Identification of predictive factors of diabetic ketoacidosis in type 1 diabetes using a subgroup discovery algorithm.

AIM: To identify predictive factors for diabetic ketoacidosis (DKA) by retrospective analysis of registry data and the use of a subgroup discovery algorithm. MATERIALS AND METHODS: Data from adults and children with type 1 diabetes and more than two diabetes-related visits were analysed from the Diabetes Prospective Follow-up Registry. Q-Finder, a supervised non-parametric proprietary subgroup discovery algorithm, was used to identify subgroups with clinical characteristics associated with increased DKA risk. DKA was defined as pH less than 7.3 during a hospitalization event. RESULTS: Data for 108 223 adults and children, of whom 5609 (5.2%) had DKA, were studied. Q-Finder analysis identified 11 profiles associated with an increased risk of DKA: low body mass index standard deviation score; DKA at diagnosis; age 6-10 years; age 11-15 years; an HbA1c of 8.87% or higher (≥ 73 mmol/mol); no fast-acting insulin intake; age younger than 15 years and not using a continuous glucose monitoring system; physician diagnosis of nephrotic kidney disease; severe hypoglycaemia; hypoglycaemic coma; and autoimmune thyroiditis. Risk of DKA increased with the number of risk profiles matching patients' characteristics. CONCLUSIONS: Q-Finder confirmed common risk profiles identified by conventional statistical methods and allowed the generation of new profiles that may help predict patients with type 1 diabetes who are at a greater risk of experiencing DKA.

Hypercholesterolemia diagnosis, treatment patterns and target achievement in patients with acute coronary syndromes in Germany.

BACKGROUND: Patients who experience an acute coronary syndrome (ACS) are at high risk of further cardiovascular events. Long-term treatment of cardiovascular risk factors, such as hyperlipidemia, is critical to prevent progression of coronary heart disease. However, many patients do not reach recommended target levels for low-density lipoprotein (LDL) cholesterol, despite receiving lipid-lowering therapy. OBJECTIVE: To obtain an insight into the current treatment situation for very high-risk patients after an initial ACS in Germany. METHODS: The multicenter HYDRA-ACS registry study was initiated to document the clinical characteristics of very high-risk patients with ACS and hyperlipidemia in clinical practice. In addition, lipid profiles, lipid-lowering therapy, and lipid target achievement during treatment were documented over 1 year. RESULTS: 353 patients who were documented had a mean age of 57.3 years, mean body mass index was 28.6 kg/m2, and 73.4% were male; 52.4% had a family history of myocardial infarction (MI) and 32.6% a family history of coronary heart disease (CHD). Patients' medical histories commonly included CHD (32.9%), percutaneous coronary intervention (PCI; 25.5%), and previous ACS (23.0%). Common comorbidities included hypertension (68.6%), diabetes (17.3%), heart failure (16.7%), and stable angina pectoris (15.9%). The proportion of patients receiving lipid-lowering therapy increased from 65.7% at baseline to 100% at the 12-month follow-up (p < 0.0001). Substantial increases in use were seen for statins (85.0% vs. 36.5%, p = 0.0002) and cholesterol resorption inhibitors (32.9% vs. 8.6%, p = 0.0003). Use of combination therapy increased. The proportion of patients undertaking physical exercise increased (p < 0.0001), as did consumption of fruit and vegetables (p = 0.0222) and fish (p = 0.0162), while alcohol consumption decreased (p = 0.0019). Median LDL cholesterol level decreased significantly from baseline (87 vs. 166 mg/dL, p < 0.0001), and the proportion of patients with a level < 70 mg/dL increased (50.0% vs. 5.7%, p < 0.0001). Median HDL cholesterol increased (47 vs. 45 mg/dL, p = 0.0235) and median triglyceride level decreased (119 vs. 148 mg/dL, p = 0.0080). The proportion of patients receiving antihypertensive drugs and platelet aggregation inhibitors increased. The most frequent cardiovascular events during the 12-month follow-up were PCI (25.9%) and cardiac catheterization without PCI (12.9%); MI occurred in 2.4% of patients; no deaths were reported. CONCLUSIONS: This study provides a contemporary picture of the treatment of hyperlipidemia after ACS in patients in Germany. Despite treatment with lipid-lowering therapy, many patients did not achieve recommended lipid targets by 12 months after an ACS event.

Hypercholesterolemia Diagnosis, Treatment Patterns, and 12-Month Target Achievement in Clinical Practice in Germany in Patients with Familial Hypercholesterolemia.

Background: Familial hypercholesterolemia (FH) is a highly prevalent disorder and a risk factor for early coronary artery disease. The objective of this registry was to document the clinical characteristics of patients with definite FH in Germany and to document lipid profiles, lipid-lowering therapy, and lipid target achievement during longitudinal follow-up. Methods: HYDRA-FH was a national, prospective, multicenter, non-interventional registry conducted in 35 centers in Germany. Consecutive adult patients with definite FH were included (n = 241). Results: In the cross-sectional analysis (n = 233), lipid-lowering therapy involved statins (82.0%), ezetimibe (31.8%), and PCSK9 antibodies (18.5%); 11.2% of patients were receiving no lipid-lowering drugs. Median lipid levels were: low-density lipoprotein cholesterol (LDL-C) 134 mg/dL (3.5 mmol/L), high-density lipoprotein cholesterol (HDL-C) 48 mg/dL (1.2 mmol/L), triglycerides 160 mg/dL (1.9 mmol/L), total cholesterol 211 mg/dL (5.5 mmol/L). Values were above the normal threshold (150 mg/dL) for LDL-C in 72.9%, total cholesterol in 29.7%, and triglycerides in 45.0% of patients. After the 12-month follow-up (n = 145), only 17.2% had LDL-C < 70 mg/dL, and 20.7% had either LDL-C < 70 mg/dL or a reduction of ≥50% versus baseline. Conclusion: This study provides insight into the clinical characteristics and current treatment status of patients with FH in Germany. Many patients with FH do not achieve recommended lipid levels.

Intensified lipid-lowering treatment with alirocumab in patients with coronary heart disease.

BACKGROUND: Atherosclerotic cardiovascular disease is the leading cause of death and disability in the Western world. OBJECTIVE: To characterise adults with confirmed coronary heart disease (CHD) and primary heterozygous familial or non-familial hypercholesterolaemia or mixed dyslipidaemia who received alirocumab in a real-world setting. METHODS: This open, prospective, multicentre, non-interventional study, conducted in Germany, enroled patients with confirmed CHD who were treated with alirocumab according to its summary of product characteristics. Prescription was at the physician's discretion and independent of study participation. Patients were followed for 12 weeks after alirocumab initiation. RESULTS: In total, 245 patients (mean age 62.2 years; 34.0% female) were documented at 90 sites. Overall, 47.7% had familial hypercholesterolaemia, 48.9% non-familial hypercholesterolaemia and 43.8% mixed dyslipidaemia; 74.6% had hypertension and 29.2% diabetes mellitus. The most common lipid-lowering therapy in the 12 months preceding alirocumab was a statin, often in combination with ezetimibe (73.5%). Statin contraindications were documented for 46.2% patients and statin intolerance for 63.8%. The mean low-density lipoprotein cholesterol (LDL-C)-level prior to alirocumab was 150.5±51.6 mg/dL. Alirocumab prescription was in compliance with German national recommendations and/or European guidelines. The most common starting dose was 75 mg every other week. Overall, 57% patients reached target LDL-C levels (<70 mg/dL) after 12 weeks of treatment. Alirocumab was generally well tolerated. CONCLUSION: In a real-world setting in Germany, alirocumab was prescribed for patients with atherosclerotic cardiovascular disease who had high baseline LDL-C levels with or without statin intolerance. Efficacy and safety were consistent with findings observed in the ODYSSEY Phase III programme.

PEARL: A Non-interventional Study of Real-World Alirocumab Use in German Clinical Practice.

BACKGROUND: Several lipid guidelines recommend that proprotein convertase subtilisin/kexin type 9 inhibitors should be considered for patients with atherosclerotic cardiovascular disease who are inadequately treated with maximally tolerated lipid-lowering treatment. OBJECTIVES: The PEARL study assessed the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in patients with hypercholesterolemia in a real-world setting. METHODS: PEARL was an open, prospective, multicenter, non-interventional study conducted in Germany. Patients (n = 619) for whom treating physicians decided to use alirocumab 75 or 150 mg every 2 weeks according to German guidelines (low-density lipoprotein cholesterol > 1.8/2.6 mmol/L [> 70/100 mg/dL], depending on cardiovascular risk, despite maximally tolerated statin therapy with/without other non-alirocumab lipid-lowering therapy) were enrolled and followed for 24 weeks. Physicians could adjust the alirocumab dose based on their clinical judgment. The primary efficacy endpoint was low-density lipoprotein cholesterol reduction from baseline (prior to alirocumab therapy) to week 24. RESULTS: Overall, 72.8% of patients reported complete or partial statin intolerance. Mean low-density lipoprotein cholesterol was 4.7 mmol/L (180.5 mg/dL) and 2.3 mmol/L (89.8 mg/dL) at baseline and week 24, respectively. Least-squares mean percentage change from baseline to week 24 in low-density lipoprotein cholesterol was - 48.6%. Initial alirocumab dose was 75 mg in 72.9% of patients and 150 mg in 24.5% of patients; 19.6% of patients received an alirocumab dose increase (75 to 150 mg) and 1.6% of patients received a dose decrease. Adverse events were reported in 10.3% of patients, with myalgia being the most common. CONCLUSIONS: In a real-world setting in Germany, alirocumab was used in patients who had high baseline low-density lipoprotein cholesterol levels with/without statin intolerance. Efficacy and safety were consistent with findings observed in the ODYSSEY Phase III program.

[Adaptive drug licensing: A chance for patients?]. / Frühere Zulassung von Arzneimitteln - Eine Chance für Patienten?

In recent years, various options have been discussed to accelerate the approval of new drugs, especially for conditions with high unmet needs. There is a trade-off between the earlier availability of new treatment options and a potentially higher safety risk of drugs which have not been investigated in long-lasting clinical trials and a broader patient population. It must also be taken into account that clinical trial data and results must be sufficient to allow for the reimbursement of the new treatment option. The difficult process of weighting the benefits against the potential risks of an accelerated drug approval should be discussed between patients, regulatory authorities, HTA institutions and pharmaceutical companies. Patients might benefit from a fair, balanced accelerated approval.

Benefits and risks of preventing thromboembolism with enoxaparin in patients with general surgery in real world--the CLEVER study.

BACKGROUND: We aimed to document enoxaparin use in real world and identify the risk factors for bleeding complications. METHODS: Postauthorization study in 448 surgical patients receiving enoxaparin prophylaxis. Complete compression ultrasound (CCUS) was performed at day 10 ± 3. RESULTS: During treatment, 11 of 448 patients had suspected deep venous thrombosis (DVT) but none confirmed. One patient had symptoms of pulmonary embolism ([PE] 0.22%; 95% confidence interval [CI] -0.21-0.66). There were no asymptomatic cases detected upon CCUS. At the 90-day follow-up, 4 (0.9%) of the 440 patients had DVT symptoms (95% CI 0.02-1.80) and none had PE; 5.4% had major and 11.6% any type of bleeding complications. Major bleeding was more frequent in those with kidney disease (odds ratio [OR] 5.53), those who are bedridden (OR 5.49), those with peridural indwelling catheters (OR 4.01), and those on nonsteroidal anti-inflammatory drugs (OR 3.33). CONCLUSIONS: Enoxaparin is effective and safe in surgical patients to prevent venous thromboembolism.

Ramipril-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes (ADaPT) study.

BACKGROUND: Previous randomized controlled trials demonstrated a protective effect of renin angiotensin system blocking agents for the development of type-2 diabetes in patients with pre-diabetes. However, there are no real-world data available to illustrate the relevance for clinical practice. METHODS: Open, prospective, parallel group study comparing patients with an ACE inhibitor versus a diuretic based treatment. The principal aim was to document the first manifestation of type-2 diabetes in either group. RESULTS: A total of 2,011 patients were enrolled (mean age 69.1±10.3 years; 51.6% female). 1,507 patients were available for the per-protocol analysis (1,029 ramipril, 478 diuretic group). New-onset diabetes was less frequent in the ramipril than in the diuretic group over 4 years. Differences were statistically different at a median duration of 3 years (24.4% vs 29.5%; p<0.05). Both treatments were equally effective in reducing BP (14.7±18.0/8.5±8.2 mmHg and 12.7±18.1/7.0±8.3 mmHg) at the 4 year follow-up (p<0.001 vs. baseline; p=n.s. between groups). In 38.6% and 39.7% of patients BP was below 130/80 mmHg (median time-to-target 3 months). There was a significant reduction of cardiovascular morbidity and mortality in favour of ramipril (p=0.033). No significant differences were found for a change in HbA1c as well as for fasting blood glucose levels during follow-up. The rate of adverse events was higher in diuretic treated patients (SAE 15.4 vs. 12.4%; p<0.05; AE 26.6 vs. 25.6%; p=n.s). CONCLUSIONS: Ramipril treatment is preferable over diuretic based treatment regimens for the treatment of hypertension in pre-diabetic patients, because new-onset diabetes is delayed.

Blood pressure management in a cohort of hypertensive patients in Germany treated by cardiologists.

BACKGROUND: In Germany, an estimated 20-25 million patients suffer from hypertension. Blood pressure control rates are, however, lower than in many other European countries and the USA. The present analysis reports blood pressure treatment and control rates in Germany in patients with hypertension treated by cardiologists. METHODS: The present analysis reports data from a German subgroup analysis of a large, multinational, observational survey i-SEARCH that recruited patients in 2005/2006. It reports blood pressure readings, drug utilization and control rates in cardiology practice. RESULTS: A total of 4,982 patients were documented at 417 sites. Mean systolic/diastolic blood pressure (SBP/DBP) was 152 ± 19.5/88.4 ± 11.5 mmHg. SBP was 1.3 mmHg higher in men than in women (p = 0.021). The majority of patients had an SBP between 141 and 160 mmHg and 31.4% of patients had normal SBP. Overall blood pressure control rate was only 11.6% [95% CI 10.7-12.6] in treated patients. It was different in men [10.2%; 95% CI 9.0-11.6] than in women [8.1%; 95% CI 7.1-9.4; p = 0.008] and higher in patients without diabetes [12.7%; 95% CI 11.6-14.0] than in those with diabetes [4.3%; 95% CI 3.4-5.4; p < 0.0001]. One-third of patients received either monotherapy or dual therapy, or three and more drugs, respectively; 42.2% of patients received guideline-recommended dual combination therapy. A combination of beta-blockers + ACE inhibitors was most frequently prescribed (30.8%). CONCLUSIONS: Our data indicate a low level of blood pressure control, especially in patients at an increased risk for cardiovascular events, such as those with diabetes or cardiovascular comorbidities. Major efforts are required to improve hypertension management as recommend by current treatment guidelines.

Follow-up of cardiovascular risk markers in hypertensive patients treated with irbesartan: results of the i-SEARCH Plus Registry.

Microalbuminuria (MAU), high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) are risk markers used to predict the prognosis of hypertensive patients; however, they have not been prospectively evaluated in primary care. An investigation was conducted using i-SEARCH Plus, a registry documenting 1649 patients with hypertension who received irbesartan at office-based cardiologists over 12 months. Mean age at baseline was 61.4±11.3 years, 43.2% were women, and blood pressure was 159.8±20.1/93.4±11.9mm Hg. Median albumin/creatinine ratio (ACR) at baseline was 9.90 (interquartile range [IQR], 5.76--25.52) mg/g, hsCRP 2.46 (IQR, 1.16--5.14) mg/L, and NT-proBNP 89.28 (IQR, 38.63-203.40) pg/mL. In patients with MAU (ACR ≥20mg/g), the age-adjusted risk of a combined end point of newly diagnosed coronary artery disease (CAD), myocardial infarction, stroke/transitory ischemic attack, and death at 12-month follow-up was increased (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.49-4.76), as was the incidence of CAD (OR, 3.27; 95%CI, 1.39-7.68) and death (OR, 4.63; 95%CI, 1.44-14.94). No correlations with end points were found for hsCRP or NT-proBNP after adjusting for age and the presence of MAU. MAU is an independent predictor of cardiovascular events in hypertensive patients. These findings confirm previous reports on the prognostic value of MAU and establish its incremental value over hsCRP and NT-proBNP.

Prevalence of microalbuminuria and its associated cardiovascular risk: German and Swiss results of the recent global i-SEARCH survey.

QUESTION UNDER STUDY: The aim of this study was to determine the prevalence of microalbuminuria (MAU) in hypertensive patients attending an office or hospital based cardiologist or internist. An additional aim was to describe associations between MAU and cardiovascular risk factors as well as to investigate the role of pharmacotherapy. METHODS: International, observational, cross-sectional study of 22282 patients with 5605 attendees in Germany and Switzerland at 444 cardiology centers. Inclusion criteria were male and female outpatients, aged > or =18 years with currently treated or newly diagnosed hypertension (> or =140/90 mm Hg at rest on the day of the study visit) and no reasons for false positive dip stick tests. The main outcome measures were the prevalence of MAU, co-morbid cardiovascular risk factors or disease and their association with the presence of MAU, and the role of pharmacotherapy in modulating prevalence of MAU. RESULTS: Prevalence of MAU in Germany and Switzerland (53.1%) was high, but lower when compared to the prevalence in "other countries" (OC, 60.2%). Routine MAU measurement was performed in 52.9% of the practices only (32.9% OC), although physicians regarded MAU to be important for risk assessment and therapeutic decisions. MAU is highly correlated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions including high waist circumference (55.1% [95%CI 56.0; 59.7]), diabetes (59.1% [56.8; 61.3]), atrial fibrillation (62.3% [57.4; 66.9]) and peripheral arterial disease (67.1% [61.6; 72.2]). Angiotensin receptor blockers (ARBs) appeared to be associated with the lowest risk of MAU (52.1%). Calcium channel blockers (CCBs) were used more frequent in patients with MAU (28.7%) than without (23.4%). CONCLUSIONS: Patients with MAU are common in clinical cardiology and its presence is associated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions. A more aggressive multi-factorial treatment might help to reduce this risk constellation.

First-line antihypertensive treatment in patients with pre-diabetes: rationale, design and baseline results of the ADaPT investigation.

BACKGROUND: Recent clinical trials reported conflicting results on the reduction of new-onset diabetes using RAS blocking agents. Therefore the role of these agents in preventing diabetes is still not well defined. Ramipril is an ACE inhibitor (ACEi), that has been shown to reduce cardiovascular events in high risk patients and post-hoc analyses of the HOPE trial have provided evidence for its beneficial action in the prevention of diabetes. METHODS: The ADaPT investigation ("ACE inhibitor-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes") is a 4-year open, prospective, parallel group phase IV study. It compares an antihypertensive treatment regimen based on ramipril versus a treatment based on diuretics or betablockers. The primary evaluation criterion is the first manifestation of type 2 diabetes. The study is conducted in primary care to allow the broadest possible application of its results. The present article provides an outline of the rationale, the design and baseline characteristics of AdaPT and compares these to previous studies including ASCOT-BLPA, VALUE and DREAM. RESULTS: Until March 2006 a total of 2,015 patients in 150 general practices (general physicians and internists) throughout Germany were enrolled. The average age of patients enrolled was 67.1 +/- 10.3 years, with 47% being male and a BMI of 29.9 +/- 5.0 kg/m2. Dyslipidemia was present in 56.5%. 37.8% reported a family history of diabetes, 57.8% were previously diagnosed with hypertension (usually long standing). The HbA1c value at baseline was 5.6 %. Compared to the DREAM study patients were older, had more frequently hypertension and patients with cardiovascular disease were not excluded. CONCLUSION: Comparing the ADaPT design and baseline data to previous randomized controlled trial it can be acknowledged that AdaPT included patients with a high risk for diabetes development. Results are expected to be available in 2010. Data will be highly valuable for clinical practice due to the observational study design.

[Perioperative Bridging with Enoxaparin. Results of the Prospective BRAVE Registry with 779 Patients]. / Perioperative überbrückende Antikoagulation mit Enoxaparin. Ergebnisse des prospektiven BRAVE-Registers mit 779 Patienten.

BACKGROUND AND PURPOSE: Oral anticoagulant (OAC) therapy should be temporarily interrupted for an elective procedure or surgery, and perioperative prophylaxis with heparins should be initiated in patients who face a high or moderate risk of thrombosis. To date, the optimal heparin dose has not been established. The authors investigated the efficacy and safety of a risk-adapted regimen with the low-molecular-weight heparin enoxaparin in two different, body weight-adapted regimens. PATIENTS AND METHODS: In the own institution, adult patients were consecutively documented in the prospective BRAVE registry, if they required bridging therapy. Patients with moderate thromboembolic risk (35.7%) received, after interruption of OAC and reaching an International Normalized Ratio (INR) of 1.5, enoxaparin 1 mg/kg body weight daily, those with high risk (64.3%) enoxaparin 1 mg/kg body weight twice daily (in case of compromised renal function half this dose, respectively). Events were recorded at 30 days post intervention by on-site examination of the patient or telephone follow-up. RESULTS: Of 779 patients, none had a thromboembolic event. Enoxaparin was well tolerated. A total of four major bleedings in three patients (0.5%, all in the high-risk group), 46 minor bleedings (5.9%), and twelve cases of thrombocytopenia (1.5%, however, no heparin-induced thrombocytopenia [HIT] II) were noted. CONCLUSION: The absence of thromboembolic events confirms the efficacy of enoxaparin in perioperative bridging. The rate of major bleedings was low and, of note, no cases of HIT II were noted. Reducing the dose to half the standard was shown to be effective and well tolerated in patients with moderate risk. Likewise, enoxaparin in a reduced dose can be safely used in patients with renal insufficiency who require bridging.

[Long-term follow-up of cardiovascular risk markers in patients with hypertension. Rationale, design, and baseline characteristics of the i-Search Plus Registry]. / Langzeitverlauf kardiovaskulärer Risikomarker bei Patienten mit Hypertonie. Rationale, Design und Ausgangscharakteristika des i-SEARCH Plus Registers.

BACKGROUND: Cardiovascular risk markers like microalbuminuria (MAU), highly sensitive C-reactive protein (hsCRP) and brain natriuretic peptide (BNP) currently gain importance to estimate risk in trials and clinical practice. Blockade of the renin-angiotensin system (RAS) has been shown to reduce some of these risk markers in clinical trials, but validation of their time course and role in clinical practice is still pending. DESIGN: To fill this gap, the design of a nationwide registry study was chosen in which patients attending their cardiologist were observed for 12 months and the effect of blocking the RAS with the angiotensin II receptor blocker irbesartan was documented. Primary question: risk for mortality and the incidence of cardiovascular events in relation to baseline values of MAU, hsCRP, and BNP. Secondary questions: correlations between cardiovascular risk markers (1) amongst each other with respect to cardiovascular events, (2) with clinical findings (echocardiography, electrocardiogram), (3) with the heart rate, (4) with further metabolic parameters (blood sugar, HbA(1c), etc.), and (5) with blood pressure control. RESULTS: Until April 1, 2006, 2,149 patients were recruited in 305 centers in Germany. Patients had a mean age of 61.4 (+/- 11.3) years. Waist circumference was 103.6 (+/- 13.5) cm. 95.1% of all patients had arterial hypertension at inclusion (> or = 140/90 mmHg). The mean value for albumin/creatinine was 68.9 (+/- 307.5) mg/g (n = 2,100), for hsCRP 4.6 (+/- 8.3) mg/l (n = 2,136), and for proBNP 236.5 (+/- 557.3) pg/ml (n = 2,138). CONCLUSION: The present register will elucidate the time course and the interdependence of the cardiovascular risk markers MAU, hsCRP and proBNP as well as their prediction of cardiovascular endpoints in hypertensive individuals. In addition, the role of RAS-blocking agents will be evaluated. A valuable contribution to estimate risk and to optimize care for cardiovascular high-risk patients in clinical practice can be expected.

[Albuminuria: an indicator of cardiovascular risk]. / Albuminurie: ein kardiovaskulärer Risikoindikator.

BACKGROUND: The transition of albumin from the vascular lumen into the surrounding tissue always indicates a serious disturbance of the vascular wall. Clinically, this process can be recognized as "cotton-wool" spots of the retina or by testing the urine for the presence of albumin. The appearance of albumin in the urine is pathologic and should be evaluated within the context of the accompanying cardiovascular risk. PATHOPHYSIOLOGY AND DEFINITIONS: Albumin transition is indicative of a disturbance of the barrier function of endothelial cells. In the kidney, damage to podocytes, mesangial and endothelial cells, a loss of charge selectivity, and an altered expression of matrix proteins can be observed. However, vascular alterations are not confined to the kidney but can also be observed in the myocardium. Even though thresholds for microalbuminuria (> 30 mg/24 h) and proteinuria (> 300 mg/24 h) have been arbitrarily defined, an increase in risk starts at much lower levels of albumin excretion. PREVALENCE AND PROGNOSTIC IMPORTANCE: The prevalence of microalbuminuria in the general population is about 8%. However, prevalence rates of > 50% have been observed in high-risk groups, which are accompanied by an increased risk for cardiovascular morbidity and mortality. THERAPEUTIC OPTIONS: A number of therapeutic options (tight blood sugar control, blood pressure reduction, lipid lowering) lead to a reduction of albuminuria and an improvement in cardiovascular prognosis. This has particularly been described for renin-angiotensin-aldosterone system-(RAAS-)blocking agents. Their use is not only associated with a reduced risk of end-organ damage (heart failure, diabetic nephropathy, cerebrovascular events) but has been described to decrease mortality as well. RECOMMENDATION: A timely diagnosis, a consecutive cardiovascular diagnostic work-up and the subsequent use of RAAS-blocking agents is indicated in patients in whom albuminuria has been diagnosed.

Prevalence of deep vein thrombosis (DVT) in non-surgical patients at hospital admission.

Venous thromboembolism (VTE) is known as a common complication in surgical and non-surgical patients. We hypothesized that according to the underlying risk factors and the acute illness, the prevalence ofVTE in non-surgical patients admitted to hospital is widely underestimated. For three months each patient admitted to the department of internal medicine with an acute illness, but without known deep venous thrombosis (DVT) was investigated by ultrasound compression sonography. Patients' history, risk factors and extent of immobilisation were documented. In patients with newly detected DVT D-dimer and fibrinogen were measured as well as computer tomography scans performed. Follow-up investigations of the DVT population were performed at four weeks and three months. Six hundred seventeen patients (49.3% men) were included. In 16 patients (men = 7) a previously unknown thrombosis (2.6%) was detected, mainly in patients with acute cardio-pulmonary disease (56%) and the elderly (mean age 75.6 years). Eight patients had femoro-popliteal (50.0%), four a femoral (25.0%), and four a popliteal vein thrombosis (25.0%). Five had pulmonary embolism (31.3%). In patients with DVT D-dimer was 875 +/- 1,228 mg/l, fibrinogen 568 +/- 215 mg/dl and C-reactive-protein 58.54 +/- 73.65 mg/dl. One patient died from sepsis during hospitalisation, one died from sudden cardiac death at home. None of the other 14 surviving patients relapsed. The study shows a 2.6% risk for DVT in outpatients with acute illness admitted to the department of internal medicine. These data demonstrate the high risk of DVT is in non-surgical patients. Early prophylaxis has to be considered in internal medicine patients especially in the elderly.

Low-grade albuminuria and cardiovascular risk : what is the evidence?

Microalbuminuria (MA), conventionally defined as a urinary albumin excretion (UAE) of 30-300 mg/day, is recognised as a marker of endothelial dysfunction. Furthermore, it represents an established risk factor for cardiovascular morbidity and mortality and for end-stage renal disease in individuals with an adverse cardiovascular risk profile. It is common in the general population, particularly in patients with diabetes mellitus or arterial hypertension. There is growing evidence from prospective observational trials that UAE levels well below the current MA threshold ("lowgrade MA") are also associated with an increased risk of incident cardiovascular disease and allcause mortality. Even in apparently healthy individuals (without diabetes or hypertension), such an association has been shown. As albuminuria screening assays that are reliable even in the lower ranges are commercially available, there may be an important clinical role for MA in disease screening, comparable to the role of blood pressure and lipid screening. MA is modifiable, and the inhibition of the renin-angiotensin system by ACE inhibitors and AT1 receptor antagonists has been shown to result in a lower incidence of cardiovascular events.

Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: a sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients.

OBJECTIVES: The metabolic syndrome is a cluster of cardiovascular risk factors leading to an increased risk for the subsequent development of diabetes and cardiovascular morbidity and mortality. Blocking the renin-angiotensin system has been shown to prevent cardiovascular disease and delay the onset of diabetes. Irbesartan is an angiotensin receptor blocker (ARB) which has been shown to possess peroxisome proliferator-activated receptor gamma (PPARgamma) activating properties, and to have a favorable metabolic profile. Current discussion is whether the addition of small doses of hydrochlorothiazide changes this profile. Therefore the efficacy, safety and metabolic profile of Irbesartan either as monotherapy or in combination therapy was assessed in patients with the metabolic syndrome in a large observational cohort in primary care. RESEARCH DESIGN AND METHODS: Multicenter, prospective, two-armed, post authorization study over 9 months in 14,200 patients with uncontrolled hypertension with and without the metabolic syndrome (doctors' diagnosis based on the Adult Treatment Panel III criteria 2001). Blood pressure was measured sphygmomanometrically and cardiovascular risk factors making up the criteria for the metabolic syndrome were assessed. MAIN OUTCOME MEASURES: Systolic (SBP) and diastolic (DBP) blood pressure reduction, response, and normalization (systolic and diastolic), changes in fasting glucose, waist circumference (abdominal obesity), serum triglycerides and HDL cholesterol as well as the proportion of patients fulfilling the criteria for the metabolic syndrome. Number and nature of adverse events (AEs). RESULTS: After 9 month the use of Irbesartan in monotherapy resulted in a significant reduction of blood pressure (SBP: -26.3 +/- 10.1 mmHg/DBP-13.0 +/- 6.6 mmHg, both p < 0.0001) in patients with the metabolic syndrome. This was accompanied by a reduction in cardiovascular risk factors: HDL cholesterol (+3.6 +/- 7.2 mg/dl in men, +3.8 +/- 6.5 mg/dl in women, both p < 0.0001), serum triglycerides (-28.6 +/- 52.1 mg/dl, p < 0.0001), fasting blood glucose (-8.4 +/- 25.1 mg/dl, p < 0.0001) and waist circumference (-2.4 +/- 11.9 cm in men, -1.2 +/- 14.2 in women, both p < 0.0001) were significantly improved. Irbesartan combination therapy (12.5 mg HCTZ) in patients with the metabolic syndrome: blood pressure reduction (SBP: -27.5 +/- 10.1 mmHg/DBP: -14.1 +/- 6.6 mmHg, both p < 0.0001), improvement in HDL cholesterol (+4.0 +/- 6.8 mg/dl in men, +3.4 +/- 6.8 in women, both p < 0.0001), triglycerides (-34.1 +/- 52.6 mg/dl, p < 0.0001), fasting blood glucose (-10.0 +/- 24.7, p < 0.0001) and waist circumference (-3.2 +/- 12.7 cm in men, -1.7 +/- 14.4 in women, both p < 0.0001). Tolerability was excellent: only 0.6% of patients experienced an AE. CONCLUSION: There was a significant improvement in blood pressure and metabolic risk factors as a result of Irbesartan treatment. There was no evidence of a difference between monotherapy and combination therapy with regard to the cardiovascular risk profile.

Quality of anticoagulation with unfractionated heparin plus phenprocoumon for the prevention of thromboembolic complications in cardioversion for non-valvular atrial fibrillation. Sub-analysis from the Anticoagulation in Cardioversion using Enoxaparin (ACE) trial.

INTRODUCTION: Anticoagulation in cardioversion for atrial fibrillation is performed using unfractionated heparin and oral anticoagulants. TEE-guided cardioversion, after achievement of therapeutic anticoagulation (1-3 days), may be an alternative to the traditional procedure (3-week anticoagulation followed by cardioversion). The quality of anticoagulation in atrial fibrillation has not been investigated in a randomised trial with TEE-guided cardioversion. We analysed respective data from the ACE trial on the quality of conventional anticoagulation, where most participating centres chose the TEE-guided approach. MATERIALS AND METHODS: In a randomised, prospective, multicentre trial, we analysed the efficacy of unfractionated heparin plus phenprocoumon in 248 patients on an intention-to-treat basis. There were 2373 evaluable anticoagulation measurements (out of 2925 measurements) and 4 categories of anticoagulation quality (under-, target, over- and severe over-anticoagulation). Of patients with evaluable measurements, 88% received short-term anticoagulation (4 weeks) in TEE-guided cardioversion. RESULTS: The median time to achieve therapeutic anticoagulation (aPTT> or =60 and <80 s or INR> or =2 and <3) was 3 days. Anticoagulation values were out of therapeutic range in 69.5% of measurements during 4- or 7-week follow-up, and never within therapeutic range in 10% of patients. Of the 15 primary endpoints observed (death, thromboembolism and major bleeding complications), only 3 were in patients with anticoagulation measurements within therapeutic range. CONCLUSIONS: In this study setting, with predominance of 4 weeks anticoagulation in TEE-guided cardioversion for atrial fibrillation, therapeutic anticoagulation was reached within 3 days using conventional anticoagulation. Despite careful dose adjustments, anticoagulation was out of therapeutic range in almost 70% of total measurements and 80% of primary endpoints.