Lipid profiles of patients with manifest coronary versus peripheral atherosclerosis - Is there a difference?

AIM: Peripheral arterial disease (PAD) and coronary artery disease (CAD) are both caused by atherosclerosis. Serum lipids and lipoproteins are predictive of the development of atherosclerosis but it is not clear if they differ in the two manifestations, PAD and CAD. We tested whether a more detailed characterization of the lipid and lipoprotein patterns of PAD and CAD allows a clear differentiation between the two atherosclerotic phenotypes. METHODS: A cohort of 274 statin-naïve patients with either newly diagnosed imaging proven PAD (n = 89) or stable CAD (n = 185) was characterized using nuclear magnetic resonance- and liquid chromatography-tandem mass spectrometry-based advanced lipid and lipoprotein analysis. An independent cohort of 1239 patients with PAD and CAD was used for validation. RESULTS: We found a significant difference in markers of inflammation as well as ceramide and phosphatidylcholine levels between patients with PAD and CAD. In contrast, basic lipid markers including total cholesterol, LDL cholesterol, HDL cholesterol, lipoprotein(a) or detailed lipoprotein profiles did not differ significantly between patients with PAD and CAD. Applying ratios and scores derived from ceramides and phosphatidylcholines further improved the discrimination between PAD and CAD. These significant differences were independent of body composition, from the status of smoking or type 2 diabetes mellitus, and also from apolipoprotein C-III and other inflammatory parameters which were different between CAD and PAD. CONCLUSION: The present study clearly suggests that PAD and CAD differ in terms of their ceramide- and phosphatidylcholine-based lipid patterns but not in lipoprotein characteristics.

Lipid parameters in patients with acute coronary syndromes versus stable coronary artery disease.

BACKGROUND: Differences in lipid parameters between patients with acute coronary syndromes (ACS) and patients with stable coronary artery disease (CAD) are unclear and are addressed in this study. METHODS: We enrolled 582 patients with angiographically proven stable CAD (of whom 26·9% had diabetes mellitus type 2 (T2DM)) and 182 patients with ACS (of whom 35·8% had T2DM). RESULTS: HDL cholesterol and apolipoprotein A1 levels were significantly lower in patients with ACS than in patients with CAD (46 ± 16 mg/dL vs. 50 ± 16 mg/dL, P < 0·001, and 139 ± 30 mg/dL vs. 155 ± 31 mg/dL, P < 0·001, respectively). Analysis of covariance (ancova) adjusting for age, gender, smoking, BMI, statin therapy, alcohol use, hypertension and diabetic state confirmed an independent impact of ACS on HDL cholesterol and apolipoprotein A1 levels (F = 24·1; P < 0·001). In contrast, total cholesterol, LDL cholesterol, non-HDL cholesterol and apolipoprotein B levels did not differ significantly between patients with ACS and patients with stable CAD. CONCLUSION: HDL cholesterol and apolipoprotein A1 levels are lower in patients with ACS than in patients with stable CAD.

Current Practices of Medication Plans in Austrian Patients Undergoing Coronary Angiography: An In-Depth Analysis.

A complete medication plan (MPlan) increases medication safety and adherence and is crucial in care transitions. Countries that implemented a standardized MPlan reported benefits on patients' understanding and handling of their medication. Austria lacks such a standardization, with no available data on the issue. Objective: This study aimed to investigate the current state of all medication documentations (MDocs) at hospital admission in a population at high risk for polypharmacy in Austria. Methods: We enrolled 512 consecutive patients undergoing elective coronary angiography. Their MDocs and medications were recorded at admission. MDocs were categorized, whereby a MPlan was defined as a tabular list including medication name, dose, route, frequency and patient name. Results: Out of 485 patients, 55.1% had an MDoc (median number of drugs: 6, range 2-17), of whom 24.7% had unstructured documentation, 18.0% physicians' letters and 54.3% MPlans. Polypharmacy patients did not have a MDoc in 31.3%. Crucial information as the patients's name or the originator of the MDoc was missing in 31.1% and 20.4%, respectively. Patients with MDoc provided more comprehensive medication information (p = 0.019), although over-the-counter-medication was missing in 94.5% of MDocs. A discrepancy between the MPlan and current medication at admission existed in 64.4%. In total, only 10.7% of our patient cohort presented an MPlan that was in accordance with their current medication. Conclusion: The situation in Austria is far from a standardized MPlan generated in daily routine. Numerous MPlans do not represent the current medication and could pose a potential risk for the effectiveness and safety of pharmacotherapy.

25 years of lipid-lowering therapy: secular trends in therapy of coronary patients.

BACKGROUND AND AIM: Guidelines on dyslipidemia and lipid-lowering therapy (LLT) over the years recommend lower low-density lipoprotein cholesterol (LDL-C) goals by more intense therapy. Nevertheless, LDL­C has increased in the general population. Real-world trends of LLT medication as well as of LDL­C levels in cardiovascular high-risk patients are unclear. METHODS: From 2158 patients who were referred for elective coronary angiography, lipid medication was analyzed at admission in three cardiovascular observational studies (OS) over the last 25 years: OS1: 1999-2000, OS2: 2005-2008 and OS3: 2022-2023. The three studies were performed at the same cardiology unit of a tertiary care hospital in Austria. RESULTS: The proportion of patients without LLT significantly decreased from OS1 through OS2 to OS3 (49.4%, 45.6%, and 18.5%, respectively, ptrend < 0.001). Moreover, the percentage of patients under high-intensity statin treatment significantly increased from 0% to 5.1%, and 56.5% (ptrend < 0.001). Significantly more patients became treated by more than one compound (OS1: 1.8%, OS2: 1.6%, OS3: 31.2%; ptrend < 0.001). In the latest OS3, a trend to fixed-dose combination of statins with ezetimibe was observed. Mean LDL­C levels decreased from 129 mg/dL over 127 mg/dL to 83 mg/dL, respectively (ptrend < 0.001). Of the patients on high-intensity therapy 34% met the recent ESC/EAS goals (LDL-C < 55 mg/dL), but only 3% on non-intense therapy. CONCLUSION: We conclude that during the observational period of a quarter of a century, treatment intensity increased and LDL­C levels improved considerably. Guidelines apparently matter in this high-risk population and are considered by primary care physicians.

Insulin resistance is significantly associated with the metabolic syndrome, but not with sonographically proven peripheral arterial disease.

OBJECTIVE: Insulin resistance (IR) is the key feature of the metabolic syndrome (MetS); its association with peripheral arterial disease (PAD) is unclear. We hypothesized that IR is associated with both the MetS and sonographically proven PAD. METHODS: IR was determined by the Homeostasis Model Assessment (HOMA) index in 214 patients with sonographically proven PAD as well as in 197 controls, who did not have a history of PAD and in whom coronary artery disease was ruled out angiographically; the MetS was defined according to NCEP-ATPIII criteria. RESULTS: HOMA IR scores were significantly higher in MetS patients than in subjects without the MetS (5.9 ± 6.2 vs. 2.9 ± 3.9; p <0.001). However, HOMA IR did not differ significantly between patients with PAD and controls (4.2 ± 5.4 vs. 3.3 ± 4.3; p = 0.124). When both, the presence of MetS and of PAD were considered, HOMA IR was significantly higher in patients with the MetS both among those with PAD (6.1 ± 5.7 vs. 3.6 ± 5.2; p<0.001) and among controls (5.8 ± 6.8 vs. 2.3 ± 1.8; p <0.001), whereas it did not differ significantly between patients with PAD and controls among patients with the MetS (5.8 ± 6.8 vs. 6.1 ± 5.7; p = 0.587) nor among those without the MetS (2.3 ± 1.8 vs. 3.6 ± 5.2; p = 0.165). Similar results were obtained with the International Diabetes Federation definition of the MetS. CONCLUSION: IR is significantly associated with the MetS but not with sonographically proven PAD.

[Hospital diabetes management (Update 2023)]. / Diabetesmanagement im Krankenhaus (Update 2023).

This position statement presents the recommendations of the Austrian Diabetes Association for diabetes management of adult patients during inpatient stay. It is based on the current evidence with respect to blood glucose targets, insulin therapy and treatment with oral/injectable antidiabetic drugs during inpatient hospitalization. Additionally, special circumstances such as intravenous insulin therapy, concomitant therapy with glucocorticoids and use of diabetes technology during hospitalization are discussed.

[Overweight and obesity in adults: general principles of treatment and conservative management]. / Übergewicht und Adipositas bei Erwachsenen: allgemeine Behandlungsgrundsätze und konservatives Management.

The prevalence of overweight and obesity is steadily increasing in Austria as well as internationally. Obesity in particular is associated with multiple health risks, comorbidities, functional disability, and social stigma. Obesity is an independent, complex, chronic disease and should be treated as such by a multidisciplinary team of appropriately qualified personnel. In addition to recent international guidelines, this consensus paper outlines the overall principles of the management of overweight and obesity and provides guidance for the diagnosis and conservative treatment, focusing on lifestyle modifications and pharmacotherapy. Using the "5A" framework of behavioral health intervention, guidelines for a structured, pragmatic, and patient-centered medical care of adults with overweight or obesity are presented.

Single and joint impact of type 2 diabetes and of congestive heart failure on albuminuria: Data from subgroup analysis and data on moderate albuminuria.

We investigated 180 consecutive patients with congestive heart failure (CHF), of whom 83 had type 2 diabetes (T2DM) and 97 did not have diabetes as well as 223 controls without CHF, of whom 39 had T2DM and 184 did not have diabetes. Data was recorded by standardized interviews and by standardized examination protocols at our institution and were extracted from medical records. Here, we analyzed data on gender differences. Further, we examined the effect of CHF and T2DM on moderate albuminuria, i.e. on an albumin-creatinine ratio (ACR) of 30-300 mg/g. Table 1 shows baseline characteristics of our patients stratified by gender. Table 2 gives ACRs and prevalence rates of albuminuria separately for men and women. In logistic regression analyses adjusting for age, sex, body mass index, LDL cholesterol, history of smoking, history of hypertension, use of statins, ACE inhibitors/angiotensin II receptor blockers, aldosterone antagonists and other antihypertensive medication CHF and T2DM predicted the prevalence of albuminuria in a mutually independent manner in men (OR 4.93 [95% CI 1.76-13.85]; p = 0.002 and OR 2.38 [1.11-5.11]; p = 0.027, respectively), as well as in women (OR 5.66 [95% CI 1.76-18.20]; p = 0.004 and OR 3.53 [1.38-9.08]; p = 0.009, respectively). There was no significant interaction between gender and CHF or T2DM regarding the presence of albuminuria (p = 0.933 and 0.533, respectively), indicating that the association of CHF and T2DM with albuminuria did not differ significantly between men and women. In multivariate analysis of covariance, CHF and T2DM proved to be independent predictors of ACR in women after adjustment for age, sex, body mass index, LDL cholesterol, history of smoking, history of hypertension, use of statins, ACE inhibitors/angiotensin II receptor blockers, aldosterone antagonists and other antihypertensive medication (F = 5.38; p = 0.022 and F = 4.95; p = 0.028, respectively); for men the corresponding F-values were 2.70; p = 0.102 and 3.12; p = 0.079, respectively. There was no significant interaction between gender and CHF or T2DM regarding ACR (p = 0.464 and 0.202, respectively), indicating that the association of CHF and T2DM with the ACR did not differ significantly between men and women. Regarding moderate albuminuria, both CHF and T2DM predicted moderate albuminuria adjusted in a mutually independent manner after the adjustments described above, with ORs of 4.75 [95% CI 2.16-10.45]; p< 0.001 and OR 2.08 [1.13-3.83]; p=0.018, respectively. The data set presented here could be reused with similar patient cohorts for pooled analysis.

Downhill hiking improves low-grade inflammation, triglycerides, body weight and glucose tolerance.

Exercise is a well-established tool for cardiovascular risk reduction. Particularly eccentric exercise, which essentially means walking downwards could favour more people becoming physically active. With the present controlled study, we tested the hypothesis that eccentric exercise can improve insulin sensitivity, triglyceride handling, body mass index, glucose tolerance and inflammation. We allocated 127 healthy sedentary individuals to one of two groups: (i) an active group of 102 individuals walking downwards a predefined route three to five times per week over two months, covering a difference in altitude of 540 m; for the upward route a cable car was used, for which adherence was recorded electronically and (ii) a matched control group of 25 individuals who stayed sedentary. Fasting and postprandial metabolic profiles were obtained at baseline and after two months. Compared to baseline, eccentric exercise significantly improved HOMA insulin resistance (1.94 ± 1.65 vs. 1.71 ± 1.36 (µU-1 ml) × ((mmol/l)-122.5); p = 0.038) and resulted in a decrease in fasting glucose (97 ± 15 vs. 94 ± 9 mg dl-1; p = 0.025) and glucose tolerance (238 ± 50 vs. 217 ± 47 mg dl-1 h-1; p < 0.001), whereas these parameters did not change significantly in the control group. Eccentric exercise significantly improved triglyceride tolerance (1923 ± 1295 vs. 1670 ± 1085 mg dl-1 h-1; p = 0.003), whereas triglyceride tolerance remained unchanged in the control group (p = 0.819). Furthermore, body mass index (27.7 ± 4.3 vs. 27.4 ± 4.3 kg m-2; p = 0.003) and C-reactive protein (0.27 ± 0.42 vs. 0.23 ± 0.25 mg dl-1; p = 0.031) were significantly lowered in the eccentric exercise group but not in the control group. Downhill walking, a type of exercise is a promising unusual exercise modality with favorable effects on body mass index, insulin action, on postprandial glucose and triglyceride handling and on C-reactive protein.ClinicalTrials.gov Identifier: NCT00386854.

Type 2 diabetes and the risk of cardiovascular events in peripheral artery disease versus coronary artery disease.

INTRODUCTION: The prevalence of type 2 diabetes mellitus (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD. How cardiovascular risk compares between PAD and CAD patients when analyses are stratified by the presence of type 2 diabetes is unclear and is addressed in the present study. RESEARCH DESIGN AND METHODS: We prospectively recorded major cardiovascular events (MACE; ie, cardiovascular death, myocardial infarction or stroke) over 10.0±4.7 years in 923 patients with stable CAD, of whom 26.7% had T2DM and in 292 patients with PAD, of whom 42.1% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM-; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM-; n=169) and PAD patients with T2DM (PAD/T2DM+; n=123). RESULTS: The event rate for MACE increased over our four investigated groups: it was lowest in CAD/T2DM- patients (2.52 events per 100 person-years). It was significantly higher in CAD/T2DM+ patients (3.96 events per 100 person-years; p<0.001), in PAD/T2DM- patients (3.68 events per 100 person-years; p=0.022), and in PAD/T2DM+ patients (7.10 events per 100 person-years; p<0.001), who in turn were at a higher risk than CAD/T2DM+ or PAD/T2DM- patients (p=0.001 and p<0.001, respectively). Cox regression analysis after multivariate adjustment showed that the presence of T2DM (HR=1.44 (95% CI 1.09 to 1.92); p=0.012) and the presence of PAD versus CAD (HR=1.48 (95% CI 1.15 to 1.91); p=0.002) were mutually independent predictors of cardiovascular events. CONCLUSIONS: In conclusion, our data show that T2DM as well as the presence of PAD versus CAD are mutually independent predictors of MACE. Patients with both PAD and T2DM are at an exceedingly high risk of cardiovascular events.

Adherence to statin therapy favours survival of patients with symptomatic peripheral artery disease.

AIMS: We hypothesized that adherence to statin therapy determines survival in patients with peripheral artery disease (PAD). METHODS AND RESULTS: Single-centre longitudinal observational study with 691 symptomatic PAD patients. Mortality was evaluated over a mean follow-up of 50 ± 26 months. We related statin adherence and low-density lipoprotein cholesterol (LDL-C) target attainment to all-cause mortality. Initially, 73% of our PAD patients were on statins. At follow-up, we observed an increase to 81% (P < 0.0001). Statin dosage, normalized to simvastatin 40 mg, increased from 50 to 58 mg/day (P < 0.0001), and was paralleled by a mean decrease of LDL-C from 97 to 82 mg/dL (P < 0.0001). The proportion of patients receiving a high-intensity statin increased over time from 38% to 62% (P < 0.0001). Patients never receiving statins had a significant higher mortality rate (31%) than patients continuously on statins (13%) or having newly received a statin (8%; P < 0.0001). Moreover, patients on intensified statin medication had a low mortality of 9%. Those who terminated statin medication or reduced statin dosage had a higher mortality (34% and 20%, respectively; P < 0.0001). Multivariate analysis showed that adherence to or an increase of the statin dosage (both P = 0.001), as well as a newly prescribed statin therapy (P = 0.004) independently predicted reduced mortality. CONCLUSION: Our data suggest that adherence to statin therapy is associated with reduced mortality in symptomatic PAD patients. A strategy of intensive and sustained statin therapy is recommended.

The LDL-C/ApoB ratio predicts major cardiovascular events in patients with established atherosclerotic cardiovascular disease.

BACKGROUND AND AIMS: The low density lipoprotein cholesterol to Apolipoprotein B (LDL-C/ApoB) ratio is a validated proxy for low density lipoprotein (LDL) particle size that can be easily calculated from a standard lipid/apolipoprotein profile. Whether it is predictive of cardiovascular events in patients with established atherosclerosis is not known and is addressed in the present investigation. METHODS: We determined the LDL-C/ApoB ratio in a cohort of 1687 subjects with established atherosclerosis. Prospectively, major cardiovascular events (MACE) including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a period of 9.9 ± 4.6 years. The study covers >16,000 patient-years. RESULTS: At baseline, the LDL-C/ApoB ratio was 1.36 ± 0.28 in our cohort. During follow up, a total of 558 first MACE were recorded. The LDL-C/ApoB ratio predicted MACE in univariate Cox proportional hazard analysis (HR 0.90 [0.82-0.98]; p = 0.014); this finding was confirmed after adjustment for age, gender, intensity of statin treatment, hypertension, history of smoking, type 2 diabetes, body mass index and ApoB (HR 0.87 [0.78-0.97]; p = 0.013). CONCLUSIONS: The LDL-C/ApoB ratio is independently predictive of MACE in subjects with established atherosclerosis.

Single and joint impact of type 2 diabetes and of congestive heart failure on albuminuria.

AIMS: Albuminuria is a characteristic feature of diabetic nephropathy, and urine albumin excretion is also increased in patients with congestive heart failure (CHF). However, no data are available on the single and joint associations of type 2 diabetes mellitus (T2DM) and CHF with albuminuria. This issue was addressed in the present study. METHODS: We investigated 4 groups of patients: 180 patients with CHF, of whom 83 had T2DM (CHF+/T2DM+) and 97 did not have diabetes (CHF+/T2DM-) and 223 controls without CHF, of whom 39 had T2DM (CHF-/T2DM+) and 184 did not have diabetes (CHF-/T2DM-). RESULTS: The albumin-creatinine ratio (ACR) was 9.2 [5.7-16.9] mg/g in CHF-/T2DM- patients. Compared to this group it was higher in CHF-/T2DM+ patients (16.1 [7.7-27.8] mg/g; p = 0.004), in CHF+/T2DM- patients (22.0 [9.0-76.8] mg/g; p < 0.001) and in CHF+/T2DM+ patients (66.2 [16.0-177.0] mg/g; p < 0.001), in whom in turn it was higher than in CHF-/T2DM+ (p < 0.001) or in CHF+/T2DM- (p = 0.001) patients. The ACR did not differ significantly between CHF-/T2DM+ and CHF+/T2DM- patients (p = 0.188). In multivariate analysis of covariance, CHF and T2DM proved to be independent predictors of ACR after multivariate adjustment (F = 5.68; p = 0.018 and F = 4.79; p = 0.029, respectively). CONCLUSIONS: We conclude that T2DM and CHF are mutually independent determinants of albuminuria.

Value of total cholesterol readings earlier versus later in life to predict cardiovascular risk.

BACKGROUND: Prognostic implications of blood cholesterol may differ at different stages of life. This cohort study compares the value of total cholesterol (TC) readings earlier versus later in life for the prediction of coronary atherosclerosis, cardiovascular events, and cardiovascular death. METHODS: In a cardiovascular observation study (CVOS) we performed coronary angiography and prospectively recorded cardiovascular events in 1090 patients over up to 19 years. These patients had participated in a health survey (HS) 15 years prior to the CVOS baseline. TC was measured twice, first at the earlier HS and then later at CVOS recruiting. FINDINGS: Patients in the highest versus the lowest TC-category of the HS had an OR of 4.30 [2.41-7.65] for significant CAD at angiography, a HR of 1.74 [1.10-2.76] for cardiovascular events, and a HR of 7.55 [1.05-54.49] for cardiovascular death after multivariate adjustment. In contrast, TC as measured at the baseline of the CVOS was neither significantly associated with significant CAD (OR= 0.75 [0.49-1.13]) nor with cardiovascular events or death during follow-up (HR= 0.86 [0.62-1.18] and 0.79 [0.41-1.53], respectively). Moreover, the ESC/EAS-SCORE was found to be more powerful in predicting cardiovascular mortality when using earlier instead of later TC, with a continuous net reclassification improvement of 0.301 (p<0.001). INTERPRETATION: Early measurement not only enables early intervention in keeping with the concept of lifelong exposure to atherogenic lipoproteins. These data also suggest that cardiovascular risk prediction is more accurate if using earlier in life TC readings. FUNDING: The present study did not receive any particular funding.

Usefulness of Handgrip Strength to Predict Mortality in Patients With Coronary Artery Disease.

Handgrip strength (HGS) is a validated and simple technique to estimate skeletal muscular strength. Whether HGS is a predictor of overall mortality in patients with established coronary artery disease (CAD) is not known, this question is therefore addressed in the present study. We prospectively investigated a cohort of 691 patients with angiographically proven CAD. HGS was measured at baseline, and all-cause death as well as cardiovascular events was recorded over a period of up to 12 years. During a follow-up time of 9.2 ± 3.1 years, 31.3% (n = 216) of the study participants died. Further, 27.8% (n = 192) suffered major cardiovascular events and 56.6% (n = 391) any cardiovascular event. Cox proportional hazard model analysis showed a reduced mortality risk with higher HGS univariately (hazard ratio [HR] for each 5 kg increase in HGS 0.87 [95% confidence interval 0.82 to 0.92]; p <0.001), after adjustment for age and gender (HR 0.86 [0.79 to 0.94]; p = 0.001), and after further adjustment for conventional cardiovascular risk factors (HR 0.86 [0.79 to 0.94]; p = 0.001). Similarly, high HGS was protective of major cardiovascular events as well as of total cardiovascular events (HRs in the fully adjusted model 0.86 [0.78 to 0.94]; p = 0.002 and 0.89 [0.83 to 0.96]; p = 0.002, respectively). From these data, we conclude that HGS is an independent predictor of overall survival and of cardiovascular events in patients with CAD.

Type 2 diabetes mellitus is a strong predictor of LDL cholesterol target achievement in patients with peripheral artery disease.

BACKGROUND AND AIMS: Patients with peripheral artery disease (PAD) are at a very high risk of cardiovascular events and strongly benefit from lowering LDL cholesterol (LDL-C); updated European Society of Cardiology guidelines recommend an LDL-C target of at least <55 mg/dl for these patients. Whether the presence of type 2 diabetes (T2DM) affects LDL-C target achievement in PAD patients is unknown and is addressed in the present study. METHODS: We investigated an unselected consecutive series of 319 patients with sonographically proven PAD, of whom 136 (42.6%) had T2DM. RESULTS: The LDL-C target of <55 mg/dl was met by 8.1% of T2DM patients and by 2.2% of non-diabetic patients (p = 0.014); LDL-C was <70 mg/dl in 22.8% of patients with T2DM and in 9.8% of non-diabetic patients (p = 0.002). Logistic regression analysis showed that the presence of T2DM was an independent and strong predictor of LDL-C target achievement after multivariate adjustment including age, gender, potency adjusted statin use, BMI, smoking, hypertension and other lipid-modifying therapy for the <55 mg/dl target (OR 3.58 [1.08-11.90]; p = 0.038) as well as for the <70 mg/dl target (OR 2.78 [1.40-5.35]; p = 0.003). CONCLUSION: We conclude that T2DM is a strong and independent predictor of LDL-C target achievement among PAD patients; however, also among PAD patients with T2DM only a minority meets the current target of <55 mg/dl and most patients do not even have an LDL-C < 70 mg/dl.

The age of randomized clinical trials: three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid and diabetes trials.

Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiovascular (CV) therapy. The cornerstone of RCTs is the recording of hard clinical endpoints instead of surrogates. It is important to select an appropriate endpoint. Efficacy endpoints must be clinically relevant and can be hierarchically divided. A very interesting innovation in endpoint acquisition is the total event paradigm.

[Hospital diabetes management (Update 2019)]. / Diabetesmanagement im Krankenhaus (Update 2019).

This position statement presents the recommendations of the Austrian Diabetes Association for diabetes management of adult patients during inpatient stay. It is based on the current evidence with respect to blood glucose targets, insulin therapy and treatment with oral antidiabetic drugs during inpatient hospitalization. Additionally, special circumstances such as intravenous insulin therapy, concomitant therapy with glucocorticoids and use of diabetes technology during hospitalization are discussed.

Are SGLT2 polymorphisms linked to diabetes mellitus and cardiovascular disease? Prospective study and meta-analysis.

Inhibition of the sodium glucose co-transporter 2 (SGLT2) reduces cardiovascular morbidity, and mortality in patients with type 2 diabetes mellitus (T2DM) with atherosclerotic, cardiovascular disease. So far, a link between common genetic variations of the SGLT2 encoding gene SLC5A2 and glucose homeostasis as well as cardiovascular disease has not been established. The present study, therefore, aimed to investigate SLC5A2 single nucleotide polymorphisms (SNPs) in relation to type 2 diabetes and coronary artery disease (CAD) and prospectively the incidence of cardiovascular events. We genotyped the SLC5A2 tagging SNPs rs9934336, rs3813008, and rs3116150 in a total of 1684 high risk cardiovascular patients undergoing coronary angiography, including 400 patients with T2DM. Additionally, we performed a meta-analysis combining results from the present study and the literature. Variant rs9934336 was significantly associated with decreased HbA1c (P = 0.023). Further, rs9934336 was significantly inversely associated with the presence of T2DM in univariate (OR = 0.82 [0.68-0.99]; P = 0.037) as well as in multivariate analysis (OR = 0.79 [0.65-0.97]; P = 0.023). The association between rs9934336 and T2DM was confirmed in a meta-analysis including results from two previous observations which by themselves had failed to show a significant association of the polymorphism with T2DM (OR = 0.86 [0.78-0.95]; P = 0.004). Polymorphisms rs3813008 and rs3116150 were associated neither with glycemic parameters nor with T2DM. None of the SNPs tested was significantly associated with the baseline presence of CAD or the incidence of cardiovascular events. We conclude that genetic variation within the SLC5A2 gene locus is significantly related to the manifestation of T2DM.