Jaap W. Deckers

Right bundle branch block: prevalence, risk factors, and outcome in the general population: results from the Copenhagen City Heart Study

AIMSnTo determine the prevalence, predictors of newly acquired, and the prognostic value of right bundle branch block (RBBB) and incomplete RBBB (IRBBB) on a resting 12-lead electrocardiogram in men and women from the general population.nnnMETHODS AND RESULTSnWe followed 18 441 participants included in the Copenhagen City Heart Study examined in 1976-2003 free from previous myocardial infarction (MI), chronic heart failure, and left bundle branch block through registry linkage until 2009 for all-cause mortality and cardiovascular outcomes. The prevalence of RBBB/IRBBB was higher in men (1.4%/4.7% in men vs. 0.5%/2.3% in women, P < 0.001). Significant predictors of newly acquired RBBB were male gender, increasing age, high systolic blood pressure, and presence of IRBBB, whereas predictors of newly acquired IRBBB were male gender, increasing age, and low BMI. Right bundle branch block was associated with significantly increased all-cause and cardiovascular mortality in both genders with age-adjusted hazard ratios (HR) of 1.31 [95% confidence interval (CI), 1.11-1.54] and 1.87 (95% CI, 1.48-2.36) in the gender pooled analysis with little attenuation after multiple adjustment. Right bundle branch block was associated with increased risk of MI with an HR of 1.67 (95% CI, 1.16-2.42) and pacemaker insertion with an HR of 2.17 (95% CI, 1.22-3.86), but not with chronic heart failure (HR 1.37; 95% CI, 0.96-1.94), atrial fibrillation (HR 1.10; 95% CI, 0.73-1.67), or chronic obstructive pulmonary disease (HR 0.99; 95% CI, 0.60-1.62). The presence of IRBBB was not associated with any adverse outcome.nnnCONCLUSIONnIn this cohort study, RBBB and IRBBB were two to three times more common among men than women. Right bundle branch block was associated with increased cardiovascular risk and all-cause mortality, whereas IRBBB was not. Contrary to common perception, RBBB in asymptomatic individuals should alert clinicians to cardiovascular risk.

Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients

ADAMTS13 may play a role in arterial thrombosis by cleaving the highly active and thrombogenic ultralarge Von Willebrand Factor (VWF) multimers into less active VWF multimers. The aim was to investigate the relationship between plasma levels of ADAMTS13, VWF and genetic variation in the ADAMTS13 gene with cardiovascular disease. We performed a case-control study in 374 patients with a first-ever arterial thrombosis before the age of 45 years in males and 55 years in women. We included 218 patients with coronary heart disease (CHD), 109 patients with ischemic stroke (IS) and 47 patients with peripheral arterial disease (PAD) and 332 healthy population-based controls. ADAMTS13 and VWF levels were measured 1-3 months after the event. ADAMTS13 levels were associated with cardiovascular disease (OR antigen 5.1 (95% CI 3.1-8.5, p<0.001) and OR activity 4.4 (95% CI 2.5-7.5, p<0.001), in the lowest quartiles). VWF levels were associated with cardiovascular disease (OR antigen 2.1 (95% CI 1.3-3.3, p=0.001) and OR activity 2.0 (95% CI 1.3-3.1, p=0.003), in the highest quartile). Patients with combined low ADAMTS13 levels and high VWF levels had an odds ratio of 7.7 (95% CI 3.3-17.7) (p for trend <0.0001). No association was found between genetic variation in the ADAMTS13 gene with levels of ADAMTS13 or with risk of cardiovascular disease. In conclusion, levels of ADAMTS13 and VWF are strongly associated with the risk of cardiovascular disease.

The role of thrombin activatable fibrinolysis inhibitor in arterial thrombosis at a young age: the ATTAC study.

Summary.u2002 Background and objectives:u2002Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and may therefore contribute to the pathophysiology of arterial thrombosis. The aim of the present study was to elucidate the pathogenetic role of TAFI levels and genotypes in young patients with arterial thrombosis. Patients and methods:u2002In a case–control study, 327 young patients with a recent first‐ever event of coronary heart disease (CHD subgroup) or cerebrovascular disease (ischemic stroke subgroup) and 332 healthy young controls were included. TAFI levels [intact TAFI, activation peptide (TAFI‐AP) and (in)activated TAFI (TAFIa(i)] and TAFI activity were measured and genetic variations in the TAFI gene (−438G/A, 505G/A and 1040C/T) were determined. Results:u2002In the total group of patients, TAFIa(i) levels were higher (145.1u2003±u200337.5%) than in controls (137.5u2003±u200331.3%, Pu2003=u20030.02). Plasma levels of intact TAFI, TAFI‐AP and TAFI activity were similar in patients and controls. In the CHD subgroup (nu2003=u2003218), intact TAFI levels were higher (109.4u2003±u200323.0%) than in controls (102.8u2003±u200320.7%, Pu2003=u20030.02). In 325Ile/Ile homozygotes, lower TAFI levels and a decreased risk of arterial thrombosis were observed (OR 0.58, 95% CI 0.34–0.99) compared with patients with the common 325Thr/Thr genotype. This association was most evident in CHD patients (OR 0.48, 95% CI 0.26–0.90). Haplotype analyses supported a role for the Thr325Ile polymorphism. Conclusions:u2002TAFIa(i) levels were higher in patients with cardiovascular disease. Furthermore, the TAFI 325Thr/Ile polymorphism was associated with lower TAFI levels and with the risk of cardiovascular disease in young patients, especially in CHD.

Prognostic markers in young patients with premature coronary heart disease

OBJECTIVESnTo evaluate the survival and prognostic implications of cardiovascular, inflammatory and prothrombotic risk factors in young patients with premature coronary heart disease (CHD).nnnMETHODSnFollow-up data were obtained from 353 young patients with a first cardiac event (men ≤45 years and women ≤55 years). Baseline characteristics on traditional risk factors were collected at the time of the first event, and plasma levels of C-reactive protein (CRP), von Willebrand Factor (VWF), and fibrinogen were measured one to three months after the first event to exclude an acute phase response. We performed age and sex adjusted Cox regression analyses to assess the relationship between these factors and recurrent events with three different endpoints: all cause mortality, recurrent cardiac event (myocardial infarction or revascularisation procedure), and any recurrent event (cardiac event, cerebrovascular event or all cause mortality).nnnRESULTSnDuring a total follow-up time of 1483 person years (mean 4.2 years), 11 patients died (3%), 42 patients had a recurrent cardiac event (12%), and 53 patients had any recurrent event (15%). CRP was associated with an increased risk of any recurrent event (HR 1.28[95% CI = 1.02-1.59] per unit increase in lnCRP). Also, both CRP (5.00[1.04-24.04]) and fibrinogen (5.04[1.05-24.23]) were associated with all cause mortality when levels were above the 50th percentile.nnnCONCLUSIONSnFifteen percent of young patients with a first cardiac event have a recurrent event or die within a median follow-up of 4.2 years. In these young patients we have shown that, independently of cardiovascular risk factors, high CRP levels contribute to the risk of recurrent events, including all cause mortality, and high fibrinogen levels are associated with all cause mortality.

Insight into ACE inhibition in the prevention of cardiac events in stable coronary artery disease: The EUROPA trial

The European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) investigated the effect of angiotensin-converting enzyme inhibition on the prevention of cardiac events in patients with stable coronary artery disease (CAD) without apparent heart failure. Perindopril 8 mg/day significantly reduced a composite outcome of cardiovascular death, nonfatal myocardial infarction or resuscitated cardiac arrest by 20% compared with placebo, in addition to standard preventive therapies. This review describes the substudies and subpopulation analyses carried out within the EUROPA population, concluding that the benefits of perindopril extend to all stable CAD patients, even revascularized patients or those with preserved left ventricular function. Data on the pathophysiological mechanisms underlying CAD indicate direct vascular protection with perindopril. This helps explain why perindopril is beneficial in preventing cardiac events in stable CAD patients.

Intensive LDL lowering therapy for prevention of recurrent cardiovascular events: a word of caution

Physicians visiting the European Society of Cardiology (ESC) congress in London could not miss the extensive marketing of new low-density lipoprotein (LDL)-lowering therapies with ezetimibe and the PCSK-9 inhibitors. However, we think and will argue that a word of caution on their use in clinical practice is appropriate.nnThe European guidelines on cardiovascular disease prevention and management of stable coronary artery disease recommend a spectrum of measures to limit the risk of a first or recurrent coronary event, including abstinence from smoking, balanced nutrition, moderate exercise as well as drugs to control blood pressure, lipids and glucose levels.1,2 Specific targets are mentioned for blood pressure (130–139/80–85 mmHg) and LDL-cholesterol (1.8–3.0 mmol/L). However, these targets for LDL-cholesterol—based on the observations that lower LDL levels are associated with ever-lower risk for cardiovascular events—are quite arbitrary. In clinical practice, these targets are often not reached, in spite of intensive medical therapy.3,4 For instance, in the EUROASPIRE-IV survey, 64% of males and 78% of females had LDL levels higher than 2.0 mmol/L.3 Furthermore, 18% of these patients continued smoking after an acute coronary event or revascularization procedure, while 42% had an elevated blood pressure.nnThe usefulness of specific targets for LDL cholesterol levels has been questioned and has been abandoned in recent American guidelines.5 Nevertheless, European opinion leaders continue to emphasize the value of targets to improve adherence to therapy and to consider additional therapy, such as combination of statin and ezetimibe, in a small group of very high-risk patients .6 Such targeting is supported by the recently published results of IMPROVE-IT7 as will be discussed below. Furthermore, we …