypertensive drugs is not available in this population, despite the pharmacodynamic differences. We have therefore analysed the association between antihypertensive medicines and survival of patients with chronic kidney disease. Methods: Out of 2687 consecutive patients undergoing kidney biopsy a cohort of 606 subjects with retrievable medical therapy was included into the analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy. Main outcome variable was death. Results: Overall 114 (18.7%) patients died. In univariate regression analysis the use of alpha-blockers and calcium channel antagonists, progression of disease, diabetes mellitus (DM) type 1 and 2, arterial hypertension, coronary heart disease, peripheral vascular disease, male sex and age were associated with mortality (all p<0.05). In a multivariate Cox regression model the use of calcium channel blockers (HR 1.89), age (HR 1.04), DM type 1 (HR 8.43) and DM type 2 (HR 2.17) and chronic obstructive pulmonary disease (HR 1.66) were associated with mortality (all p < 0.05). Conclusion: The use of calcium channel blockers but not of other antihypertensive medicines is associated with mortality in primarily GN patients with CKD.

Left ventricular ejection fraction is associated with prevalent and incident cardiovascular disease in patients with intermittent claudication – results from the CAVASIC Study

BACKGROUND Individuals with an impaired ventricular function have a poor prognosis due to underlying heart failure and higher mortality rates. Patients with peripheral arterial disease (PAD) represent a high-risk population for left ventricular systolic dysfunction (LVSD). METHODS The left ventricular ejection fraction (LVEF) was measured in a subset of the CAVASIC Study, consisting of 180 male patients with intermittent claudication and 226 controls. The patients were prospectively followed for a median time of 7 years. The association of LVEF with PAD and prevalent cardiovascular disease (CVD) as well as with incident CVD and survival rates during follow-up was analyzed. RESULTS The prevalence of LVSD (LVEF<55%) was 30% among PAD patients and 7% among controls (p < 0.001). The adjusted logistic regression analysis showed that a decrease of LVEF by one standard deviation (SD) and an LVEF below 55% was associated with PAD (OR = 1.72, 95%CI 1.30-2.28 and OR = 5.71, 95%CI 2.52-12.95, both p < 0.001). Similar results were found for prevalent CVD (n = 50) in PAD patients: LVEF per SD: OR 1.60; LVEF <55%: OR 2.81, both p ≤ 0.008. The adjustment for ln-NT-proBNP or hs-cTnT resulted in a borderline significant association. In the adjusted Cox regression analysis a decrease of LVEF by one SD showed a trend for association with all-cause mortality (n = 32) (HR 1.27, p = 0.08). An impaired LVEF significantly increased the risk for incident major CVD events (n = 52): HR 1.56, p < 0.01. CONCLUSIONS Patients with PAD have significantly lower LVEF values compared to controls. The LVEF can serve as a risk predictor for subsequent cardiovascular disease among this high-risk population.

Growth differentiation factor 15 increases following oral glucose ingestion: effect of meal composition and obesity

OBJECTIVE Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-β superfamily. Increased GDF15 concentrations are associated with insulin resistance, diabetes and obesity. We investigated the physiological effects of meal composition and obesity on the regulation of systemic GDF15 levels. DESIGN Lean (n = 8) and obese (n = 8) individuals received a carbohydrate- or fat-rich meal, a 75 g oral glucose load (OGTT) or short-term fasting. OGTTs were performed in severely obese patients (n = 6) pre- and post-bariatric surgery. METHODS Circulating serum GDF15 concentrations were studied in lean and obese individuals in response to different meals, OGTT or short-term fasting, and in severely obese patients pre- and post-bariatric surgery. Regulation of GDF15 mRNA levels and protein release were evaluated in the human hepatic cell line HepG2. RESULTS GDF15 concentrations steadily decrease during short-term fasting in lean and obese individuals. Carbohydrate- and fat-rich meals do not influence GDF15, whereas an OGTT leads to a late increase in GDF15 levels. The positive effect of OGTT on GDF15 levels is also preserved in severely obese patients, pre- and post-bariatric surgery. We further studied the regulation of GDF15 mRNA levels and protein release in HepG2, finding that glucose and insulin independently stimulate both GDF15 transcription and secretion. CONCLUSION In summary, high glucose and insulin peaks upregulate GDF15 transcription and release. The nutrient-induced increase in GDF15 levels depends on rapid glucose and insulin excursions following fast-digesting carbohydrates, but not on the amount of calories taken in.

No association of angiotensin-converting enzyme inhibitor or angiotensin 2 receptor blocker intake with acute kidney injury in patients undergoing kidney biopsy.

Background: Treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin 2 receptor blockers (ARBs) is associated with an increased risk for acute kidney injury after cardiovascular interventions. However, for patients undergoing kidney biopsy, no data is available. Methods: Four hundred and sixty-six patients undergoing kidney biopsy were retrospectively analyzed of whether or not concomitant intake of ACEIs or ARBs impairs kidney function. Results: Three hundred and twenty-three patients received ACEIs or ARBs or both before kidney biopsy. ACEI/ARB intake had no effect on kidney function compared to patients without this medication (all p > 0.05). Conclusion: Treatment with ACEIs or ARBs is not associated with risk of acute kidney injury in subjects undergoing kidney biopsy.

Kidney biopsy in patients with glomerulonephritis: is the earlier the better?

BackgroundInterventional diagnostic procedures are established for several diseases in medicine. Despite the KDOQI guideline recommendation for histological diagnosis of kidney disease to enable risk stratification, its optimal time point has not been evaluated. We have therefore analyzed whether histological diagnosis of glomerulonephritis (GN) at an early stage of chronic kidney disease (CKD) is associated with different outcome compared to diagnosis at a more advanced stage.MethodsA cohort of 424 consecutive patients with histological diagnosis of GN were included in a retrospective data analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy and after consecutive immunosuppressive therapy. Censored events were death, initiation of dialysis or kidney transplantation, or progression of disease, defined as deterioration of CKD stage ≥1 from kidney biopsy to last available kidney function measurement.ResultsOccurrence of death, dialysis/transplantation or progression of disease were associated with GFR and CKD stage at the time of kidney biopsy (p < 0.001 for all). Patients with CKD stage 1 and 2 at kidney biopsy had fewer endpoints compared to patients with a GFR of <60 ml/min (p < 0.001).ConclusionKidney function at the time point of histological GN diagnosis is associated with clinical outcome, likely due to early initiation of specific drug treatment. This suggests that selection of therapy yields greatest benefit before renal function is impaired in GN.

The fate of patients with intermittent claudication in the 21st century revisited – results from the CAVASIC Study

Patients with intermittent claudication carry a high risk for cardiovascular complications. The TransAtlantic Inter-Society Consensus (TASC) Group estimated a five-year overall mortality of 30% for these patients, the majority dying from cardiovascular causes. We investigated whether this evaluation is still applicable in nowadays patients. We therefore prospectively followed 255 male patients with intermittent claudication from the CAVASIC Study during 7 years for overall mortality, vascular morbidity and mortality and local PAD outcomes. Overall mortality reached 16.1% (n = 41). Most patients died from cancer (n = 20). Half of patients (n = 22; 8.6%) died within the first five years. Incident cardiovascular events were observed among 70 patients (27.5%), 54 (21.2%) during the first five years. Vascular mortality was low with 5.1% (n = 13) for the entire and 3.1% for the first five years of follow-up. Prevalent coronary artery disease did not increase the risk to die from all or vascular causes. PAD symptoms remained stable or improved in the majority of patients (67%). In summary, compared to TASC, the proportion of cardiovascular events did not markedly decrease over the last two decades. Vascular mortality, however, was low among our population. This indicates that nowadays patients more often survive cardiovascular events and a major number dies from cancer.