Gilles Diercks

Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population

Background—For the general population, the clinical relevance of an increased urinary albumin excretion rate is still debated. Therefore, we examined the relationship between urinary albumin excretion and all-cause mortality and mortality caused by cardiovascular (CV) disease and non-CV disease in the general population. Methods and Results—In the period 1997 to 1998, all inhabitants of the city of Groningen, the Netherlands, aged between 28 and 75 years (n=85 421) were sent a postal questionnaire collecting information about risk factors for CV disease and CV morbidity and a vial to collect an early morning urine sample for measurement of urinary albumin concentration (UAC). The vital status of the cohort was subsequently obtained from the municipal register, and the cause of death was obtained from the Central Bureau of Statistics. Of these 85 421 subjects, 40 856 (47.8%) responded, and 40 548 could be included in the analysis. During a median follow-up period of 961 days (maximum 1139 days), 516 deaths with known cause were recorded. We found a positive dose-response relationship between increasing UAC and mortality. A higher UAC increased the risk of both CV and non-CV death after adjustment for other well-recognized CV risk factors, with the increase being significantly higher for CV mortality than for non-CV mortality (P =0.014). A 2-fold increase in UAC was associated with a relative risk of 1.29 for CV mortality (95% CI 1.18 to 1.40) and 1.12 (95% CI 1.04 to 1.21) for non-CV mortality. Conclusions—Urinary albumin excretion is a predictor of all-cause mortality in the general population. The excess risk was more attributable to death from CV causes, independent of the effects of other CV risk factors, and the relationship was already apparent at levels of albuminuria currently considered to be normal.

Thrombus aspiration during primary percutaneous coronary intervention.

BACKGROUND Primary percutaneous coronary intervention (PCI) is effective in opening the infarct-related artery in patients with myocardial infarction with ST-segment elevation. However, the embolization of atherothrombotic debris induces microvascular obstruction and diminishes myocardial reperfusion. METHODS We performed a randomized trial assessing whether manual aspiration was superior to conventional treatment during primary PCI. A total of 1071 patients were randomly assigned to the thrombus-aspiration group or the conventional-PCI group before undergoing coronary angiography. Aspiration was considered to be successful if there was histopathological evidence of atherothrombotic material. We assessed angiographic and electrocardiographic signs of myocardial reperfusion, as well as clinical outcome. The primary end point was a myocardial blush grade of 0 or 1 (defined as absent or minimal myocardial reperfusion, respectively). RESULTS A myocardial blush grade of 0 or 1 occurred in 17.1% of the patients in the thrombus-aspiration group and in 26.3% of those in the conventional-PCI group (P<0.001). Complete resolution of ST-segment elevation occurred in 56.6% and 44.2% of patients, respectively (P<0.001). The benefit did not show heterogeneity among the baseline levels of the prespecified covariates. At 30 days, the rate of death in patients with a myocardial blush grade of 0 or 1, 2, and 3 was 5.2%, 2.9%, and 1.0%, respectively (P=0.003), and the rate of adverse events was 14.1%, 8.8%, and 4.2%, respectively (P<0.001). Histopathological examination confirmed successful aspiration in 72.9% of patients. CONCLUSIONS Thrombus aspiration is applicable in a large majority of patients with myocardial infarction with ST-segment elevation, and it results in better reperfusion and clinical outcomes than conventional PCI, irrespective of clinical and angiographic characteristics at baseline. (Current Controlled Trials number, ISRCTN16716833.)

Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study

BACKGROUND Percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction can be complicated by spontaneous or angioplasty-induced embolisation of atherothrombotic material. Distal blockage induces microvascular obstruction and can result in less than optimum reperfusion of viable myocardium. The Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) found that thrombus aspiration resulted in improved myocardial reperfusion compared with conventional PCI, but whether this benefit improves clinical outcome is unknown. We aimed to investigate whether the early efficacy of thrombus aspiration seen in TAPAS translated into clinical benefit after 1 year. METHODS Patients with ST-elevation myocardial infarction enrolled at the University Medical Centre Groningen were randomly assigned in a 1:1 ratio to either thrombus aspiration or conventional treatment, before undergoing initial coronary angiography. Exclusion criteria were rescue PCI after thrombolysis and known existence of a concomitant disease with life expectancy less than 6 months. Of the 1071 patients enrolled between January, 2005, and December, 2006, vital status at or beyond 1 year after randomisation was available for 1060 (99%). The primary endpoint was cardiac death or non-fatal reinfarction after 1 year, and analysis was by intention to treat. The TAPAS trial is registered with Current Controlled Trials number ISRCTN16716833. FINDINGS Cardiac death at 1 year was 3.6% (19 of 535 patients) in the thrombus aspiration group and 6.7% (36 of 536) in the conventional PCI group (hazard ratio [HR] 1.93; 95% CI 1.11-3.37; p=0.020). 1-year cardiac death or non-fatal reinfarction occurred in 5.6% (30 of 535) of patients in the thrombus aspiration group and 9.9% (53 of 536) of patients in the conventional PCI group (HR 1.81; 95% CI 1.16-2.84; p=0.009). INTERPRETATION Compared with conventional PCI, thrombus aspiration before stenting of the infarcted artery seems to improve the 1-year clinical outcome after PCI for ST-elevation myocardial infarction.

Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity

Abstract. Hillege HL, Janssen WMT, Bak AAA, Diercks GFH, Grobbee DE, Crijns HJGM, van Gilst WH, de Zeeuw D, de Jong PE for the PREVEND Study group (University of Groningen and University Hospital Groningen, Groningen; University Medical centre, Utrecht, the Netherlands). Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med 2001; 249: 519–526.

Effects of Fosinopril and Pravastatin on Cardiovascular Events in Subjects With Microalbuminuria

Background—Microalbuminuria is associated with increased risk of cardiovascular events. We assessed whether therapeutic intervention aimed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects (15 to 300 mg/24 hours). Methods and Results—From the Prevention of Renal and Vascular Endstage Disease (PREVEND) cohort (n=8592), 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial (PREVEND IT). Of these subjects, 864 were randomized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo. The mean follow-up was 46 months, and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity. Mean age was 51±12 years; 65% of subjects were male, and 3.4% had a previous cardiovascular event. Mean cholesterol level was 5.8±1.0 mmol/L, mean systolic/diastolic blood pressure was 130±18/76±10 mm Hg, and median urinary albumin excretion was 22.8 (15.8 to 41.3) mg/24 hours. The primary end point occurred in 45 subjects (5.2%). Fosinopril reduced urinary albumin excretion by 26% (P<0.001). Subjects treated with fosinopril showed a 40% lower incidence of the primary end point (hazard ratio 0.60 [95% CI 0.33 to 1.10], P=0.098, log-rank). Pravastatin did not reduce urinary albumin excretion, and subjects treated with pravastatin showed a 13% lower incidence of the primary end point than subjects in the placebo group (0.87 [0.49 to 1.57], P=0.649, log-rank). Conclusions—In microalbuminuric subjects, treatment with fosinopril had a significant effect on urinary albumin excretion. In addition, fosinopril treatment was associated with a trend in reducing cardiovascular events. Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events.

Incidence and clinical consequences of distal embolization on the coronary angiogram after percutaneous coronary intervention for ST-elevation myocardial infarction

AIMS We investigated the incidence and sequelae of angiographically visible distal embolization (AVDE) after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction patients treated with aspirin, heparin, clopidogrel, and glycoprotein-IIb/IIIa inhibitors. METHODS AND RESULTS As part of TAPAS, AVDE was a predefined secondary endpoint. We compared angiographic and clinical characteristics, and outcomes of patients with and without AVDE after PCI. AVDE was present on 6.3% of 883 post-procedural angiograms. Angiographically visible distal embolization was associated with significantly worse outcomes, as expressed by lower myocardial blush grade, impaired ST-segment resolution, and higher enzyme levels (all P </= 0.001). Mortality 1 year after PCI was 4 of 56 (7.1%) in patients with AVDE and 43 of 827 (5.2%) in patients without AVDE (P= ns), re-infarction occurred in 5 of 56 (8.9%), and 25 of 827 (3.0%) patients (P = 0.018). The thrombus aspirate more often contained erythrocytes in patients with AVDE than in patients without AVDE (50.0% vs. 15.7%, P < 0.001), and the size of the aspirated thrombus was larger in patients with AVDE (P = 0.002). CONCLUSION In patients with triple anti-platelet therapy, the incidence of AVDE after PCI is low, compared with previous reports. Nevertheless, AVDE is associated with impaired myocardial reperfusion and poor outcome. Thrombus composition and size are related to AVDE after PCI.

Rationale, design, and baseline characteristics of a trial of prevention of cardiovascular and renal disease with fosinopril and pravastatin in nonhypertensive, nonhypercholesterolemic subjects with microalbuminuria (the prevention of REnal and vascular ENdstage disease intervention trial [PREVEND IT])

This study describes the rationale, design, and baseline characteristics of a trial to determine whether treatment with fosinopril 20 mg/day and/or pravastatin 40 mg/ day will prevent cardiovascular and renal disease in nonhypertensive (RR <160/100 mm Hg and not using antihypertensive medication) and nonhypercholesterolemic (total cholesterol <8.0 or <5.0 mmol/L in case of previous myocardial infarction and not using lipid lowering medication) men and women with persistent microalbuminuria (urinary albumin excretion >10 mg/L once in an early morning spot urine and 15 to 300 mg/24-hour at least once in two 24-hour urine collections). The Prevention of REnal and Vascular ENdstage Disease Intervention Trial is a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design. The 864 randomized subjects will be monitored for a minimum of 4 years and a maximum of 5 years. The primary efficacy parameter is defined as the combined incidence of all-cause mortality or hospital admission for documented (1) nonfatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease.

The many faces of epidermolysis bullosa acquisita after serration pattern analysis by direct immunofluorescence microscopy

Background  The inflammatory variant of epidermolysis bullosa may mimic a form of pemphigoid.

Microalbuminuria modifies the mortality risk associated with electrocardiographic ST-T segment changes

OBJECTIVES We sought to investigate whether microalbuminuria, a proposed marker of generalized vascular damage, enhances the prognostic value of ST-T segment changes for all-cause and cardiovascular mortality in the general population. BACKGROUND ST-T segment changes on the rest electrocardiogram (ECG) predict mortality in the general population. However, the excess risk seems to be low, particularly in nonhospitalized populations with a low cardiovascular risk profile. METHODS In a population of 7,330 male and female subjects, a total of 89 deaths (1.2%) occurred during a median three-year follow-up. In 69 of these, the cause of death was obtained from the Central Bureau of Statistics: 25 subjects died of cardiovascular causes (36%). Using computerized Minnesota coding, ST-T segment changes were coded as 4.1-4 and 5.1-4. Microalbuminuria was defined as a urinary albumin excretion of 30 to 300 mg per 24 h. RESULTS The combination of ST-T segment changes and microalbuminuria showed a higher hazard ratio (HR) for all-cause mortality (HR 8.6 [95% confidence interval [CI] 4.8 to 15.2, p < 0.0001), as compared with ST-T segment changes in the absence of microalbuminuria (HR 1.3 [95% CI 0.7 to 2.5]), which was independent of other cardiovascular risk factors (HR 3.3 [95% CI 1.5 to 7.1], p = 0.002). The combination showed a higher HR when only cardiovascular deaths were taken into account, as compared with all-cause mortality (HR 24.5 [95% CI 7.9 to 76.0], p < 0.0001), which also counted for ST-T segment changes alone (HR 4.4 [95% CI 1.4 to 14.5], p = 0.02). After controlling for other risk factors, the HRs were 10.4 (95% CI 2.5 to 43.6, p = 0.001) for the combination and 2.7 (95% CI 0.6 to 12.3) for ST-T segment changes alone. CONCLUSIONS This study suggests that, in subjects with ST-T segment changes on their rest ECG, microalbuminuria could identify those at increased risk of all-cause and cardiovascular mortality.

Laboratory diagnosis of paraneoplastic pemphigus

Paraneoplastic pemphigus (PNP) is a multiorgan disease characterized by antibodies against plakins, desmogleins and the α2‐macroglobulin‐like‐1 (A2ML1) protein, in association with an underlying neoplasm. Accurate diagnosis relies on the demonstration of these autoantibodies in serum.