Decreased endothelial function and increased subclinical heart failure in women several years after pre-eclampsia.

OBJECTIVES: Pre-eclampsia (PE) is associated with both postpartum endothelial dysfunction and asymptomatic structural heart alterations consistent with heart failure Stage B (HF-B). In this study, we assessed the relationship between endothelial function, measured by flow-mediated dilation (FMD), and HF-B in women with a history of PE. METHODS: This was an observational study in which 67 formerly pre-eclamptic women (≥ 4 years postpartum) and 37 healthy parous controls were assessed ultrasonographically for cardiac function and geometry, as well as for endothelial function by means of brachial artery FMD. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m2 ), concentric remodeling (relative wall thickness > 0.42 and LVMi ≤ 95 g/m2 ), mild systolic dysfunction (left ventricular ejection fraction > 40% and < 55%) or asymptomatic valvular disease. Cardiovascular and metabolic syndrome variables were compared between women with history of PE and controls, as well as between those in the formerly pre-eclamptic group who had HF Stage A, HF-B or no HF. Logistic regression analysis was performed to assess the associations of FMD with PE, metabolic syndrome risk factors and obstetric parameters. RESULTS: The prevalence of HF-B amongst formerly pre-eclamptic women was three-fold higher than that observed for controls (25% vs 8%, P < 0.05), while FMD was lower in formerly pre-eclamptic women compared with controls (6.12% vs 8.22%, P < 0.01); history of PE remained associated independently with lower FMD after adjusting for metabolic syndrome risk factors and obstetric parameters (ß, -1.88; 95% CI, -3.59 to -0.18). However, HF-B did not relate to low FMD in formerly pre-eclamptic women. CONCLUSIONS: Years after pregnancy, formerly pre- eclamptic women have lower FMD and have HF-B more often compared with healthy parous controls. Nonetheless, HF-B was not related to reduced FMD. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prevalence of asymptomatic heart failure in formerly pre-eclamptic women: a cohort study.

OBJECTIVES: After pre-eclampsia (PE), the prevalence of structural heart disease without symptoms, i.e. heart failure Stage B (HF-B), may be as high as one in four women in the first year postpartum. We hypothesize that a significant number of formerly pre-eclamptic women with HF-B postpartum are still in their resolving period and will not have HF-B during follow-up. METHODS: In this prospective longitudinal cohort study, we included 69 formerly pre-eclamptic women who underwent serial echocardiographic measurements at 1 and 4 years postpartum. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m2 ), concentric remodeling (relative wall thickness > 0.42 and LVMi ≤ 95 g/m2 ), mild systolic dysfunction (left ventricular ejection fraction > 40% and < 55%) or asymptomatic valvular disease. Women were subdivided and analyzed according to HF-B outcome: no HF-B at either visit; HF-B at first visit only; HF-B at second visit only; HF-B at both visits. RESULTS: The prevalence of HF-B in formerly pre-eclamptic women was 23% in the first year postpartum and 23% after 4 years. At the second visit, HF-B had resolved in 62.5% of affected women but was newly developed in 19% of initially unaffected women. At the first visit, 56% of women diagnosed with HF-B had reduced systolic function whereas at the second visit 69% of women with HF-B had concentric remodeling with mostly normal ejection fraction, consistent with diastolic dysfunction. CONCLUSIONS: The prevalence of HF-B can be considered consistently high (1 in 4) amongst formerly pre-eclamptic women at follow-up. Nonetheless, at an individual level, more than 60% of women found initially to be affected by HF-B will recover, whilst about 20% of formerly pre-eclamptic women with normal echocardiography in the first year postpartum will develop HF-B over the following years. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Pre-eclampsia: an important risk factor for asymptomatic heart failure.

OBJECTIVES: Pre-eclampsia (PE) is associated with both postpartum structural asymptomatic heart disease (i.e. heart failure Stage B (HF-B)) and conventional cardiovascular (CV) risk factors. We aimed to evaluate the extent to which PE, adjusted for conventional CV risk factors, is associated independently with asymptomatic cardiac abnormalities postpartum. METHODS: In this cross-sectional cohort study, 107 formerly pre-eclamptic women and 41 women with uneventful previous pregnancy (controls) were invited for CV risk assessment 4-10 years postpartum. This included cardiac ultrasound, blood pressure (BP) measurement and evaluation of metabolic syndrome determinants. Asymptomatic structural and functional cardiac abnormalities were classified as HF-B, according to the American Heart Association guidelines. Prehypertension was defined as systolic BP of 120-139 mmHg and/or diastolic BP of 80-89 mmHg. Univariate and multivariate regression analyses were performed to calculate associations of PE and conventional risk factors with HF-B. RESULTS: The prevalence of asymptomatic HF-B was approximately 3.5-fold higher in the PE group compared with controls (25% vs 7%, P < 0.01); 67% of this group had concentric remodeling and 22% had mildly impaired ejection fraction. After adjustment for postpartum interval, hypertension and high-density lipoprotein, PE was significantly associated with HF-B (adjusted odds ratio, 4.4 (95% CI, 1.0-19.1)). Moreover, in the formerly pre-eclamptic group, prehypertension was associated significantly with HF-B (odds ratio, 4.3 (95% CI, 1.4-12.7)), while metabolic syndrome determinants were not. CONCLUSION: PE is associated with a four-fold increased female-specific risk of asymptomatic cardiac abnormalities. Prehypertension apparently increases this risk significantly, while metabolic syndrome determinants do not. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cardiovascular disease risk is only elevated in hypertensive, formerly preeclamptic women.

OBJECTIVE: To analyse the predicted 10- and 30-year risk scores for cardiovascular disease (CVD) in patients who experienced preeclampsia (PE) 5-10 years previously compared with healthy parous controls. DESIGN: Observational study. SETTING: Tertiary referral hospital in the Netherlands. POPULATION: One hundred and fifteen patients with a history of PE and 50 controls. PE patients were categorised into two groups, hypertensive (n = 21) and normotensive (n = 94), based on use of antihypertensive medication, and next categorised into subgroups based on the onset of PE: early-onset PE (n = 39) and late-onset PE (n = 76). METHODS: All participants underwent cardiovascular risk screening 5-10 years after index pregnancy. We measured body mass, height and blood pressure. Blood was analysed for fasting glucose, insulin and lipid levels. All participants completed a validated questionnaire. The 10- and 30-year Framingham risk scores were calculated and compared. MAIN OUTCOME MEASURES: Estimated Framingham 10- and 30-year risk scores for CVD. RESULTS: The overall 10- and 30-year CVD median risks weighing subjects' lipids were comparable between formerly PE women and controls; 1.6 versus 1.5% (P = 0.22) and 9.0 versus 9.0% (P = 0.49), respectively. However, hypertensive formerly PE women have twice the CVD risk as normotensive formerly PE women: 10- and 30-year CVD median risks were 3.1 versus 1.5% (P < 0.01) and 19.0% versus 8.0% (P < 0.01), respectively. Risk estimates based on BMI rather than lipid profile show comparable results. Early-onset PE clustered more often in the hypertensive formerly PE group and showed significantly higher 10- and 30-year CVD risk estimates based on lipids compared with the late-onset PE group: 1.7 versus 1.3% (P < 0.05) and 10.0 versus 7.0% (P < 0.05), respectively. CONCLUSIONS: Women who are hypertensive after preeclampsia, have a twofold risk of developing CVD in the next 10-30 years. Formerly PE women who are normotensive in the first 10 years after their preeclamptic pregnancy have a comparable future cardiovascular risk to healthy controls.

Metabolic syndrome and the risk for recurrent pre-eclampsia: a retrospective cohort study.

OBJECTIVE: To compare the prevalence of recurrent pre-eclampsia between women who have and do not have metabolic syndrome when non-pregnant. DESIGN: Retrospective cohort study. SETTING: Three tertiary referral hospitals in the Netherlands. POPULATION: Formerly pre-eclamptic women. METHODS: The presence or absence of metabolic syndrome was assessed in 480 women at least 6 months after their first pre-eclamptic pregnancy using World Health Organization criteria. We compared the prevalence of recurrent pre-eclampsia in the subsequent pregnancy, calculating odds ratios (OR), adjusted for confounders. MAIN OUTCOME MEASURE: Recurrence of pre-eclampsia in the subsequent pregnancy. RESULTS: Subsequent pregnancy outcome data were available for 197 women. Forty women had metabolic syndrome after previous pregnancy (20%). The prevalence of recurrent pre-eclampsia was 18/40 (45%) in women with metabolic syndrome versus 27/157 (17%) in women without metabolic syndrome; OR 3.94 (95% confidence interval [CI] 1.86-8.33, adjusted OR 3.77 (95% CI 1.61-8.81). The risk of recurrent pre-eclampsia increased with each extra component of the metabolic syndrome from 11.8% for absent components up to 43.9% for three or more (P for trend < 0.001). CONCLUSIONS: Interpregnancy metabolic syndrome predisposes to recurrent pre-eclampsia.

Reperfusion therapy for acute myocardial infarction. Which strategy for which patient?

Several modes of reperfusion therapy for evolving myocardial infarction (MI) have been developed, which differ in terms of effectiveness, complexity and costs. Reperfusion resources are often restricted by budgetary or logistical circumstances. To arrive at an equitable distribution of treatment options, physicians should therefore consider which treatment to apply in which patient. Two major questions which arise in this respect are discussed here: what is the treatment effect in an individual patients, and what is an equitable resource allocation? Currently, the most relevant treatment options are: streptokinase (1.5MU over 1h), reteplase (2 boluses of 10MU), alteplase (tissue plasminogen activator; t-PA) [100mg over 1.5 hours] and immediate angioplasty. In combination with aspirin, streptokinase leads to an almost 40% mortality reduction at 1 month compared with placebo [from 13.2 to 8.0%; Second International Study of Infarct Survival (ISIS-2) trial]. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-1) study demonstrated a further mortality reduction by early combination therapy of aspirin, intravenous heparin and alteplase vs aspirin, heparin (either intravenous or subcutaneous) plus streptokinase (from 7.3 to 6.3%). The clinical effects of reteplase fall somewhere between those of streptokinase and alteplase. Combined analysis of the angioplasty trials suggests that angioplasty is superior to thrombolysis, especially in patients with a high cerebral bleeding risk. The noticed gradient of efficacy runs parallel to a gradient of costs and complexity: streptokinase is the least costly treatment option while direct angioplasty is the most expensive and complex. Subgroup analyses indicate that there are neither apparent deviations in the relative effect of reperfusion therapy as compared to control treatment, nor in the additional effect of more intensive therapy (alteplase) upon 'standard' therapy (streptokinase). Consequently, the absolute number of deaths avoided by reperfusion therapy appears to be greatest in those groups with a high mortality risk without therapy. There is one major exception: in patients treated early after symptom onset a much greater relative mortality reduction is observed than in those treated later. Owing to the higher mortality risk, the life expectancy of a patient with MI is shorter than that of an 'average' person of the same community and the same age. Since mortality reduction of reperfusion therapy is maintained at long term follow-up, part of this potential loss can be regained. This 're-gain of lost years' is judged to be the ultimate treatment effect in an individual patient. An equitable treatment allocation should be such that patients who will benefit most will receive the most effective therapy, while patients with similar expected benefit will be offered the same mode of therapy. The conclusion is that treatment guidelines or protocols can be very useful in clinical practice, especially if rapid decision making is of vital importance.

Characteristics of smokers and long-term changes in smoking behavior in consecutive patients with myocardial infarction.

BACKGROUND: The prognosis of patients with estabLished coronary artery improves if smoking is stopped. Still, about half of patients who suffer a myocardial infarction continue smoking after that event. In order to predict to whom additional support should be offered, various baseline characteristics were compared with smoking status at short-term and long-term follow-up. METHODS: Demographics, medical history, presence of coronary risk factors, psychological determinants, and the clinical course were recorded in a group of 530 unselected consecutive patients who had been admitted with a myocardial infarction and were smoking. Patients who were smoking at admission, and who were alive at 4-year follow-up, were studied to relate smoking status and baseline characteristics. RESULTS: At 3 months, persistent smokers were younger than quitters, had shorter hospital stays, underwent revascularization procedures less often, smoked more cigarettes per day at baseline, and were more socially isolated. After 4 years, patients who stopped smoking had had a more serious myocardial infarction and had a lower displeasure score than those who continued smoking. Also, quitters received more support from their social environment. CONCLUSIONS: Although the majority of the patients try to stop smoking after a myocardial infarction, about half smokes after 4 years. In the future, special support should be offered to smokers who suffer myocardial infarction, especially to those whose psychosocial profiles are less favorable.

Estimated gain in life expectancy. A simple tool to select optimal reperfusion treatment in individual patients with evolving myocardial infarction.

Currently several modes of reperfusion therapy for acute myocardial infarction are available. Streptokinase, accelerated alteplase and direct angioplasty are the most frequently used. These options are increasingly effective, but are also increasingly complex and costly. Since, unfortunately, physicians are often restricted by budget limitations, choices must be made in clinical practice to provide optimal therapy to individual patients. In order to guide such decision making, we developed a model to predict the expected benefit of therapy in terms of gain in life expectancy. Patients' life expectancy will decrease after infarction. Part of this loss can be prevented by early reperfusion therapy. The clinical benefit of therapy ranges from negligible gain in patients with small infarcts treated relatively late to an expected gain of more than 2 years in patients with extensive infarction treated within 3 h of onset of symptoms. The expected benefits are presented in a set of tables and depend on age, previous infarction, estimated infarct size, treatment delay and intracranial bleeding risk. With the help of these table, resources will be allocated in such a manner that patients who will benefit the most will receive the most effective therapy. Patients with similar expected treatment benefit will be offered the same mode of therapy. Future life years were discounted at 5% per year. The arbitrary thresholds currently applied for decision making at the Thoraxcenter are: no reperfusion therapy when the estimated gain in discounted life expectancy was < 1 month, streptokinase for 1-4 months and accelerated alteplase for a gain > or = 5 months. Direct angioplasty is recommended in patients with an estimated gain > or = 12 months, and in patients with an increased risk of intracranial bleeding. In this way, approximately 80% of our patients will be treated with thrombolytics (40% streptokinase and 40% accelerated alteplase), while in 10% direct angioplasty will be initiated. Patients with small infarcts presenting late will not receive reperfusion therapy. These threshold values have been chosen arbitrarily, and different thresholds may be selected in other centres. However, the developed model would guarantee that treatment decisions are made in a consistent manner, to provide optimal therapy for patients with evolving myocardial infarction, in spite of limited resources.

Prospective study of early discharge after acute myocardial infarction (SHORT)

AIMS: To identify, without additional investigation, a large group of myocardial infarction patients at low risk who would qualify for early discharge. METHODS: The decision rule was developed in 647 unselected patients with consecutively admitted myocardial infarction, and validated in 825 others. Daily event-rates were calculated for major (death, ventricular fibrillation, recurrent infarction, heart failure, advanced AV-block) and minor (unstable angina and rhythm-abnormalities) cardiac complications. RESULTS: Patients free from major complications until day 7 (44% of all patients) were found to constitute a very low risk group and thus would qualify for discharge at day 7. Of the 39% of patients with an uncomplicated infarction (low risk) in the validation group, 31% were discharged at day 7, while 8% stayed longer because of non-cardiac co-morbidity, for social reasons or logistic problems. No major adverse event occurred within 7 days after hospital discharge and only 1.8% developed complications within 1 month. The median duration of hospital stay for all in-hospital survivors was 7 days compared to 10 days in the control group. CONCLUSION: Prospective application of the early discharge decision rule, based upon simple clinical variables and without the need for additional non-invasive and/or invasive tests, resulted in a significant reduction of hospital stay. The decision rule correctly classified patients into high and low risk groups and appeared feasible and safe. Its efficacy was demonstrated by its ability to identify a large group of post infarction survivors at low risk for complications during follow-up.