Preeclampsia as a risk factor for cardiovascular disease later in life: validation of a preeclampsia questionnaire.

OBJECTIVE: This study was undertaken to validate a self-administered questionnaire in verifying the diagnosis of preeclampsia, eclampsia, or toxemia in a group of women with a greater than 20-year history of preeclampsia. STUDY DESIGN: Questionnaires were mailed to a random sample of 144 women who received a diagnosis of any of these 3 conditions and 158 women who had normotensive pregnancies at Mayo Clinic, Rochester, Minnesota, from 1960-1979. RESULTS: A previous diagnosis of preeclampsia, eclampsia, or toxemia was verified with 80% sensitivity and 96% specificity. CONCLUSION: Our validated questionnaire may be a useful research tool in identifying women with a previous history of preeclampsia. Women with a history of preeclampsia had a higher prevalence of future hypertension than those with a history of normotensive pregnancy.

Four-year recurrence rate and prognosis of the apical ballooning syndrome.

OBJECTIVES: This study sought to assess the long-term prognosis of patients with apical ballooning syndrome (ABS). BACKGROUND: Apical ballooning syndrome is a recently described acute cardiac syndrome of uncertain etiology and prognosis. METHODS: We retrospectively identified 100 unselected patients with a confirmed diagnosis of ABS by angiography. Recurrences of ABS and mortality were recorded. RESULTS: Over a mean follow-up of 4.4 +/- 4.6 years, 31 patients continued to have episodes of chest pain and 10 patients had recurrence of ABS, for a recurrence rate of 11.4% over the first 4 years. Seventeen patients died in 4.7 +/- 4.8 years of follow-up. There was no difference in survival or in cardiovascular survival to an age- and gender-matched population. CONCLUSIONS: The recurrence rate for ABS was 11.4% over 4 years after initial presentation. Recurrence of chest pain is common. Four-year survival was not different from that in an age-matched and gender-matched population.

Coronary endothelial dysfunction and hyperlipidemia are independently associated with diastolic dysfunction in humans.

BACKGROUND: Coronary endothelial dysfunction (CED) and DHF are both associated with myocardial ischemia and CAD risk factors. The objective of the this study was to determine if CED and CAD factors are associated with diastolic dysfunction before the development of occlusive CAD or clinical heart failure. METHODS: Patients with normal ejection fraction and nonocclusive CAD who underwent coronary endothelial function studies were identified. Left ventricular relaxation was assessed by tissue Doppler assessment of early diastolic ascent of the septal mitral annulus (Ea). Multiple linear regression was used to investigate whether coronary risk factors influenced diastolic function after adjusting for the presence of CED. RESULTS: A total of 160 patients had adequate assessment of diastolic relaxation. With multiple linear regression models, %deltaCBF (P = .018) was associated with a higher Ea; in contrast, older age (P < .001), female sex (P = .028), higher left ventricular mass index (P = .016), and higher nonhigh-density lipoprotein cholesterol (P = .022) were associated with a lower Ea. CONCLUSION: Coronary endothelial dysfunction and hyperlipidemia are independently associated with impaired relaxation in patients with normal ejection fraction in the absence of occlusive CAD and heart failure. The current study suggests a new potential mechanism for the development of endothelial and diastolic dysfunction in humans.

Pregnancy associated plasma protein-A and risk stratification of patients presenting with chest pain in the emergency department.

BACKGROUND: The aim of this study was to evaluate the clinical utility of serum pregnancy associated plasma protein-A (PAPP-A) levels in assisting triage of an intermediate to high-risk patient presenting with chest pain in the Emergency Department and no definite evidence of an acute coronary syndrome. METHODS: Serum levels of PAPP-A were measured in 59 patients presenting with chest pain to the Emergency Department. The patients were independently grouped according to the presence of acute coronary syndromes or the absence thereof. RESULTS: In a multivariate model that corrected for age, sex, type of chest pain, number of risk factors, history of coronary artery disease, troponin levels, and non-specific ECG changes, PAPP-A levels were still predictive of a final diagnosis of acute coronary syndrome in patients presenting with chest pain to the Emergency Department (Odds Ratio, 2.093; 95th confidence intervals, 1.037-4.224; p=0.039). CONCLUSIONS: Elevated serum PAPP-A levels were predictive of a diagnosis of acute coronary syndrome in intermediate- to high-risk patients presenting to the Emergency Department with chest pain and no definite evidence of an acute coronary syndrome. Thus, serum PAPP-A may be valuable as an adjunct, minimally invasive marker to improve risk stratification in chest pain patients.

A comparative analysis of short- and long-term outcomes after ventricular fibrillation out-of-hospital cardiac arrest in patients with ischemic and nonischemic heart disease.

Although ventricular fibrillation (VF) out-of-hospital cardiac arrest (OHCA) occurs primarily in the setting of severe ischemic heart disease (IHD), a significant proportion of events occurs in patients who do not have severe IHD. The relative effect of IHD on survival after VF OHCA is unknown. All residents of Rochester, Minnesota, who presented with a VF OHCA from November 1990 to December 2004, treated by emergency medical services, were included in the study. During the study, emergency medical services treated 208 patients (64.1 +/- 13.6 years of age) for VF OHCA, with an average call-to-shock time of 6.3 +/- 1.8 minutes. Of these patients, 156 had IHD and 39 had non-IHD. In 13, the underlying heart disease was unknown. Eighty-seven patients (41.8%) survived to hospital discharge with neurologic recovery (66 with IDH [42%] vs 21 with non-IHD [54%], p = 0.211)]. Five-year survival was 79 +/- 6% for patients with IHD versus 100% for those with non-IHD (p = 0.047). After adjustment for other patient characteristics, IHD was not predictive of 5-year survival (hazard ratio [HR] 2.2, 95% confidence interval [CI] 0.7 to 9.8, p = 0.177). Variables associated with poor outcomes included age >65 years (HR 4.9, 95% CI 2.0 to 13.4, p = 0.0003), ejection fraction <0.35% (HR 3.0, 95% CI 1.3 to 7.3, p = 0.012), and hypertension (HR 4.9, 95% CI 1.4 to 16.3, p = 0.001). In patients with IHD, use of an implantable cardioverter-defibrillator (HR 0.32, 95% CI 0.16 to 0.88, p = 0.024) and statin therapy (HR 0.68, 95% CI 0.17 to 0.73, p = 0.001) were associated with decreased mortality. In conclusion, compared with patients with non-IHD, those with IHD had similar short- and long-term survival rates. Long-term survival in patients with IHD was primarily influenced by other co-morbid conditions. Nonetheless, in patients with IHD, use of an implantable cardioverter-defibrillator and statin therapy were associated with higher long-term survival rates.

Prognostic value of circulating pregnancy-associated plasma protein levels in patients with chronic stable angina.

AIMS: Unstable coronary atherosclerotic plaque can be present in patients with chronic stable coronary artery disease (CAD). Our objective was to assess whether measurement of plasma pregnancy-associated plasma protein (PAPP-A) level, a reflection of plaque instability, in patients with chronic stable CAD had an independent prognostic value on the subsequent incidence of death, acute coronary syndrome (ACS), and revascularization. METHODS AND RESULTS: Patients referred for coronary angiography were recruited. A cohort of 103 patients with stable symptoms for at least 6 weeks and with a coronary angiogram showing at least a 50% luminal diameter narrowing formed our study population. Median follow-up was 4.9 years. Mean age was 65+/-10 years. In a multivariable model that included CAD traditional risk factors, ejection fraction, extent of coronary atherosclerosis, prior history of myocardial infarction, prior revascularization, discharge medications, and C-reactive protein, the plasma PAPP-A was found to be significantly associated with the endpoint of future death [adjusted hazard ratio (HR) 5.29; 95% CI 1.27-22.0; P=0.023] and with the endpoint of future death and ACS (adjusted HR 3.56; 95% CI 1.27-10.0; P=0.015), but not with the endpoint of future death and revascularization. CONCLUSION: Measurement of plasma PAPP-A level in patients with chronic stable CAD has an independent prognostic value on the occurrence of death and ACS.

Endothelial function and cerebrovascular disease: implications for diagnosis and treatment.

Cerebrovascular disease remains one of the most common causes of morbidity and mortality in the United States. There is strong evidence to implicate endothelial dysfunction in the initiation and progression of atherosclerosis and its complications. It is now well known that endothelial dysfunction represents a systemic syndrome involving multiple vascular beds, including the cerebral vasculature. Currently, no gold standard treatment for endothelial dysfunction exists. Nonetheless, several treatment strategies have been found to be helpful in improving endothelial function. A few of these strategies have been implicated in stroke risk reduction as well, adding another line of evidence to the relationship between endothelial function and cerebrovascular disease.

Plasma 8-iso-prostaglandin F2alpha, a marker of oxidative stress, is increased in patients with acute myocardial infarction.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of atherogenesis. The aim of our study is to examine whether the plasma 8-iso-prostaglandin F(2alpha) level, a marker of oxidative stress, is elevated in patients with acute myocardial infarction. METHODS: Three groups of patients were enrolled: (1) patients with no or minimal coronary artery disease (CAD) (n = 15); (2) patients with stable CAD (n = 31); (3) patients with acute myocardial infarction (n = 13). RESULTS: Plasma 8-iso-prostaglandin F(2alpha) levels were significantly elevated (p < 0.001) in patients with acute myocardial infarction (290.7 +/- 73.9 pg/ml) as compared to patients with stable CAD (182.0+75.7 pg/ml) and patients with no significant CAD (118.9 +/- 85.5 pg/ml). This remained significant after correcting for coronary atherosclerosis risk factors, age, extent of atherosclerosis, and C-reactive protein (CRP) level. CONCLUSION: Plasma 8-iso-prostaglandin F(2alpha) levels are elevated in patients with acute myocardial infarction. Endogenous oxidative stress may contribute to the pathogenesis of atherosclerosis and its complications, namely myocardial infarction.

Relapse and mortality following cardioversion of new-onset vs. recurrent atrial fibrillation and atrial flutter in the elderly.

AIMS: Trials of rate control vs. rhythm control for atrial fibrillation or flutter included few patients with new-onset arrhythmia. Our objective was to assess the relapse rate and the effect of the relapse of new-onset atrial arrhythmias on mortality after direct-current cardioversion (DCCV). METHODS AND RESULTS: A cohort of 351 patients with atrial fibrillation (new onset in 179) and 126 patients with atrial flutter (new onset in 78) was followed-up after DCCV. Cox proportional hazard models were used. Median age was 74.6 years. Mean follow-up for relapse was 7.7 months; for death, 29.4 months. Patients with new-onset atrial flutter [adjusted hazard ratio (HR) = 1] were more likely to maintain sinus rhythm than the patients with recurrent atrial flutter (adjusted HR = 2.5, P < 0.01), new-onset atrial fibrillation (adjusted HR = 2.4, P < 0.01), or recurrent atrial fibrillation (adjusted HR = 2.7, P < 0.01). Patients with new-onset atrial fibrillation were as likely to have relapses as patients with recurrent atrial fibrillation or flutter. Relapse of atrial arrhythmia after DCCV was associated with increased mortality (adjusted HR= 3.1, P < 0.01). CONCLUSION: DCCV is more successful in maintaining sinus rhythm in patients with new-onset atrial flutter than in patients with new-onset atrial fibrillation. Relapse of atrial arrhythmia after cardioversion is associated with increased mortality.

Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis.

AIMS: Coronary endothelial dysfunction (CED) precedes atherosclerosis and is associated with cardiovascular events. Both CED and erectile dysfunction (ED) are partly mediated by impairment in the nitric oxide pathway. ED is associated with established coronary atherosclerosis, but its relationship with early coronary atherosclerosis and CED is unknown. This study was designed to test the hypothesis that CED is associated with ED in men with early coronary atherosclerosis. Moreover, the role of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) was investigated; ADMA is a novel endogenous competitive inhibitor of nitric oxide synthase and has been shown to be an independent marker for cardiovascular disease. METHODS AND RESULTS: Fifty-six men without obstructive coronary artery disease (CAD) who underwent coronary endothelial function testing were studied. ADMA levels were determined and all men were asked to complete the International Index of Erectile Function-5 questionnaire to assess erectile function. Patients were divided according to the presence (n = 32) or absence (n = 24) of CED. Men with CED had significant impairment of erectile function (P = 0.008) and significantly higher ADMA levels (0.50 +/- 0.06 vs. 0.45 +/- 0.07 ng/mL, P = 0.017) compared with men with normal endothelial function. Erectile function positively correlated with coronary endothelial function. This correlation was independent of age, body mass index, high-density lipoprotein, C-reactive protein, homeostasis model assessment of insulin resistance index, and smoking status. CONCLUSION: CED is independently associated with ED and plasma ADMA concentration in men with early coronary atherosclerosis. This study further supports the role of the endothelium in systemic vascular diseases and the role of ADMA in the systemic manifestations of endothelial dysfunction.

Bosentan preserves endothelial function in mice overexpressing APP.

This study was designed to test the hypothesis that Alzheimer's disease (AD) is associated with endothelial dysfunction and that chronic endothelin-1 antagonism preserves endothelial function in mice overexpressing the AD amyloid precursor protein (APP). Three groups of mice were studied: C57BL/6 (normal control, n = 6), transgenic mice overexpressing APP (Tg2576, n = 5), and Tg2576 mice fed Bosentan (100 mg/(kg day)(-1)), a combined endothelin A and B receptor antagonist, for 4 months (Tg2576+Bosentan, n = 5). Mice were sacrificed at the age of 7 months. In vitro, the endothelium-dependent aortic vasorelaxation was significantly attenuated in Tg2576 mice as compared to C57BL/6 and Tg2576+Bosentan mice. In contrast, Tg2576+Bosentan and C57BL/6 mice showed similar endothelium-dependent aortic vasorelaxation. Similarly, endothelium-dependent carotid vasorelaxation was significantly attenuated in Tg2576 mice compared to C57BL/6 and Tg2576+Bosentan mice. There was no difference between the three groups in the response to nitroprusside. The current study demonstrates the presence of endothelial dysfunction in both carotid and aortic arteries in mice overexpressing APP and suggests a pathophysiological role for the endogenous endothelin system in AD.

Incidence, retrieval methods, and outcomes of stent loss during percutaneous coronary intervention: a large single-center experience.

Our goal was to examine the incidence and consequences of stent loss during percutaneous coronary intervention (PCI) and the retrieval techniques used. We retrospectively reviewed 11,773 consecutive PCI cases involving stents performed at our institution between January 1994 and March 2004 to identify cases of stent loss. Stent loss occurred in 38 of 11,773 PCI procedures involving stents (0.32%; 95% CI = 0.23-0.44%). Mean age of the patients was 67 +/- 11 years and 82% were men. Stent loss occurred more frequently in lesions with calcification and/or significant proximal angulation. In three patients, the stent was crushed and covered with another stent without attempting retrieval. Stent retrieval was attempted in 35 of 38 cases and was successful in 30 (86%). The following retrieval methods were used (more than one method was used in some cases): advancing a balloon through the stent, inflating the balloon, and withdrawing the stent (45%); twirling two wires around the stent (5%); loop snare (26%); biliary forceps (12%); Cook retained fragment retriever (10%); and basket retrieval device (2%). Patients in whom stent loss occurred had a higher incidence of bleeding requiring transfusion (24% vs. 7%; P < 0.001) and more often required emergency coronary artery bypass surgery (5% vs. 0.4%; P < 0.001). No patients in whom the stent was crushed or deployed in the coronary artery had any major cardiac complication. Stent loss during PCI occurs infrequently. Lost stents can be successfully retrieved in the majority of cases using a variety of retrieval techniques, yet stent loss is associated with an increased risk of complications. Stent deployment or crushing may be a good alternative to retrieval.

Impact of the application of the American College of Emergency Physicians recommendations for the admission of patients with syncope on a retrospectively studied population presenting to the emergency department.

BACKGROUND: The goal of our study was to determine the accuracy of the American College of Emergency Physicians (ACEP) clinical policy in identifying patients with a cardiac cause for their syncope and its potential effect on syncope management. METHODS: Adult patients with syncope presenting to the emergency department (ED) from January 1996 to December 1998 were identified. Diagnosis was established retrospectively by reviewing medical records. The ACEP guidelines were applied to this population. RESULTS: Of the 200 patients identified, 115 (57.5%, 95% CI 60-64) were admitted from the ED and 24 (12%) were found to have cardiogenic syncope. Of the 24 patients with cardiac syncope, 23 were admitted. By applying ACEP level B recommendations to our population, all patients who on further workup were found to have cardiac syncope would have been admitted from the ED (100% sensitivity, 95% CI 86-100) and 81% of patients with no cardiac syncope would have been discharged from the ED (81% specificity, 95% CI 75-87). The admission rate would have been 28.5% (95% CI 22-35). By extending admission to patients satisfying level C in addition to level B recommendations, the sensitivity, specificity, and admission rate would have been 100% (95% CI 86-100), 33% (95% CI 26-40), and 71.0% (95% CI 64-77), respectively. CONCLUSION: High sensitivity and specificity in identifying patients with cardiogenic syncope and significant reduction in the hospital admission rate were observed by applying ACEP level B recommendations to patients presenting to our ED. Application of level C recommendations did not offer any advantage.

Noninvasive assessment of acute changes in atrial electrophysiology after cardioversion by signal-averaged P-wave electrocardiography.

BACKGROUND: Atrial remodeling secondary to atrial fibrillation (AF) may be important in the arrhythmogenic process. Unfortunately, the study of electrophysiologic remodeling in humans has been limited by the invasive nature of most tests of electrophysiologic characteristics. We sought to determine whether changes in atrial electrophysiology occur acutely (within the first hour) after cardioversion and whether these changes could be detected noninvasively by measuring the signal-averaged P-wave. METHODS: The filtered P-wave duration (FPD) was measured by signal-averaged electrocardiography (ECG) at 20 and 60 minutes after cardioversion in 46 patients with AF, and the difference between the two values was calculated. The root-mean-square voltage of the terminal 40 ms of the signal-averaged P-wave at 20 and 60 minutes and the difference between them were also determined. RESULTS: The FPD at 20 minutes was significantly different from that at 60 minutes (153.0 +/- 19.1 vs 159.7 +/- 24.8 ms; P = 0.02). In a univariate linear regression model, none of the clinical variables studied was significantly associated with the change in FPD. The root-mean-square voltage at 20 minutes was not significantly different from that at 60 minutes (5.8 +/- 3.0 vs 5.5 +/- 2.7; P = 0.14). CONCLUSIONS: We conclude that significant changes in atrial electrophysiology occur within the first hour after cardioversion of AF. These changes can be detected by measuring the FPD.

Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease risk factors, angiographic coronary artery disease, and major adverse events at follow-up.

AIMS: We aimed to evaluate the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with coronary artery disease (CAD) risk factors, with the severity of angiographic CAD, and with the incidence of major adverse events. METHODS AND RESULTS: We measured Lp-PLA2 levels in 504 consecutive patients undergoing clinically indicated coronary angiography. Mean age was 60+/-11 years and 38% were women. The mean (+/-SD) Lp-PLA2 level (ng/mL) was 245+/-91. Lp-PLA2 levels correlated with male gender, LDL, HDL, and total cholesterol, fibrinogen, and creatinine. Lp-PLA2 levels correlated with the extent of angiographic CAD on univariate but not on multivariable analysis. During a median follow-up of 4.0 years, 72 major adverse events occurred in 61 of 466 (13%) contacted patients (20 deaths, 14 myocardial infarctions, 28 coronary revascularizations, and 10 strokes). Higher Lp-PLA2 levels were associated with a greater risk of events: the hazard ratio per SD was 1.28 (95% CI 1.06-1.54, P=0.009), and remained significant after adjusting for clinical and lipid variables and C-reactive protein. CONCLUSION: Higher Lp-PLA2 levels were associated with a higher incidence of major adverse events at follow-up, independently of traditional CAD risk factors and C-reactive protein.