[Urinary tract infection caused by Candida while using an SGLT-2 inhibitor]. / Urineweginfectie door Candida bij gebruik SGLT2-remmer.

BACKGROUND: Sodium glucose transporter 2 (SGLT-2) inhibitors are a relatively new group of antidiabetic drugs. The renal glucose reabsorption is blocked resulting in higher glucose levels in the urine (glucosuria). Recently studies are being conducted into the medications nephrological and cardiovascular potential. As a result, we may expect that SGLT-2 inhibitors will be more and more frequently prescribed. Thus, physicians of any specialty may come into contact with patients that are using this drug. CASE DESCRIPTION: We describe a case of a male patient who developed a urinary tract infection with Candida glabrata while using a SGLT-2 inhibitor. After discontinuing the SGLT-2 inhibitor, the infection subsided. CONCLUSION: Urinary tract infections from Candida are rarely seen in healthy individuals. Glucosuria is a known risk factor for fungal genital infections. More research is needed to determine whether SGLT-2 inhibitors increase the risk of fungal urinary tract infections.

SCORE2 cardiovascular risk prediction models in an ethnic and socioeconomic diverse population in the Netherlands: an external validation study.

Background: Socioeconomic status and ethnicity are not explicitly incorporated as risk factors in the four SCORE2 cardiovascular disease (CVD) risk models developed for country-wide implementation across Europe (low, moderate, high and very-high model). The aim of this study was to evaluate the performance of the four SCORE2 CVD risk prediction models in an ethnic and socioeconomic diverse population in the Netherlands. Methods: The SCORE2 CVD risk models were externally validated in socioeconomic and ethnic (by country of origin) subgroups, from a population-based cohort in the Netherlands, with GP, hospital and registry data. In total 155,000 individuals, between 40 and 70 years old in the study period from 2007 to 2020 and without previous CVD or diabetes were included. Variables (age, sex, smoking status, blood pressure, cholesterol) and outcome first CVD event (stroke, myocardial infarction, CVD death) were consistent with SCORE2. Findings: 6966 CVD events were observed, versus 5495 events predicted by the CVD low-risk model (intended for use in the Netherlands). Relative underprediction was similar in men and women (observed/predicted (OE-ratio), 1.3 and 1.2 in men and women, respectively). Underprediction was larger in low socioeconomic subgroups of the overall study population (OE-ratio 1.5 and 1.6 in men and women, respectively), and comparable in Dutch and the combined "other ethnicities" low socioeconomic subgroups. Underprediction in the Surinamese subgroup was largest (OE-ratio 1.9, in men and women), particularly in the low socioeconomic Surinamese subgroups (OE-ratio 2.5 and 2.1 in men and women). In the subgroups with underprediction in the low-risk model, the intermediate or high-risk SCORE2 models showed improved OE-ratios. Discrimination showed moderate performance in all subgroups and the four SCORE2 models, with C-statistics between 0.65 and 0.72, similar to the SCORE2 model development study. Interpretation: The SCORE 2 CVD risk model for low-risk countries (as the Netherlands are) was found to underpredict CVD risk, particularly in low socioeconomic and Surinamese ethnic subgroups. Including socioeconomic status and ethnicity as predictors in CVD risk models and implementing CVD risk adjustment within countries is desirable for adequate CVD risk prediction and counselling. Funding: Leiden University Medical Centre and Leiden University.

Large health disparities in cardiovascular death in men and women, by ethnicity and socioeconomic status in an urban based population cohort.

BACKGROUND: Socioeconomic status and ethnicity are not incorporated as predictors in country-level cardiovascular risk charts on mainland Europe. The aim of this study was to quantify the sex-specific cardiovascular death rates stratified by ethnicity and socioeconomic factors in an urban population in a universal healthcare system. METHODS: Age-standardized death rates (ASDR) were estimated in a dynamic population, aged 45-75 in the city of The Hague, the Netherlands, over the period 2007-2018, using data of Statistics Netherlands. Results were stratified by sex, ethnicity (country of birth) and socioeconomic status (prosperity) and compared with a European cut-off for high-risk countries (ASDR men 225/100,000 and women 175/100,000). FINDINGS: In total, 3073 CVD deaths occurred during 1·76 million person years follow-up. Estimated ASDRs (selected countries of birth) ranged from 126 (95%CI 89-174) in Moroccan men to 379 (95%CI 272-518) in Antillean men, and from 86 (95%CI 50-138) in Moroccan women to 170 (95%CI 142-202) in Surinamese women. ASDRs in the highest and lowest prosperity quintiles were 94 (95%CI 90-98) and 343 (95%CI 334-351) for men, and 43 (95%CI 41-46) and 140 (95%CI 135-145), for women, respectively. INTERPRETATION: In a diverse urban population, large health disparities in cardiovascular ASDRs exists across ethnic and socioeconomic subgroups. Identifying these high-risk subgroups followed by targeted preventive efforts, might provide a basis for improving cardiovascular health equity within communities. Instead of classifying countries as high-risk or low-risk, a shift towards focusing on these subgroups within countries might be needed. FUNDING: Leiden University Medical Center and Leiden University.

[A woman with skin lesions and brain infarcts]. / Een vrouw met huidafwijkingen en herseninfarcten.

We present the case of a 58-year-old woman with multiple brain infarcts and livedo racemosa, a distinctive branched and irregular skin discoloration, on the trunk and limbs. Skin biopsy showed intimal proliferation with occlusion of a subcutaneous arteriole. We diagnosed Sneddon's syndrome, a rare neurocutaneous disorder likely caused by a noninflammatoryvasculopathy.

The impact of metabolic syndrome and CRP on vascular phenotype in type 2 diabetes mellitus.

BACKGROUND: The burden of cardiovascular disease in diabetes mellitus type 2 (DM2) patients is variable. We hypothesize that metabolic syndrome (MS) and low-grade systemic inflammation modify the extent of atherosclerosis in DM2. METHODS: Vascular phenotype was determined using the following endothelium-related, hemostatic, and sonographic endpoints in 62 DM2 patients with mild dyslipidemia: sVCAM, sE-selectin, von Willebrand factor (VWF), fibrinogen, s-thrombomodulin (sTM), tPA, PAI-1, flow-mediated dilation (FMD), and intima media thickness (IMT). The impact of MS load (number of criteria present), MS components, and CRP on these parameters was assessed. RESULTS: Serum sVCAM, sTM, and tPA levels significantly increased with increasing MS load. IMT also significantly increased from 0.602+/-0.034 (one MS criterion) to 0.843+/-0.145 (four MS criteria, p=0.007). LogCRP significantly correlated with fibrinogen, PAI-1, and IMT. In a multiple regression (MR) model with age and gender as covariates, MS load predicted sVCAM and sTM; CRP predicted PAI-1 and fibrinogen; MS load and CRP simultaneously predicted tPA and IMT. For each MS criterion present, IMT significantly increased by 0.04 mm. An increase in CRP from 1 to 3 mg/L resulted in a significant increase of 0.04 mm. Patients with four MS criteria and inflammation (CRP >or=3 mg/L) are predicted to have a 0.21 mm thicker IMT than those without. A second stepwise MR analysis based on gender, traditional risk factors, diabetes-related parameters, renal function, individual MS criteria, and LogCRP as explanatory variables showed a significant effect of systolic and diastolic blood pressure, HDL, and LogCRP on IMT(r(2)=0.36, p<0.001). CONCLUSION: MS and low-grade chronic inflammation have an independent impact on vascular phenotype including IMT in DM2.

The effect of statin therapy on endothelial function in type 2 diabetes without manifest cardiovascular disease.

OBJECTIVE: Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction. Flow-mediated dilation (FMD) is a noninvasive technique for measuring endothelial dysfunction. We aimed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD. RESEARCH DESIGN AND METHODS: A randomized, placebo-controlled, double-blind trial was performed with 250 type 2 diabetic patients. Patients were given 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, the 0.4 mg cerivastatin was replaced by 20 mg simvastatin, without deblinding the study. The primary end point was the change in FMD, measured by B-mode ultrasound, after 2 years. RESULTS: Determinants of baseline FMD were diabetes duration, common carotid intima-media thickness, and brachial artery diameter. FMD at baseline was 1.51% in the placebo group and 1.66% in the statin group and did not change significantly after 2 years. CONCLUSIONS: The 2-year statin therapy had no effect on FMD in type 2 diabetes. Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability.

No effect of statin therapy on silent myocardial ischemia in patients with type 2 diabetes without manifest cardiovascular disease.

OBJECTIVE: Coronary artery disease is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the prevalence of silent myocardial ischemia (SMI) and the effect of statin therapy on SMI in type 2 diabetic patients without manifest cardiovascular disease. RESEARCH DESIGN AND METHODS: A randomized, placebo-controlled, double-blind trial was performed in 250 patients with type 2 diabetes without manifest cardiovascular disease. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, cerivastatin 0.4 mg was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change in ischemic episodes, duration, and burden as measured by 48-h ambulatory electrocardiography (AECG) over 2 years. RESULTS: At baseline, 47 of 233 (20%) evaluable ambulatory electrocardiograms showed evidence of ischemia. After 2 years, there was a trend toward more ischemia in both treatment groups, without significant differences between the changes in ischemic parameters (episodes P = 0.498; duration P = 0.697; burden P = 0.798) in the two treatment groups. Cardiovascular events occurred in 12 patients in the placebo group and in two patients in the statin group (P = 0.006). There was no relationship between these cardiovascular events and the presence of SMI at baseline. CONCLUSIONS: SMI occurred in 20% of type 2 diabetes patients without manifest cardiovascular disease. There was no effect from 2 years of statin therapy on SMI. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. AECG may not be a proper tool for risk stratification in patients with type 2 diabetes.

Pharmacological strategies to reduce cardiovascular risk in type 2 diabetes mellitus: an update.

Morbidity and mortality in patients with type 2 diabetes mellitus is largely dominated by the occurrence of cardiovascular disease (CVD). Treatment of known risk factors of CVD has proven to be beneficial in terms of reduction in risk of major CVD events in the general population. Recent trials have provided information on the treatment of hyperglycaemia, hypertension, dyslipidaemia and platelet aggregation in the patient with type 2 diabetes. Strict glycaemic control is not associated with a significant reduction in CVD risk, although new hypoglycaemic agents may offer additional benefits. In contrast, it has been demonstrated that treatment of hypertension and dyslipidaemia significantly reduce cardiovascular risk. Meticulous control of blood pressure to a level < or =130/80 mm Hg, preferably using renin-angiotensin system-modulating agents, is of proven value. Use of HMG-CoA reductase inhibitors (statins) as low-density lipoprotein (LDL)-cholesterol-lowering therapy, initiated at a level of > or =2.60 mmol/L is firmly established. Recent trials lend support to lowering the target level for LDL-cholesterol-lowering therapy to < or =1.81 mmol/L. Mainly based on risk analogy, international guidelines advocate the use of aspirin (acetylsalicylic acid) in the primary prevention of CVD in patients with type 2 diabetes. However, there is no support from large trials that the estimated 25% risk reduction in primary prevention in a high-risk population is the same in the subgroup with diabetes. An intensified approach in order to identify and treat cardiovascular risk factors in patients with type 2 diabetes, stratified to individual patients, is necessary to reduce the excess cardiovascular burden of these patients.

Two-year statin therapy does not alter the progression of intima-media thickness in patients with type 2 diabetes without manifest cardiovascular disease.

OBJECTIVE: Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness (IMT) in type 2 diabetic patients without manifest CVD. RESEARCH DESIGN AND METHODS: A randomized, placebo-controlled, double-blind clinical trial was performed in 250 patients with type 2 diabetes. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change of mean common carotid IMT, as measured by B-mode ultrasound, over 2 years. RESULTS: Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years. There was no significant difference in IMT change in any carotid segment between the groups. LDL cholesterol was reduced by 25% in the statin group and increased by 8% in the placebo group (P <0.001). Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group (P=0.006). CONCLUSIONS: There was no effect of 2 years' statin therapy on carotid IMT in type 2 diabetic subjects. The natural history of IMT in our patients was milder than anticipated. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. Prognostic tools other than IMT should be explored in this patient group.