Publications by authors named "Heinz Drexel"

195 Publications

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology.

Eur J Heart Fail 2022 Jan;24(1):143-168

Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.
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http://dx.doi.org/10.1002/ejhf.2351DOI Listing
January 2022

Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology.

Eur J Prev Cardiol 2022 Jan 27. Epub 2022 Jan 27.

Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed.
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http://dx.doi.org/10.1093/eurjpc/zwab147DOI Listing
January 2022

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

Data Brief 2022 Feb 10;40:107817. Epub 2022 Jan 10.

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, Feldkirch AT-6800, Austria.

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];  = 0.002 and OR 2.38 [1.11-5.11];  = 0.027, respectively), as well as in women (OR 5.66 [95% CI 1.76-18.20];  = 0.004 and OR 3.53 [1.38-9.08];  = 0.009, respectively). There was no significant interaction between gender and CHF or T2DM regarding the presence of albuminuria ( = 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 ( = 5.38;  = 0.022 and  = 4.95;  = 0.028, respectively); for men the corresponding -values were 2.70;  = 0.102 and 3.12;  = 0.079, respectively. There was no significant interaction between gender and CHF or T2DM regarding ACR ( = 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.
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http://dx.doi.org/10.1016/j.dib.2022.107817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762350PMC
February 2022

PCSK9 inhibition in patients with heart failure: neutral or harmful intervention?

Eur Heart J 2022 Jan 13. Epub 2022 Jan 13.

Department of Internal Medicine, County Hospital Bregenz, Carl-Pedenz-Strasse 2, A-6900 Bregenz, Austria.

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http://dx.doi.org/10.1093/eurheartj/ehab913DOI Listing
January 2022

Elevated levels of apolipoprotein D predict poor outcome in patients with suspected or established coronary artery disease.

Atherosclerosis 2022 Jan 20;341:27-33. Epub 2021 Dec 20.

Institute of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Electronic address:

Background And Aims: Apolipoprotein D (apoD) is a lipocalin exerting neuroprotective effects. However, the relevance of apoD in respect to cardiovascular risk is largely unexplored. Therefore, this study aimed to evaluate the ability of apoD to predict future all-cause mortality, cardiovascular mortality, and cardiovascular events.

Methods: Serum apoD levels were measured in a cohort of 531 Caucasian individuals who underwent coronary angiography (356 males, 175 females; mean age 65 ± 10 years). Fatal and non-fatal events were recorded over a median follow-up period of 5.8 years.

Results: ApoD concentrations at baseline correlated significantly with age, presence of the metabolic syndrome, body mass index, lipoprotein levels, fasting glucose, and estimated glomerular filtration rate. Kaplan-Meier curve analyses by gender-stratified quartiles of apoD revealed that the cumulative incidence rates of mortality and cardiovascular events become higher with increasing apoD levels. The adjusted hazard ratios for participants in the highest quartile of apoD compared to those in the lowest quartile were 4.00 (95% confidence interval [CI] 1.49-10.74) for overall mortality, 5.47 (95% CI 1.20-25.00) for cardiovascular mortality, and 2.52 (95% CI 1.28-5.00) for cardiovascular events.

Conclusions: High circulating levels of apoD are an indicator of poor prognosis in patients with suspected or established coronary artery disease.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.12.011DOI Listing
January 2022

Lipid lowering therapy in primary and secondary prevention in Austria: are LDL-C goals achieved? : Results from the DA VINCI study.

Wien Klin Wochenschr 2021 Dec 6. Epub 2021 Dec 6.

Imperial Centre for Cardiovascular Disease Prevention and Imperial Clinical Trials Unit, Imperial College London, London, UK.

Background: Cardiovascular disease (CVD) is the most frequent cause of death in Austria. The European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT) in patients at high or very high CV risk. Lipid management and achievement of low-density lipoprotein cholesterol (LDL-C) goals in Austria have not recently been assessed.

Methods: Subgroup analysis for Austria of a European 18 country, cross-sectional, observational study. Patients received LLT for primary (PP) or secondary prevention (SP). Data including LLT in the preceding 12 months and most recent LDL‑C were collected during a single visit between June 2017 and November 2018. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL‑C goal while receiving stabilized LLT was assessed.

Results: A total of 293 patients were enrolled from 8 Austrian sites, of which 200 (PP = 104, SP = 96) received stabilized LLT at the LDL‑C measurement date. Overall, 58% (71% PP, 43% SP) and 38% (52% PP, 23% SP) achieved the risk-based 2016 and 2019 goals, respectively. Most patients received moderate-intensity statin monotherapy (46%), while 34% used high-intensity statin monotherapy. Combination therapy of moderate/high-intensity statin with ezetimibe (12%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors with statin ± ezetimibe (1%), was used infrequently.

Conclusion: The current Austrian routine lipid management using mainly moderate-intensity or high-intensity statin monotherapy is insufficient to attain ESC/EAS guideline goals, in particular the more stringent 2019 recommendations, a situation comparable to other participating European countries. In addition to switching to and optimizing doses of high-intensity statins, a combination with ezetimibe or PCSK9 inhibitors will be needed in many cases.
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http://dx.doi.org/10.1007/s00508-021-01978-wDOI Listing
December 2021

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

BMJ Open Diabetes Res Care 2021 11;9(2)

VIVIT, Vorarlberg Institute of Vascular Investigation and Treatment, Feldkirch, Vorarlberg, Austria

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.
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http://dx.doi.org/10.1136/bmjdrc-2021-002407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593703PMC
November 2021

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

J Diabetes Complications 2021 12 12;35(12):108046. Epub 2021 Sep 12.

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, AT-6800 Feldkirch, Austria; Private University of the Principality of Liechtenstein, Dorfstrasse 24, FL-9495 Triesen, Liechtenstein; Department of Medicine I, Academic Teaching Hospital Feldkirch, Carinagasse 47, AT-6800 Feldkirch, Austria; Drexel University College of Medicine, 2900 W Queen Ln, PA 19129, Philadelphia, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.108046DOI Listing
December 2021

Combined Use of Serum Uromodulin and eGFR to Estimate Mortality Risk.

Front Med (Lausanne) 2021 8;8:723546. Epub 2021 Sep 8.

Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Serum uromodulin (sUmod) shows a strong direct correlation with eGFR in patients with impaired kidney function and an inverse association with mortality. However, there are patients in whom only one of both markers is decreased. Therefore, we aimed to investigate the effect of marker discordance on mortality risk. sUmod and eGFR were available in 3,057 participants of the Ludwigshafen Risk and Cardiovascular Health study and 529 participants of the VIVIT study. Both studies are monocentric prospective studies of patients that had been referred for coronary angiography. Participants were categorized into four groups according to the median values of sUmod (LURIC: 146 ng/ml, VIVIT: 156) and eGFR (LURIC: 84 ml/min/1.73 m, VIVIT: 87). In 945 LURIC participants both markers were high (UHGH), in 935 both were low (ULGL), in 589 only eGFR (UHGL), and in 582 only sUmod (ULGH) was low. After balancing the groups for cardiovascular risk factors, hazard ratios (95%CI) for all-cause mortality as compared to UHGH were 2.03 (1.63-2.52), 1.43 (1.13-1.81), and 1.32 (1.03-1.69) for ULGL, UHGL, and ULGH, respectively. In VIVIT, HRs were 3.12 (1.38-7.08), 2.38 (1.01-5.61), and 2.06 (0.81-5.22). Adding uromodulin to risk prediction models that already included eGFR as a covariate slightly increased the Harrell's C and significantly improved the AUC in LURIC. In UHGL patients, hypertension, heart failure and upregulation of the renin-angiotensin-aldosterone-system seem to be the driving forces of disease development, whereas in ULGH patients metabolic disturbances might be key drivers of increased mortality. In conclusion, SUmod/eGFR subgroups mirror distinct metabolic and clinical patterns. Assessing sUmod additionally to creatinine or cystatin C has the potential to allow a more precise risk modeling and might improve risk stratification.
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http://dx.doi.org/10.3389/fmed.2021.723546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455921PMC
September 2021

Challenges in cardiovascular pharmacogenomics implementation: a viewpoint from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

Eur Heart J Cardiovasc Pharmacother 2022 Jan;8(1):100-103

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Pharmacogenomics promises to advance cardiovascular therapy, but there remain pragmatic barriers to implementation. These are particularly important to explore within Europe, as there are differences in the populations, availability of resources, and expertise, as well as in ethico-legal frameworks. Differences in healthcare delivery across Europe present a challenge, but also opportunities to collaborate on pharmacogenomics implementation. Clinical workforce upskilling is already in progress but will require substantial input. Digital infrastructure and clinical support tools are likely to prove crucial. It is important that widespread implementation serves to narrow rather than widen any existing gaps in health equality between populations. This viewpoint supplements the working group position paper on cardiovascular pharmacogenomics to address these important themes.
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http://dx.doi.org/10.1093/ehjcvp/pvab063DOI Listing
January 2022

Comparison of recent ceramide-based coronary risk prediction scores in cardiovascular disease patients.

Eur J Prev Cardiol 2021 Aug 21. Epub 2021 Aug 21.

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, A-6800 Feldkirch, Austria.

Aim: Cholesterol-based risk prediction is often insufficient in cardiovascular disease (CVD) patients. Ceramides are a new kind of biomarkers for CVD. The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses only circulating ceramide levels, determined by coupled liquid chromatography-mass spectrometry, to allocate patients into one of four risk categories. This test has recently been modified (CERT2) by additionally including phosphatidylcholine levels.

Methods And Results: In this observational cohort study, we have recruited 999 Austrian patients with CVD and followed them for up to 13 years. We found that CERT and CERT2 both predicted cardiovascular events, cardiovascular mortality, and overall mortality. CERT2 had the higher performance compared to CERT and also to the recent cardiovascular risk score of the ESC/EAS guidelines (Systematic COronary Risk Evaluation (SCORE)) for low-risk European countries. Combining CERT2 with the ESC/EAS-SCORE, predictive capacity was further increased leading to a hazard ratio of 3.58 (2.02-6.36; P < 0.001) for cardiovascular events, 11.60 (2.72-49.56; P = 0.001) for cardiovascular mortality, and 9.86 (4.23-22.99; P < 0.001) for overall mortality when patients with very high risk (category 4) were compared to those with low risk (category 1). The use of the combined score instead of the ESC/EAS-SCORE significantly improved the predictive power according to the integrated discrimination improvement index (P = 0.004).

Conclusion: We conclude that CERT and CERT2 are powerful predictors of cardiovascular events, cardiovascular mortality, and overall mortality in CVD patients. Including phosphatidylcholine to a ceramide-based score increases the predictive performance and is best in combination with classical risk factors as used in the ESC/EAS-SCORE.
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http://dx.doi.org/10.1093/eurjpc/zwab112DOI Listing
August 2021

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

J Intern Med 2021 12 10;290(6):1249-1263. Epub 2021 Sep 10.

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.

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.
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http://dx.doi.org/10.1111/joim.13368DOI Listing
December 2021

Antithrombotic therapies in aortic and peripheral arterial diseases in 2021: a consensus document from the ESC working group on aorta and peripheral vascular diseases, the ESC working group on thrombosis, and the ESC working group on cardiovascular pharmacotherapy.

Eur Heart J 2021 10;42(39):4013-4024

Cardiothoracic and Vascular Department, Azienda OspedalieroUniversitaria Pisana, Pisa, Italy.

The aim of this collaborative document is to provide an update for clinicians on best antithrombotic strategies in patients with aortic and/or peripheral arterial diseases. Antithrombotic therapy is a pillar of optimal medical treatment for these patients at very high cardiovascular risk. While the number of trials on antithrombotic therapies in patients with aortic or peripheral arterial diseases is substantially smaller than for those with coronary artery disease, recent evidence deserves to be incorporated into clinical practice. In the absence of specific indications for chronic oral anticoagulation due to concomitant cardiovascular disease, a single antiplatelet agent is the basis for long-term antithrombotic treatment in patients with aortic or peripheral arterial diseases. Its association with another antiplatelet agent or low-dose anticoagulants will be discussed, based on patient's ischaemic and bleeding risk as well therapeutic paths (e.g. endovascular therapy). This consensus document aims to provide a guidance for antithrombotic therapy according to arterial disease localizations and clinical presentation. However, it cannot substitute multidisciplinary team discussions, which are particularly important in patients with uncertain ischaemic/bleeding balance. Importantly, since this balance evolves over time in an individual patient, a regular reassessment of the antithrombotic therapy is of paramount importance.
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http://dx.doi.org/10.1093/eurheartj/ehab390DOI Listing
October 2021

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

Sci Rep 2021 07 15;11(1):14503. Epub 2021 Jul 15.

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.

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 ml) × ((mmol/l)22.5); p = 0.038) and resulted in a decrease in fasting glucose (97 ± 15 vs. 94 ± 9 mg dl; p = 0.025) and glucose tolerance (238 ± 50 vs. 217 ± 47 mg dl h; 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 h; 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; p = 0.003) and C-reactive protein (0.27 ± 0.42 vs. 0.23 ± 0.25 mg dl; 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.
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http://dx.doi.org/10.1038/s41598-021-93879-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282605PMC
July 2021

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

Atherosclerosis 2021 07 1;329:44-49. Epub 2021 Jun 1.

Department of Medicine I, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria; Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, 6800, Feldkirch, Austria; Private University in the Principality of Liechtenstein, Dorfstraße 24, 9495, Triesen, Liechtenstein.

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.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.05.010DOI Listing
July 2021

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

EBioMedicine 2021 May 14;67:103371. Epub 2021 May 14.

Agency for Preventive and Social Medicine, Bregenz, Austria.

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.
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http://dx.doi.org/10.1016/j.ebiom.2021.103371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138461PMC
May 2021

Update on management of hypokalaemia and goals for the lower potassium level in patients with cardiovascular disease: a review in collaboration with the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

Eur Heart J Cardiovasc Pharmacother 2021 Nov;7(6):557-567

Department of Clinical Research, North Zealand University Hospital, Dyrehavevej 48, 3400, Hillerød, Denmark.

Hypokalaemia is common in patients with cardiovascular disease. In this review, we emphasize the importance of tight potassium regulation in patients with cardiovascular disease based on findings from observational studies. To enhance the understanding, we also describe the mechanisms of potassium homeostasis maintenance, the most common causes of hypokalaemia and present strategies for monitoring and management of low potassium levels. We propose elevation of potassium in asymptomatic patients with lower normal concentrations and concurrent cardiovascular disease. These proposals are intended to assist clinicians until more evidence is available.
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http://dx.doi.org/10.1093/ehjcvp/pvab038DOI Listing
November 2021

Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: A statement from a European Atherosclerosis Society Task Force.

Atherosclerosis 2021 05 13;325:99-109. Epub 2021 Apr 13.

Department of Pharmacological and Biomolecular Sciences, Universita' degli Studi di Milano, Milan, and IRCCS MultiMedica, Milan, Italy. Electronic address:

Background And Aims: This European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients.

Methods: Evidence-based review.

Results: Statin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-high-risk patients with mild to moderately elevated TG levels (>2.3 and < 5.6 mmol/L [>200 and < 500 mg/dL) on a statin, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks. Combination with fenofibrate may be considered for both macro- and microvascular benefits in patients with type 2 diabetes mellitus.

Conclusions: This guidance aims to improve real-world use of guideline-recommended combination lipid modifying treatment.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.039DOI Listing
May 2021

Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients.

Sci Rep 2021 03 24;11(1):6761. Epub 2021 Mar 24.

Onkologie Ravensburg, 88212, Ravensburg, Germany.

Mutational analysis of circulating tumour (ct) DNA holds promise as an effective tool to predict the course of metastatic breast cancer (MBC). In the present study we used targeted next generation sequencing of ctDNA to evaluate the impact of cancer driven mutations on the prognosis of MBC. The study included 59 oestrogen receptor-positive (ER+), HER2-negative MBC patients. Sequencing analysis was performed in ESR1, PIK3CA, ERBB2, PTEN, TP53, KRAS, HRAS, NRAS, and AR. At baseline, patients started receiving either chemotherapy (34%; n = 20) or cyclin-dependent kinase 4/6 inhibitor therapy in combination with endocrine therapy (CDK4/6i+ET; 66%; n = 39). Overall, 64.4% (n = 38) of the patients carried at least one pathogenic or likely-pathogenic mutation. Number of ctDNA mutations was significantly linked with worse progression free survival (PFS; p = 0.003) and overall survival (OS; p = 0.007). Furthermore, ctDNA load, defined by the number of mutant ctDNA molecules per mL plasma, significantly correlated with PFS (p < 0.001) and OS (p = 0.001). Furthermore, mutational status of ESR1 and TP53 significantly predicted PFS (p = 0.024 and p = 0.035, respectively) and OS (p < 0.001 and p = 0.035, respectively). These results emphasizes the clinical value of ctDNA mutational analysis in the management of advanced breast cancer.
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http://dx.doi.org/10.1038/s41598-021-86238-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990915PMC
March 2021

The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

Eur Heart J Cardiovasc Pharmacother 2022 Jan;8(1):85-99

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

There is a strong and ever-growing body of evidence regarding the use of pharmacogenomics to inform cardiovascular pharmacology. However, there is no common position taken by international cardiovascular societies to unite diverse availability, interpretation, and application of such data, nor is there recognition of the challenges of variation in clinical practice between countries within Europe. Aside from the considerable barriers to implementing pharmacogenomic testing and the complexities of clinically actioning results, there are differences in the availability of resources and expertise internationally within Europe. Diverse legal and ethical approaches to genomic testing and clinical therapeutic application also require serious thought. As direct-to-consumer genomic testing becomes more common, it can be anticipated that data may be brought in by patients themselves, which will require critical assessment by the clinical cardiovascular prescriber. In a modern, pluralistic and multi-ethnic Europe, self-identified race/ethnicity may not be concordant with genetically detected ancestry and thus may not accurately convey polymorphism prevalence. Given the broad relevance of pharmacogenomics to areas, such as thrombosis and coagulation, interventional cardiology, heart failure, arrhythmias, clinical trials, and policy/regulatory activity within cardiovascular medicine, as well as to genomic and pharmacology subspecialists, this position statement attempts to address these issues at a wide-ranging level.
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http://dx.doi.org/10.1093/ehjcvp/pvab018DOI Listing
January 2022

The Volatilomic Footprints of Human HGC-27 and CLS-145 Gastric Cancer Cell Lines.

Front Mol Biosci 2020 11;7:607904. Epub 2021 Jan 11.

Institute for Breath Research, University of Innsbruck, Dornbirn, Austria.

The presence of certain volatile biomarkers in the breath of patients with gastric cancer has been reported by several studies; however, the origin of these compounds remains controversial. studies, involving gastric cancer cells may address this problem and aid in revealing the biochemical pathways underlying the production and metabolism of gastric cancer volatile indicators. Gas chromatography with mass spectrometric detection, coupled with headspace needle trap extraction as the pre-concentration technique, has been applied to map the volatilomic footprints of human HGC-27 and CLS-145 gastric cancer cell lines and normal Human Stomach Epithelial Cells (HSEC). In total, 27 volatile compounds are found to be associated with metabolism occurring in HGC-27, CLS-145, and HSEC. Amongst these, the headspace concentrations of 12 volatiles were found to be reduced compared to those above just the cultivating medium, namely there was an observed uptake of eight aldehydes (2-methylpropanal, 2-methyl-2-propenal, 2-methylbutanal, 3-methylbutanal, hexanal, heptanal, nonanal, and benzaldehyde), three heterocyclic compounds (2-methyl-furan, 2-ethyl-furan, and 2-pentyl-furan), and one sulfur-containing compound (dimethyl disulphide). For the other 15 volatiles, the headspace concentrations above the healthy and cancerous cells were found to be higher than those found above the cultivating medium, namely the cells were found to release three esters (ethyl acetate, ethyl propanoate, and ethyl 2-methylbutyrate), seven ketones (2-pentanone, 2-heptanone, 2-nonanone, 2-undecanone, 2-tridecanone, 2-pentadecanone, and 2-heptadecanone), three alcohols (2-methyl-1-butanol, 3-methyl-1-butanol, and 2-ethyl-1-hexanol), one aromatic compound (toluene), and one sulfur containing compound [2-methyl-5-(methylthio) furan]. In comparison to HSEC, HGC-27 cancer cell lines were found to have significantly altered metabolism, manifested by an increased production of methyl ketones containing an odd number of carbons. Amongst these species, three volatiles were found exclusively to be produced by this cell line, namely 2-undecanone, 2-tridecanone, and 2-heptadecanone. Another interesting feature of the HGC-27 footprint is the lowered level of alcohols and esters. The CLS-145 cells exhibited less pronounced changes in their volatilomic pattern compared to HSEC. Their footprint was characterized by the upregulated production of esters and 2-ethyl-hexanol and downregulated production of other alcohols. We have therefore demonstrated that it is possible to differentiate between cancerous and healthy gastric cells using biochemical volatile signatures.
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http://dx.doi.org/10.3389/fmolb.2020.607904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874186PMC
January 2021

Improved Lipid Target Level Attainment in Patients with Peripheral Artery Disease.

Curr Vasc Pharmacol 2021 ;19(6):634-642

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.

Background: Patients with peripheral artery disease (PAD) fall under the category of a very high cardiovascular risk. Although consequent lipid-lowering therapy (LLT) is advised, only sparse data on attained target level in PAD exists.

Objectives: We aimed to analyse contemporary guideline recommendations for LLT in symptomatic PAD patients.

Methods: A monocentric, prospective, observational study involving 200 symptomatic PAD patients was conducted. Guideline target level attainment and LLT were analysed between 2017 and 2019.

Results: Overall, 78.5% of the patients were on statin therapy, mainly of high intensity, with atorvastatin in 50% and rosuvastatin in 33% of the cases. The average statin dosage adjusted for simvastatin was 55 mg/d. Low density lipoprotein-cholesterol (LDL-C) was <1.8 mmol/L in 53% and <1.4 mmol/L in 34% of the cases. Mean LDL-C levels were at 1.85 ± 0.88 mmol/L. We observed no difference in the treatment and the target level attainment of patients with a stable PAD (intermittent claudication) or chronic critical PAD. However, patients with ≥ 1 vascular region affected (i.e., coronary and/or cerebrovascular) were treated more intensively and had lower LDL-C levels than patients with PAD alone.

Conclusion: It appears that there are more awareness and improvement of previously documented undertreatment of LDL-C levels in symptomatic PAD patients. Although statin treatment is initiated in the majority of patients, our findings call for a continuously intensified LLT in symptomatic PAD patients.
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http://dx.doi.org/10.2174/1570161119666210111123621DOI Listing
January 2022

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

Eur Heart J Cardiovasc Pharmacother 2021 Sep;7(5):453-459

Department of Medical Statistics, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK.

This review article aims to explain the important issues that data safety monitoring boards (DSMB) face when considering early termination of a trial and is specifically addressed to the needs of clinical and research cardiologists. We give an insight into the overall background and then focus on the three principal reasons for stopping trials, i.e. efficacy, futility, and harm. The statistical essentials are also addressed to familiarize clinicians with the key principles. The topic is further highlighted by numerous examples from lipid trials and antithrombotic trials. This is followed by an overview of regulatory aspects, including an insight into industry-investigator interactions. To conclude, we summarize the key elements that are the basis for a decision to stop a randomized clinical trial (RCT).
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http://dx.doi.org/10.1093/ehjcvp/pvaa126DOI Listing
September 2021

Potentially Inappropriate Prescriptions in Heart Failure with Reduced Ejection Fraction (PIP-HFrEF).

Eur Heart J Cardiovasc Pharmacother 2020 Sep 17. Epub 2020 Sep 17.

Centre of Clinical and Experimental Medicine, IRCCS San Raffaele Pisana, Rome, Italy.

Heart failure (HF) is a chronic debilitating and potentially life-threatening condition. Heart Failure patients are usually at high risk of polypharmacy and consequently, potentially inappropriate prescribing leading to poor clinical outcomes. Based on the published literature, a comprehensive HF-specific prescribing review tool is compiled to avoid medications that may cause HF or harm HF patients and to optimize the prescribing practice of HF guideline-directed medical therapies. Recommendations are made in line with the last versions of ESC guidelines, ESC position papers, scientific evidence, and experts' opinions.
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http://dx.doi.org/10.1093/ehjcvp/pvaa108DOI Listing
September 2020

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

J Diabetes Complications 2020 11 28;34(11):107692. Epub 2020 Jul 28.

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107692DOI Listing
November 2020

Serum Parathyroid Hormone Predicts Mortality in Coronary Angiography Patients with Type 2 Diabetes.

J Clin Endocrinol Metab 2020 11;105(11)

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.

Background: Elevated serum levels of parathyroid hormone (PTH), one of the main regulators of calcium homeostasis and vitamin D metabolism, have been proposed as predictors of mortality. The impact of type 2 diabetes mellitus (T2DM) on the putative association between PTH and mortality has not been investigated thus far.

Aim: The aim of our study was to investigate the impact of T2DM on the power of PTH to predict mortality risk.

Methods: Serum PTH levels were determined in 904 consecutive Caucasian patients referred to coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD), including 235 patients with T2DM. Prospectively, deaths were recorded over a mean follow-up period of 6.3 years.

Results: PTH at baseline did not differ significantly between patients with and without T2DM (P = .307). Cox regression analysis revealed that the serum PTH level strongly predicted all-cause mortality in patients with T2DM (hazard ratio [HR] = 2.35 [1.37-4.03]; P = .002), whereas PTH did not predict all-cause mortality in patients without T2DM (HR = 1.04 [0.81-1.32]; P = .766). The interaction term PTH × T2DM was significant (P = .006), indicating a significantly stronger impact of PTH on mortality risk in patients with T2DM than in individuals without diabetes. The impact of PTH on mortality risk in patients with T2DM remained significant after adjustment for glycated hemoglobin A1c, diabetes duration, classical cardiovascular risk factors, serum levels of vitamin D, and kidney function (HR = 2.10 [1.10-4.10]; P = .030).

Conclusion: We conclude that PTH is a significantly stronger predictor of all-cause mortality in patients with T2DM than in those without T2DM.
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http://dx.doi.org/10.1210/clinem/dgaa512DOI Listing
November 2020

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

Am J Cardiol 2020 08 16;129:5-9. Epub 2020 May 16.

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine I, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.

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.
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http://dx.doi.org/10.1016/j.amjcard.2020.05.006DOI Listing
August 2020

Development of a 3-Dimensional Prognostic Score for Patients With Symptomatic Peripheral Artery Disease: PAD Score.

Angiology 2020 08 28;71(7):658-665. Epub 2020 Apr 28.

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.

Peripheral artery disease (PAD) is a high-risk condition for cardiovascular (CV) events, but no specific prognosis assessment tool exists. We developed an individual risk score (PAD) based on the combined predictive value for mortality, including (1) age, (2) severity of PAD, and (3) extent of atherosclerosis. Patients (n = 1310) with symptomatic PAD were followed up for a mean of 50 ± 26 months. The cohort was randomly subdivided into a test and validation cohort. All-cause and CV mortality were prospectively analyzed for PAD score and in combination with classical risk factors. For the test and validation cohort (n = 655 each), all-cause and CV mortality were predicted ( < .001) by the PAD score. Additional inclusion of classical risk factors did not increase discrimination compared with PAD as "area under receiver-operating characteristic" curves were similar for both scores at any time point. Thus, the addition of the classical risk factors to PAD did not further improve the prognostic value. The PAD score provides a risk gradient of a 4.5-fold increase in all-cause and CV mortality. We developed a score for precise prediction of all-cause and CV mortality. The PAD score promises to allow for personalized goals in risk intervention.
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http://dx.doi.org/10.1177/0003319720920155DOI Listing
August 2020

Marked differences in prediabetes- and diabetes-associated comorbidities between men and women-Epidemiological results from a general population-based cohort aged 6-80 years-The LEAD (Lung, hEart, sociAl, boDy) study.

Eur J Clin Invest 2020 Mar 12;50(3):e13207. Epub 2020 Feb 12.

Department of Respiratory and Critical Care Medicine and Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria.

Background: Based on biological and behavioural diversity sex and gender may affect comorbidities associated with prediabetes and diabetes. Besides evaluating the prevalence of prediabetes and diabetes (using fasting plasma glucose and HbA1 levels), the primary aim of the study is to investigate sex and gender differences in the prevalence of comorbidities in subjects with prediabetes and diabetes and to identify possible risk factors associated with prediabetes and diabetes.

Design: This observational, population-based cohort study included 11.014 subjects aged 6-80 years. Examinations included blood samples, ankle-brachial index, ECG, dual-energy X-ray absorptiometry scan and an interviewer-administered questionnaire.

Results: Across all ages, prevalence of prediabetes was 20.2% (male 23.6%; female 17.1%), and 5.4% for diabetes (male 7.3%; female 3.7%). The prevalence of prediabetes ranged from 4.4% (6-<10 years) up to 40.4% (70+ years) in men and from 4.8% up to 42.3% in women. Comorbidity profile was markedly different between male and female, particularly in those with prediabetes: women more often suffered from arrhythmia, noncoronary artery disease, osteoporosis, increased systemic inflammatory biomarkers and depression, while men with prediabetes more often showed angina pectoris, myocardial infarction and media sclerosis.

Conclusions: The unexpected 4.6% prevalence of prediabetes in children aged 6-10 underscores the need for population-based studies across all ages and the onset of prevention of diabetes at a young age. Marked differences have been found in comorbidities as men with prediabetes and diabetes more often suffer from cardiovascular disease, while women more often show arrhythmia, noncoronary artery disease, increased systemic inflammatory biomarkers and depression.
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http://dx.doi.org/10.1111/eci.13207DOI Listing
March 2020
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