Healthy lifestyle over the life course: Population trends and individual changes over 30 years of the Doetinchem Cohort Study.

For five health-related lifestyle factors (physical activity, weight, smoking, sleep, and alcohol consumption) we describe both population trends and individual changes over a period of 30 years in the same adult population. Dichotomous indicators (healthy/unhealthy) of lifestyle were analyzed for 3,139 participants measured every 5 years in the Doetinchem Cohort Study (1987-2017). Population trends over 30 years in physical inactivity and "unhealthy" alcohol consumption were flat (i.e., stable); overweight and unhealthy sleep prevalence increased; smoking prevalence decreased. The proportion of the population being healthy on all five lifestyle factors declined from 17% in the round 1 to 10.8% in round 6. Underlying these trends a dynamic pattern of changes at the individual level was seen: sleep duration and physical activity level changed in almost half of the individuals; Body Mass Index (BMI) and alcohol consumption in one-third; smoking in one-fourth. Population trends don't give insight into change at the individual level. In order to be able to gauge the potential for change of health-related lifestyle, it is important to take changes at the individual level into account.

Aging-related trajectories of lung function in the general population-The Doetinchem Cohort Study.

The objective of this study was to explore trajectories of lung function decline with age in the general population, and to study the effect of sociodemographic and life style related risk factors, in particular smoking and BMI. For this purpose, we used data from the Doetinchem Cohort Study (DCS) of men and women, selected randomly from the general population and aged 20-59 years at inclusion in 1987-1991, and followed until the present. Participants in the DCS are assessed every five years. Spirometry has been performed as part of this assessment from 1994 onwards. Participants were included in this study if spirometric measurement of FEV1, which in this study was the main parameter of interest, was acceptable and reproducible on at least one measurement round, leading to the inclusion of 5727 individuals (3008 females). Statistical analysis revealed three typical trajectories. The majority of participants followed a trajectory that closely adhered to the Global Lung Initiative Reference values (94.9% of men and 96.4% of women). Two other trajectories showed a more pronounced decline. Smoking and the presence of respiratory complaints were the best predictors of a trajectory with stronger decline. A greater BMI over the follow-up period was associated with a more unfavorable FEV1 course both in men (ß = -0.027 (SD = 0.002); P < 0.001) and in women (ß = -0.008 (SD = 0.001); P < 0.001). Smokers at baseline who quit the habit during follow-up, showed smaller decline in FEV1 in comparison to persistent smokers, independent of BMI change (In men ß = -0.074 (SD = 0.020); P < 0.001. In women ß = -0.277 (SD = 0.068); P < 0.001). In conclusion, three typical trajectories of age-related FEV1 decline could be distinguished. Change in the lifestyle related risk factors, BMI and smoking, significantly impact aging-related decline of lung function. Identifying deviant trajectories may help in early recognition of those at risk of a diagnosis of lung disease later in life.

You Only Die Once: Accounting for Multi-Attributable Mortality Risks in Multi-Disease Models for Health-Economic Analyses.

Mortality rates in Markov models, as used in health economic studies, are often estimated from summary statistics that allow limited adjustment for confounders. If interventions are targeted at multiple diseases and/or risk factors, these mortality rates need to be combined in a single model. This requires them to be mutually adjusted to avoid 'double counting' of mortality. We present a mathematical modeling approach to describe the joint effect of mutually dependent risk factors and chronic diseases on mortality in a consistent manner. Most importantly, this approach explicitly allows the use of readily available external data sources. An additional advantage is that existing models can be smoothly expanded to encompass more diseases/risk factors. To illustrate the usefulness of this method and how it should be implemented, we present a health economic model that links risk factors for diseases to mortality from these diseases, and describe the causal chain running from these risk factors (e.g., obesity) through to the occurrence of disease (e.g., diabetes, CVD) and death. Our results suggest that these adjustment procedures may have a large impact on estimated mortality rates. An improper adjustment of the mortality rates could result in an underestimation of disease prevalence and, therefore, disease costs.

[Doubts about the new oral anticoagulants]. / Vraagtekens bij de nieuwe antistollingsmiddelen: alarmerend signaal over de introductie van NOAC's.

Recently, The British Medical Journal published three articles and an editorial on the RE-LY trial and the admission to the market of dabigatran. In these publications, concerns were raised regarding the data in this key trial and the registration process. Moreover, a lack of transparency was brought to light about the safety of unmonitored dabigatran use. The results of the RE-LY trial were important evidence for an advice of the Health Council of the Netherlands on the introduction of the new oral anticoagulants (NOACs) in the Netherlands, published in 2012. At present, the question arises whether dabigatran use requires monitoring and what the consequences are for the cost-effectiveness of NOACs.

Disease prevention: saving lives or reducing health care costs?

BACKGROUND: Disease prevention has been claimed to reduce health care costs. However, preventing lethal diseases increases life expectancy and, thereby, indirectly increases the demand for health care. Previous studies have argued that on balance preventing diseases that reduce longevity increases health care costs while preventing non-fatal diseases could lead to health care savings. The objective of this research is to investigate if disease prevention could result in both increased longevity and lower lifetime health care costs. METHODS: Mortality rates for Netherlands in 2009 were used to construct cause-deleted life tables. Data originating from the Dutch Costs of Illness study was incorporated in order to estimate lifetime health care costs in the absence of selected disease categories. We took into account that for most diseases health care expenditures are concentrated in the last year of life. RESULTS: Elimination of diseases that reduce life expectancy considerably increase lifetime health care costs. Exemplary are neoplasms that, when eliminated would increase both life expectancy and lifetime health care spending with roughly 5% for men and women. Costs savings are incurred when prevention has only a small effect on longevity such as in the case of mental and behavioural disorders. Diseases of the circulatory system stand out as their elimination would increase life expectancy while reducing health care spending. CONCLUSION: The stronger the negative impact of a disease on longevity, the higher health care costs would be after elimination. Successful treatment of fatal diseases leaves less room for longevity gains due to effective prevention but more room for health care savings.

Biochemical markers of aging for longitudinal studies in humans.

Much progress has been made in the past decades in unraveling the mechanisms that are responsible for aging. The discovery that particular gene mutations in experimental species such as yeast, flies, and nematodes are associated with longevity has led to many important insights into pathways that regulate aging processes. However, extrapolating laboratory findings in experimental species to knowledge that is valid for the complexity of human physiology remains a major challenge. Apart from the restricted experimental possibilities, studying aging in humans is further complicated by the development of various age-related diseases. The availability of a set of biomarkers that really reflect underlying aging processes would be of much value in disentangling age-associated pathology from specific aging mechanisms. In this review, we survey the literature to identify promising biochemical markers of aging, with a particular focus on using them in longitudinal studies of aging in humans that entail repeated measurements on easily obtainable material, such as blood samples. Our search strategy was a 2-pronged approach, one focused on general mechanisms of aging and one including studies on clinical biomarkers of age-related diseases.

Population trends and inequalities in incidence and short-term outcome of acute myocardial infarction between 1998 and 2007.

OBJECTIVE: We studied time trends in acute myocardial infarction (AMI) incidence, including out-of-hospital mortality proportions and hospitalized case-fatality rates. In addition, we compared AMI trends by age, gender and socioeconomic status. METHODS: We linked the national Dutch hospital discharge register with the cause of death register to identify first AMI in patients ≥ 35 years between 1998 and 2007. Events were categorized in three groups: 178,322 hospitalized non-fatal, 43,210 hospitalized fatal within 28 days, and 75,520 out-of-hospital fatal AMI events. Time trends were analyzed using Joinpoint and Poisson regression. RESULTS: Since 1998, age-standardized AMI incidence rates decreased from 620 to 380 per 100,000 in 2007 in men and from 323 to 210 per 100,000 in 2007 in women. Out-of-hospital mortality decreased from 24.3% of AMI in 1998 to 20.6% in 2007 in men and from 33.0% to 28.9% in women. Hospitalized case-fatality declined from 2003 onwards. The annual percentage change in incidence was larger in men than women (-4.9% vs. -4.2%, P<0.001). Furthermore, the decline in AMI incidence was smaller in young (35-54 years: -3.8%) and very old (≥ 85 years: -2.6%) men and women compared to middle-aged individuals (55-84 years: -5.3%, P<0.001). Smaller declines in AMI rates were observed in deprived socioeconomic quintiles Q5 and Q4 relative to the most affluent quintile Q1 (P=0.002 and P=0.015). CONCLUSIONS: Substantial improvements were observed in incidence, out-of-hospital mortality and short-term case-fatality after AMI in the Netherlands. Young and female groups tend to fall behind, and socioeconomic inequalities in AMI incidence persisted and have not narrowed.

Neighbourhood socioeconomic inequalities in incidence of acute myocardial infarction: a cohort study quantifying age- and gender-specific differences in relative and absolute terms.

BACKGROUND: Socioeconomic status has a profound effect on the risk of having a first acute myocardial infarction (AMI). Information on socioeconomic inequalities in AMI incidence across age-gender-groups is lacking. Our objective was to examine socioeconomic inequalities in the incidence of AMI considering both relative and absolute measures of risk differences, with a particular focus on age and gender. METHODS: We identified all patients with a first AMI from 1997 to 2007 through linked hospital discharge and death records covering the Dutch population. Relative risks (RR) of AMI incidence were estimated by mean equivalent household income at neighbourhood-level for strata of age and gender using Poisson regression models. Socioeconomic inequalities were also shown within the stratified age-gender groups by calculating the total number of events attributable to socioeconomic disadvantage. RESULTS: Between 1997 and 2007, 317,564 people had a first AMI. When comparing the most deprived socioeconomic quintile with the most affluent quintile, the overall RR for AMI was 1.34 (95 % confidence interval (CI): 1.32-1.36) in men and 1.44 (95 % CI: 1.42-1.47) in women. The socioeconomic gradient decreased with age. Relative socioeconomic inequalities were most apparent in men under 35 years and in women under 65 years. The largest number of events attributable to socioeconomic inequalities was found in men aged 45-74 years and in women aged 65-84 years. The total proportion of AMIs that was attributable to socioeconomic inequalities in the Dutch population of 1997 to 2007 was 14 % in men and 18 % in women. CONCLUSIONS: Neighbourhood socioeconomic inequalities were observed in AMI incidence in the Netherlands, but the magnitude across age-gender groups depended on whether inequality was expressed in relative or absolute terms. Relative socioeconomic inequalities were high in young persons and women, where the absolute burden of AMI was low. Absolute socioeconomic inequalities in AMI were highest in the age-gender groups of middle-aged men and elderly women, where the number of cases was largest.

The polypill in the primary prevention of cardiovascular disease: cost-effectiveness in the Dutch population.

Objectives The aim of the present study was to estimate the cost-effectiveness of the polypill in the primary prevention of cardiovascular disease. Design A health economic modelling study. Setting Primary healthcare in the Netherlands. Participants Simulated individuals from the general Dutch population, aged 45-75 years. Interventions Opportunistic screening followed by prescription of the polypill to eligible individuals. Eligibility was defined as having a minimum 10-year risk of cardiovascular death as assessed with the Systematic Coronary Risk Evaluation function of alternatively 5%, 7.5% or 10%. Different versions of the polypill were considered, depending on composition: (1) the Indian polycap, with three different types of blood pressure-lowering drugs, a statin and aspirin; (2) as (1) but without aspirin and (3) as (2) but with a double statin dose. In addition, a scenario of (targeted) separate antihypertensive and/or statin medication was simulated. Primary outcome measures Cases of acute myocardial infarction or stroke prevented, quality-adjusted life years (QALYs) gained and the costs per QALY gained. All interventions were compared with usual care. Results All scenarios were cost-effective with an incremental cost-effectiveness ratio between €7900 and 12 300 per QALY compared with usual care. Most health gains were achieved with the polypill without aspirin and containing a double dose of statins. With a 10-year risk of 7.5% as the threshold, this pill would prevent approximately 3.5% of all cardiovascular events. Conclusions Opportunistic screening based on global cardiovascular risk assessment followed by polypill prescription to those with increased risk offers a cost-effective strategy. Most health gain is achieved by the polypill without aspirin and a double statin dose.

Co-occurrence of diabetes, myocardial infarction, stroke, and cancer: quantifying age patterns in the Dutch population using health survey data.

BACKGROUND: The high prevalence of chronic diseases in Western countries implies that the presence of multiple chronic diseases within one person is common. Especially at older ages, when the likelihood of having a chronic disease increases, the co-occurrence of distinct diseases will be encountered more frequently. The aim of this study was to estimate the age-specific prevalence of multimorbidity in the general population. In particular, we investigate to what extent specific pairs of diseases cluster within people and how this deviates from what is to be expected under the assumption of the independent occurrence of diseases (i.e., sheer coincidence). METHODS: We used data from a Dutch health survey to estimate the prevalence of pairs of chronic diseases specified by age. Diseases we focused on were diabetes, myocardial infarction, stroke, and cancer. Multinomial P-splines were fitted to the data to model the relation between age and disease status (single versus two diseases). To assess to what extent co-occurrence cannot be explained by independent occurrence, we estimated observed/expected co-occurrence ratios using predictions of the fitted regression models. RESULTS: Prevalence increased with age for all disease pairs. For all disease pairs, prevalence at most ages was much higher than is to be expected on the basis of coincidence. Observed/expected ratios of disease combinations decreased with age. CONCLUSION: Common chronic diseases co-occur in one individual more frequently than is due to chance. In monitoring the occurrence of diseases among the population at large, such multimorbidity is insufficiently taken into account.

Estimating and comparing incidence and prevalence of chronic diseases by combining GP registry data: the role of uncertainty.

BACKGROUND: Estimates of disease incidence and prevalence are core indicators of public health. The manner in which these indicators stand out against each other provide guidance as to which diseases are most common and what health problems deserve priority. Our aim was to investigate how routinely collected data from different general practitioner registration networks (GPRNs) can be combined to estimate incidence and prevalence of chronic diseases and to explore the role of uncertainty when comparing diseases. METHODS: Incidence and prevalence counts, specified by gender and age, of 18 chronic diseases from 5 GPRNs in the Netherlands from the year 2007 were used as input. Generalized linear mixed models were fitted with the GPRN identifier acting as random intercept, and age and gender as explanatory variables. Using predictions of the regression models we estimated the incidence and prevalence for 18 chronic diseases and calculated a stochastic ranking of diseases in terms of incidence and prevalence per 1,000. RESULTS: Incidence was highest for coronary heart disease and prevalence was highest for diabetes if we looked at the point estimates. The between GPRN variance in general was higher for incidence than for prevalence. Since uncertainty intervals were wide for some diseases and overlapped, the ranking of diseases was subject to uncertainty. For incidence shifts in rank of up to twelve positions were observed. For prevalence, most diseases shifted maximally three or four places in rank. CONCLUSION: Estimates of incidence and prevalence can be obtained by combining data from GPRNs. Uncertainty in the estimates of absolute figures may lead to different rankings of diseases and, hence, should be taken into consideration when comparing disease incidences and prevalences.

To die with or from heart failure: a difference that counts: is heart failure underrepresented in national mortality statistics?

AIMS: Mortality attributed to a disease is an important public health measure of the 'burden' of that disease. A discrepancy has been noted between the high mortality rates associated with heart failure (HF) and the share of deaths ascribed to HF in official mortality statistics. It was our main aim to estimate excess mortality associated with HF and use the estimates to better understand the burden of HF. METHODS AND RESULTS: Excess mortality was defined as the difference in mortality rates between individuals with and those without HF. An epidemiological model was formulated that allowed deriving age-specific excess mortality rates in HF patients from HF incidence and prevalence. Incidence and prevalence were estimated from yearly collected cross-sectional data from four nationally representative General Practice registries in the Netherlands. The year 2007 was chosen as a reference. Next, excess mortality rates were used to calculate numbers of deaths among HF patients and compare the figures with national cause-of-death statistics. The latter were found to be more than three times smaller than the former (roughly 6000 vs. 21 000). Further, by applying HF prevalence and mortality rates to a life table of the Dutch population, average numbers of life years lost due to HF were calculated to be 6.9 years. CONCLUSION: National mortality statistics strongly underestimate the number of deaths associated with HF. Moreover, the high mortality rate in HF patients amounts to a remarkably large number of life years lost given the advanced age of disease onset.

Rendering hospital budgets volume based and open ended to reduce waiting lists: does it work?

In the past decades fixed budgets for hospitals were replaced by reimbursement based on outputs in several countries in order to bring down waiting lists. This was also the case in the Netherlands where fixed global budgets were replaced by budgets that are to a large extent volume based and in practice open-ended. The objective of this study was to examine the effectiveness of this Dutch policy measure, which was implemented in 2001. We carried out a statistical analysis and interpretation of trends in Dutch hospital admission rates. We observed a significant turn in the development of in-patient admission rates after the abolition of budget caps in 2001: decreasing admission rates turned into an internationally exceptional increase of more than 3% per year. Day care admissions had already been rising explosively for two decades, but the pace increased after 2001. The increase in the number of admissions includes a broad range of patient categories that were not in the first place associated with long waiting times. The growth was attributable for a large part to admissions for observation of the patient and the evaluation of symptoms, not resulting in a definite medical diagnosis. We considered several factors, other than the availability of more resources, to explain the growth: the ageing of the population, making up for waiting list arrears, ditto for "under consumption" of unplanned care and, as to the growth of day care, substitution for inpatient care. However, these factors were all found to fall short as an explanation. Although waiting times have dropped since the change in the budget system, they continue to be long for several procedures. Our study indicates that making available more resources to admit patients, or otherwise an increase in hospital activity, do not in itself lead to equilibrium between demand and supply because the volume and composition of demand are partly induced by supply. We conclude that abolishing budget caps to solve waiting list problems is not efficient. Instead of a generic measure, a more focused approach is necessary. We suggest ingredients for such an approach.

Lipid-lowering treatment for all could substantially reduce the burden of macrovascular complications of diabetes patients in the Netherlands.

BACKGROUND: We aimed to quantify the potential health benefits of increased use of lipid-lowering treatment (LLT), according to current guidelines, for the Dutch diabetes population. DESIGN: Simulation study. METHODS: We compared the long-term health outcomes for a scenario in which all diabetes patients received LLT to those in a 'current practice' scenario, in which 28% received LLT. The model reflected the Dutch diabetes population 40-80 years of age, in 2003. Sensitivity analyses were performed, using more conservative assumptions. RESULTS: Over the lifetime, LLT for all diabetes patients reduced the expected cumulative incidences of coronary heart disease (CHD) and stroke by, respectively, 6 and 9%. Average life expectancy of Dutch diabetes patients would increase by 0.33 years, ranging from 0.14 years for patients aged 70-79 years, to 0.84 years for patients aged 40-49 years at the start of the simulation. Life-long treatment for patients aged 50-59 contributed most to the life years gained (55,000 out of 146,000). With reduced effectiveness of LLT and fewer patients starting LLT, the cumulative incidences of both CHD and stroke would decrease by approximately 2%. The number needed to treat to prevent one incident case of cardiovascular disease over lifetime was 20 for CHD and 44 for stroke. CONCLUSION: This simulation study shows that increased use of LLT can substantially reduce the expected future burden of CHD and stroke in the Dutch diabetes population.

Cost-effectiveness of a low-calorie diet and orlistat for obese persons: modeling long-term health gains through prevention of obesity-related chronic diseases.

OBJECTIVE: Our study estimated the cost-effectiveness of pharmacologic treatment of obesity in combination with a low-calorie diet in The Netherlands. METHODS: Costs and effects of a low-calorie diet-only intervention and of a low-calorie diet in combination with 1 year of orlistat were compared to no treatment. The RIVM Chronic Disease Model was used to project the differences in quality adjusted life years (QALYs) and lifetime health-care costs because of the effects of the interventions on body mass index (BMI) status. This was done by linking BMI status to the occurrence of obesity-related diseases and by relating quality of life to disease status. Probabilistic sensitivity analysis was employed to study the effect of uncertainty in the model parameters. In univariate sensitivity analysis, we assessed how sensitive the results were to several key assumptions. RESULTS: Incremental costs per QALY gained were Euro 17,900 for the low-calorie diet-only intervention compared to no intervention and Euro 58,800 for the low-calorie diet + orlistat compared to the low-calorie diet only. Assuming a direct relation between BMI and quality of life, these ratios decreased to Euro 6000 per QALY gained and Euro 24,100 per QALY gained. Costs per QALY gained were also sensitive to assumptions about long-term weight loss maintenance. CONCLUSIONS: Cost-effectiveness ratios of interventions aiming at weight reduction depend strongly on assumptions regarding the relation between BMI and quality of life. We recommend that a low-calorie diet should be the first option for policymakers in combating obesity.

Lifetime medical costs of obesity: prevention no cure for increasing health expenditure.

BACKGROUND: Obesity is a major cause of morbidity and mortality and is associated with high medical expenditures. It has been suggested that obesity prevention could result in cost savings. The objective of this study was to estimate the annual and lifetime medical costs attributable to obesity, to compare those to similar costs attributable to smoking, and to discuss the implications for prevention. METHODS AND FINDINGS: With a simulation model, lifetime health-care costs were estimated for a cohort of obese people aged 20 y at baseline. To assess the impact of obesity, comparisons were made with similar cohorts of smokers and "healthy-living" persons (defined as nonsmokers with a body mass index between 18.5 and 25). Except for relative risk values, all input parameters of the simulation model were based on data from The Netherlands. In sensitivity analyses the effects of epidemiologic parameters and cost definitions were assessed. Until age 56 y, annual health expenditure was highest for obese people. At older ages, smokers incurred higher costs. Because of differences in life expectancy, however, lifetime health expenditure was highest among healthy-living people and lowest for smokers. Obese individuals held an intermediate position. Alternative values of epidemiologic parameters and cost definitions did not alter these conclusions. CONCLUSIONS: Although effective obesity prevention leads to a decrease in costs of obesity-related diseases, this decrease is offset by cost increases due to diseases unrelated to obesity in life-years gained. Obesity prevention may be an important and cost-effective way of improving public health, but it is not a cure for increasing health expenditures.

Smoking and its effects on mortality in adults with congenital heart disease.

AIMS: To describe smoking habits in adults with congenital heart disease (ACHD) and to assess the relationship between smoking exposure and cardiovascular mortality. METHODS: Data on smoking history and cardiovascular mortality were extracted from the Euro Heart Survey on adult congenital heart disease - a retrospective cohort study, that included patients diagnosed with 1 of 8 subgroups of ACHD (Atrial Septal Defects, Ventricular Septal Defects, Marfan Syndrome, Aortic Coarctation, Tetralogy of Fallot (ToF), Transposition of the Great Arteries (TGA), Fontan circulation, and Cyanotic disease). RESULTS: Complete data of 3375 ACHD patients (median age 28 years) were available for analysis. At inclusion, 9.3% (n=314) were current smokers and 4.2% (n=142) of the patients had smoked in the past. During a median follow-up of 5.1 years, 101 patients (3%) died. In the majority of cases the cause of death was cardiovascular (n=81; 80%). Kaplan-Meier and Cox survival analysis for each of the defects separately showed a significantly increased age and sex-adjusted cardiovascular mortality associated with smoking exposure in TGA patients (Hazard ratio 4.2 (95% CI 1.0-16.8); P=0.044). Also in ToF mortality was higher amongst smokers, though not significantly (HR 3.4 (95% CI 0.6-18.5); P=0.15). In the remaining defects no relationship between smoking and cardiovascular mortality was observed. CONCLUSION: The prevalence of smoking amongst ACHD patients is relatively low. Smoking exposure is associated with increased cardiovascular mortality in patients with TGA. Prospective long-term follow-up studies are necessary.

Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease.

AIM: To investigate the role of pulmonary arterial hypertension (PAH) in adult patients born with a cardiac septal defect, by assessing its prevalence and its relation with patient characteristics and outcome. METHODS AND RESULTS: From the database of the Euro Heart Survey on adult congenital heart disease (a retrospective cohort study with a 5-year follow-up), the relevant data on all 1877 patients with an atrial septal defect (ASD), a ventricular septal defect (VSD), or a cyanotic defect were analysed. Most patients (83%) attended a specialised centre. There were 896 patients with an ASD (377 closed, 504 open without and 15 with Eisenmenger's syndrome), 710 with a VSD (275, 352 and 83, respectively), 133 with Eisenmenger's syndrome owing to another defect and 138 remaining patients with cyanosis. PAH was present in 531 (28%) patients, or in 34% of patients with an open ASD and 28% of patients with an open VSD, and 12% and 13% of patients with a closed defect, respectively. Mortality was highest in patients with Eisenmenger's syndrome (20.6%). In case of an open defect, PAH entailed an eightfold increased probability of functional limitations (New York Heart Association class >1), with a further sixfold increase when Eisenmenger's syndrome was present. Also, in patients with persisting PAH despite defect closure, functional limitations were more common. In patients with ASD, the prevalence of right ventricular dysfunction increased with systolic pulmonary artery pressure (OR = 1.073 per mm Hg; p<0.001). Major bleeding events were more prevalent in patients with cyanosis with than without Eisenmenger's syndrome (17% vs 3%; p<0.001). CONCLUSION: In this selected population of adults with congenital heart disease, PAH was common and predisposed to more symptoms and further clinical deterioration, even among patients with previous defect closure and patients who had not developed Eisenmenger's physiology.

Aortic root growth in men and women with the Marfan's syndrome.

The leading cause of premature death in patients with Marfan's syndrome (MS) is type A aortic dissection or rupture due to progressive aortic root dilation. The aim of this study was to analyze aortic root growth in 113 men and 108 women with MS. All patients were prospectively followed with serial echocardiograms of the native aortic root. At baseline, women had on average a 5-mm smaller aortic root diameter adjusted for age than men. Average aortic root growth was 0.42 mm/year (SE 0.05) in men and 0.38 mm/year (SE 0.04) in women. On the basis of aortic root growth rates, the men and women could be divided into 2 normally distributed subgroups: fast and slow growers. Approximately 1 in 7 men (1.5 mm/year, SE 0.5) and approximately 1 in 9 women (1.8 mm/year, SE 0.3) had fast-growing aortic root diameters. Significantly more type A dissections (25% vs 4%, p <0.001) were observed in fast growers than in slow growers; this was found in men and women. Type A dissections were observed in 4 men and 9 women. By reducing the cut-off value by 5 mm for elective aortic root replacement in women, type A dissections could have been prevented in 3 women. In conclusion, guidelines should take gender differences into account, and therefore, the investigators propose reducing the threshold for elective aortic root replacement in women with MS by 5 mm.