The impact of type 2 diabetes and Microalbuminuria on future cardiovascular events in patients with clinically manifest vascular disease from the Second Manifestations of ARTerial Disease (SMART) study

Aims Type 2 diabetes mellitus and microalbuminuria are important risk factors for cardiovascular disease (CVD). Whether these two complications are important and independent risk factors for future CVD events in a high-risk population with clinically manifest vascular disease is unknown. The objectives of this study were to examine the impact of Type 2 diabetes and microalbuminuria on future CVD events. Methods Patients with clinically manifest vascular disease (coronary, cerebral and peripheral vascular disease) from the Second Manifestation of Arterial disease study were followed up for 4 years. Data obtained from 1996–2006 were analysed. At baseline, there were 804 patients with Type 2 diabetes mellitus (mean age 60 years) and 2983 patients without. Incident CVD (n = 458) was defined as hospital-verified myocardial infarction, stroke, vascular death and the composite of these vascular events. Results Both Type 2 diabetes [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.16, 1.75] and microalbuminuria (HR 1.86, 95% CI 1.49, 2.33) increased the risk of new cardiovascular events in univariate analyses. From multivariable models, presence of diabetes remained significantly and independently related to incident CVD (HR 1.42, 95% CI 1.11, 1.80). Presence of microalbuminuria also remained significantly independently related to incident CVD (HR 1.38, 95% CI 1.07, 1.77). In diabetes-stratified analyses, the effect of microalbuminuria on CVD risk was observed only in patients with diabetes. In microalbuminuria-stratified analyses, the significant and independent effect of diabetes on CVD risk was shown only in the non-microalbuminuric group. Conclusions In this high-risk population, both microalbuminuria and Type 2 diabetes are important and independent risk factors for future CV

Risk factors for lobar and non-lobar intracerebral hemorrhage in patients with vascular disease

Introduction Lobar and non-lobar non-traumatic intracerebral hemorrhage (ICH) are presumably caused by different types of small vessel diseases. The aim of this study was to assess risk factors for ICH according to location. Methods In two large prospective studies, SMART (n = 9088) and ESPRIT (n = 2625), including patients with manifest cardiovascular, cerebrovascular or peripheral artery disease or with vascular risk factors, we investigated potential risk factors for ICH during follow-up according to lobar or non-lobar location by Cox proportional hazards analyses. Results During 65,156 patient years of follow up 19 patients had lobar ICH (incidence rate 29, 95% CI 19-42 per 100,000 person-years) and 24 non-lobar ICH (incidence rate 37, 95% CI 26-51 per 100,000 person-years). Age significantly increased the risk of lobar ICH (HR per 10 years increase 1.90; 95% CI 1.17-3.10) in the multivariable analysis, but not of non-lobar hemorrhage. Anticoagulant medication (HR 3.49; 95% CI 1.20-10.2) and male sex (HR 3.79; 95% CI 1.13-12.8) increased the risk of non-lobar but not lobar ICH. Conclusion This study shows an elevated risk of future ICH in patients with manifestations of, or risk factors for, cardiovascular, cerebrovascular or peripheral artery disease. Our data suggest that risk factors for ICH vary according to location, supporting the hypothesis of a differential pathophysiology of lobar and non-lobar ICH

Smoking cessation and risk of recurrent cardiovascular events and mortality after a first manifestation of arterial disease

Aims To quantify the relation between smoking cessation after a first cardiovascular (CV) event and risk of recurrent CV events and mortality. Methods Data were available from 4,673 patients aged 61 ± 8.7 years, with a recent (≤1 year) first manifestation of arterial disease participating in the SMART-cohort. Cox models were used to quantify the relation between smoking status and risk of recurrent major atherosclerotic cardiovascular events (MACE including stroke, MI and vascular mortality) and mortality. In addition, survival according to smoking status was plotted, taking competing risk of non-vascular mortality into account. Results A third of the smokers stopped after their first CV event. During a median of 7.4 (3.7–10.8) years of follow-up, 794 patients died and 692 MACE occurred. Compared to patients who continued to smoke, patients who quit had a lower risk of recurrent MACE (adjusted HR 0.66, 95% CI 0.49–0.88) and all-cause mortality (adjusted HR 0.63, 95% CI 0.48–0.82). Patients who reported smoking cessation on average lived 5 life years longer and recurrent MACE occurred 10 years later. In patients with a first CV event N70 years, cessation of smoking had improved survival which on average was comparable to former or never smokers. Conclusions Irrespective of age at first CV event, cessation of smoking after a first CV event is related to a substantial lower risk of recurrent vascular events and all-cause mortality. Since smoking cessation is more effective in reducing CV risk than any pharmaceutical treatment of major risk factors, it should be a key objective for patients with vascular disease. (A

The challenge of choosing in cardiovascular risk management

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options.Cardiolog

No additional prognostic value of genetic information in the prediction of vascular events after cerebral ischemia of arterial origin

Background: Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information. Methods and Results: We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke. Conclusions: We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87–0.94), with an additional relative risk for CVD of 0.92 (0.87–0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75–0.93), 0.76 (0.67–0.85), 0.69 (0.59–0.79), or 0.63 (0.52–0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials

Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer

Introduction Cardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for patients with pre-existing CVD risk factors. Early identification of patients at increased CVD risk may allow switching to less cardiotoxic treatments, active surveillance or treatment of CVD risk factors. One of the strongest independent CVD risk factors is the presence and extent of coronary artery calcifications (CAC). In clinical practice, CAC are generally quantified on ECGtriggered cardiac CT scans. Patients with breast cancer treated with radiotherapy routinely undergo radiotherapy planning CT scans of the chest, and those scans could provide the opportunity to routinely assess CAC before a potentially cardiotoxic treatment. The Bragatston study aims to investigate the association between calcifications in the coronary arteries, aorta and heart valves (hereinafter called ‘cardiovascular calcifications’) measured automatically on planning CT scans of patients with breast cancer and CVD risk. Methods and analysis In a first step, we will optimise and validate a deep learning algorithm for automated quantification of cardiovascular calcifications on planning CT scans of patients with breast cancer. Then, in a multicentre cohort study (University Medical Center Utrecht, Utrecht, Erasmus MC Cancer Institute, Rotterdam and Radboudumc, Nijmegen, The Netherlands), the association between cardiovascular calcifications measured on planning CT scans of patients with breast cancer (n≈16 000) and incident (non-)fatal CVD events will be evaluated. To assess the added predictive value of these calcifications over traditional CVD risk factors and treatment characteristics, a case-cohort analysis will be performed among all cohort members diagnosed with a CVD event during follow-up (n≈200) and a random sample of the baseline cohort (n≈600). Ethics and dissemination The Institutional Review Boards of the participating hospitals decided that the Medical R

SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions

Aims The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged over 70 years in four geographical risk regions.Methods and results Sex-specific competing risk-adjusted models for estimating CVD risk (CVD mortality, myocardial infarction, or stroke) were derived in individuals aged over 65 without pre-existing atherosclerotic CVD from the Cohort of Norway (28 503 individuals, 10 089 CVD events). Models included age, smoking status, diabetes, systolic blood pressure, and total- and high-density lipoprotein cholesterol. Four geographical risk regions were defined based on country-specific CVD mortality rates. Models were recalibrated to each region using region-specific estimated CVD incidence rates and risk factor distributions. For external validation, we analysed data from 6 additional study populations {338 615 individuals, 33 219 CVD validation cohorts, C-indices ranged between 0.63 [95% confidence interval (CI) 0.61-0.65] and 0.67 (0.64-0.69)}. Regional calibration of expected-vs.-observed risks was satisfactory. For given risk factor profiles, there was substantial variation across the four risk regions in the estimated 10-year CVD event risk.Conclusions The competing risk-adjusted SCORE2-OP model was derived, recalibrated, and externally validated to estimate 5- and 10-year CVD risk in older adults (aged 70 years or older) in four geographical risk regions. These models can be used for communicating the risk of CVD and potential benefit from risk factor treatment and may facilitate shared decision-making between clinicians and patients in CVD risk management in older persons.Cardiolog

Communicerende vaten

Een discussie tussen 2 wetenschappers ongeveer 450 jaar geleden verliep mogelijk als volgt: “Wat opmerkelijk! Als 2 emmers gevuld met water onderaan met een slangetje aan elkaar worden verbonden dan wordt het waterpeil in beide emmers gelijk. Ook als de ene emmer veel meer water bevat dan de andere of als de ene emmer veel groter is dan de andere.” “Interessante observatie collega, maar wat nog interessanter is, is als je een rietje in de zee steekt, dan vult het zich met water. Als je vervolgens op het rietje blaast dan daalt het waterpeil in het rietje. Daarmee moet dan wel het waterpeil in de zee stijgen. Weliswaar maar een heel klein beetje, maar het stijgt. Je bent dus in staat door te blazen op een rietje het waterpeil in de hele zee te laten stijgen. Ongelooflijk.” Dames en heren, in deze discussie zit de essentie van wetenschap. Verwondering, observatie en een diepe drang om iets te willen begrijpen en te willen weten, gedreven door nieuwsgierigheid en in het vertrouwen nieuwe kennis en inzichten te verwerven. De dialoog zou overigens ook een hedendaags gesprek geweest kunnen zijn tussen een meisje van 11 jaar en een jongen van 13 jaar oud

Adipose tissue dysfunction and hypertriglyceridemia: mechanisms and management

Development and application of statistical models for medical scientific researc