Preeclampsia and cognitive impairment later in life Fields, Julie A., PhD; Garovic, Vesna D., MD; Mielke, Michelle M., PhD ...
American journal of obstetrics and gynecology,
07/2017, Letnik:
217, Številka:
1
Journal Article
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Background Hypertension is a risk factor for cerebrovascular disease and cognitive impairment. Women with hypertensive episodes during pregnancy report variable neurocognitive changes within the ...first decade following the affected pregnancy. However, long-term follow-up of these women into their postmenopausal years has not been conducted. Objective The aim of this study was to examine whether women with a history of preeclampsia were at increased risk of cognitive decline 35-40 years after the affected pregnancy. Study Design Women were identified and recruited through the medical linkage, population-based Rochester Epidemiologic Project. Forty women with a history of preeclampsia were age- and parity-matched to 40 women with a history of normotensive pregnancy. All women underwent comprehensive neuropsychological assessment and completed self-report inventories measuring mood, ie, depression, anxiety, and other symptoms related to emotional state. Scores were compared between groups. In addition, individual cognitive scores were examined by neuropsychologists and a neurologist blinded to pregnancy status, and a clinical consensus diagnosis of normal, mild cognitive impairment, or dementia for each participant was conferred. Results Age at time of consent did not differ between preeclampsia (59.2 range 50.9-71.5 years) and normotensive (59.6 range 52.1-72.2 years) groups, nor did time from index pregnancy (34.9 range 32.0-47.2 vs 34.5 range 32.0-46.4 years, respectively). There were no statistically significant differences in raw scores on tests of cognition and mood between women with histories of preeclampsia compared to women with histories of normotensive pregnancy. However, a consensus diagnosis of mild cognitive impairment or dementia trended toward greater frequency in women with histories of preeclampsia compared to those with normotensive pregnancies (20% vs 8%, P = .10) and affected more domains among the preeclampsia group ( P = .03), most strongly related to executive dysfunction ( d = 1.96) and verbal list learning impairment ( d = 1.93). Conclusion These findings suggest a trend for women with a history of preeclampsia to exhibit more cognitive impairment later in life than those with a history of normotensive pregnancy. Furthermore, the pattern of cognitive changes is consistent with that observed with vascular disease/white matter pathology.
Background A history of preeclampsia is an independent risk factor for cardiac events and stroke. Changes in vasculature structure that contribute to these associations are not well understood. ...Objective The aim of this study was to quantify coronary artery calcification (CAC), a known risk factor for cardiac events, in a prospective cohort of women with and without histories of preeclampsia. Study Design Women without prior cardiovascular events (40 with and 40 without histories of preeclampsia, matched for parity and age at index birth) were recruited from a large population-based cohort of women who were residents of Olmsted County, Minnesota, and who delivered from 1976 through 1982. Computed tomography was performed to measure CAC in Agatston units. All pregnancy histories and covariates were confirmed by review of the medical records. Current clinical variables were assessed at the time of imaging. Differences between women with and without histories of preeclampsia were examined using χ2 tests and tests; CAC, in particular, was compared as a categorical and ordinal variable, with a χ2 test and with Wilcoxon 2-sample tests and ordinal logistic regression, as appropriate. Results Mean age (SD) at imaging was 59.5 (±4.6) years. Systolic and diastolic blood pressures, hyperlipidemia, and current diabetes status did not differ between women with and without histories of preeclampsia. However, the frequencies of having a current clinical diagnosis of hypertension (60% vs 20%, P < .001) and higher body mass index in kg/m2 (29.8; interquartile range, 25.9-33.7 vs 25.3; interquartile range, 23.1-32.0, median 25th-75th percentile, P = .023) were both greater in the women with histories of preeclampsia compared to those without. The frequency of a CAC score >50 Agatston units was also greater in the preeclampsia group (23% vs 0%, P = .001). Compared to women without preeclampsia, the odds of having a higher CAC score was 3.54 (confidence interval CI, 1.39–9.02) times greater in women with prior preeclampsia without adjustment, and 2.61 (CI, 0.95–7.14) times greater after adjustment for current hypertension. After adjustment for body mass index alone, the odds of having a higher CAC based on a history of preeclampsia remained significant at 3.20 (CI, 1.21–8.49). Conclusion In this first prospective cohort study with confirmation of preeclampsia by medical record review, a history of preeclampsia is associated with an increased risk of CAC >30 years after affected pregnancies, even after controlling individually for traditional risk factors. A history of preeclampsia should be considered in risk assessment when initiating primary prevention strategies to reduce cardiovascular disease in women. Among women with histories of preeclampsia, the presence of CAC may be able to identify those at a particularly high cardiovascular risk, and should be the subject of future studies.
Background Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. Data are lacking on the long-term prognostic implications of POAF. We hypothesized that POAF, which ...reflects underlying cardiovascular pathophysiologic substrate, is a predictive marker of late AF and long-term mortality. Methods We identified 603 Olmsted County, Minnesota, residents without prior documented history of AF who underwent coronary artery bypass graft and/or valve surgery from 2000 to 2005. Patients were monitored for first documentation of late AF or death at >30 days postoperatively. Multivariate Cox regression models were used to assess the independent association of POAF with late AF and long-term mortality. Results After a mean follow-up of 8.3 ± 4.2 years, freedom from late AF was less with POAF than no POAF (57.4% vs 88.9%, P < .001). The risk of late AF was highest within the first year at 18%. Univariate analysis demonstrated that POAF was associated with significantly increased risk of late AF hazard ratio (HR), 5.09; 95% CI, 3.65-7.22 and long-term mortality (HR, 1.79; 95% CI, 1.38-2.22). After adjustment for age, sex, and clinical and surgical risk factors, POAF remained independently associated with development of late AF (HR, 3.52; 95% CI, 2.42-5.13) but not long-term mortality (HR, 1.16; 95% CI, 0.87-1.55). Conversely, late AF was independently predictive of long-term mortality (HR, 3.25; 95% CI, 2.42-4.35). Diastolic dysfunction independently influenced the risk of late AF and long-term mortality. Conclusions Postoperative atrial fibrillation was an independent predictive marker of late AF, whereas late AF, but not POAF, was independently associated with long-term mortality. Patients who develop new-onset POAF should be considered for continuous anticoagulation at least during the first year following cardiac surgery.
Objectives We sought to define the cardiometabolic phenotype associated with rs5068, a genetic variant of the atrial natriuretic peptide (ANP) gene. Background The ANP and B-type natriuretic peptide ...play an important role in cardiorenal homeostasis but also exert metabolic actions. Methods We genotyped 1,608 randomly selected residents from Olmsted County, Minnesota. Subjects were well-characterized. Results Genotype frequencies were: AA 89.9%, AG 9.7%, and GG 0.4%; all subsequent analyses were AA versus AG+GG. The G allele was associated with increased plasma levels of N-terminal pro-atrial natriuretic peptide (p = 0.002), after adjustment for age and sex. The minor allele was also associated with lower body mass index (BMI) (p = 0.006), prevalence of obesity (p = 0.002), waist circumference (p = 0.021), lower levels of C-reactive protein (p = 0.027), and higher values of high-density lipoprotein cholesterol (p = 0.019). The AG+GG group had a lower systolic blood pressure (p = 0.011) and lower prevalence of myocardial infarction (p = 0.042). The minor allele was associated with a lower prevalence of metabolic syndrome (p = 0.025). The associations between the G allele and high-density lipoprotein cholesterol, C-reactive protein values, myocardial infarction, and metabolic syndrome were not significant, after adjusting for BMI; the associations with systolic blood pressure, BMI, obesity, and waist circumference remained significant even after adjusting for N-terminal pro-atrial natriuretic peptide. Conclusions In a random sample of the general U.S. population, the minor allele of rs5068 is associated with a favorable cardiometabolic profile. These findings suggest that rs5068 or genetic loci in linkage disequilibrium might affect susceptibility for cardiometabolic diseases and support the possible protective role of natriuretic peptides by their favorable effects on metabolic function. Replication studies are needed to confirm our findings.
Giant cell myocarditis (GCM) is a rare and highly lethal disorder. The only multicenter case series with treatment data lacked cardiac function assessments and had a retrospective design. We ...conducted a prospective, multicenter study of immunosuppression including cyclosporine and steroids for acute, microscopically-confirmed GCM. From June 1999 to June 2005 in a standard protocol, 11 subjects received high dose steroids and cyclosporine, and 9 subjects received muromonab-CD3. In these, 7 of 11 were women, the mean age was 60 ± 15 years, and the mean time from symptom onset to presentation was 27 ± 33 days. During 1 year of treatment, 1 subject died of respiratory complications on day 178, and 2 subjects received heart transplantations on days 2 and 27, respectively. Serial endomyocardial biopsies revealed that after 4 weeks of treatment the degree of necrosis, cellular inflammation, and giant cells decreased (p = 0.001). One patient who completed the trial subsequently died of a fatal GCM recurrence after withdrawal of immunosuppression. Her case demonstrates for the first time that there is a risk of recurrent, sometimes fatal, GCM after cessation of immunosuppression. In conclusion, this prospective study of immunosuppression for GCM confirms retrospective case reports that such therapy improves long-term survival. Additionally, withdrawal of immunosuppression can be associated with fatal GCM recurrence.
Objectives Our objective was to determine the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) for death and cardiovascular events among subjects without risk factors ...for heart failure (HF), which we term healthy normal. Background Previous studies report that plasma NT-proBNP has prognostic value for cardiovascular events in the general population even in the absence of HF. It is unclear if NT-proBNP retains predictive value in healthy normal subjects. Methods We identified a community-based cohort of 2,042 subjects in Olmsted County, Minnesota. Subjects with symptomatic (stage C/D) HF were excluded. The remaining 1,991 subjects underwent echocardiography and NT-proBNP measurement. We further defined healthy normal (n = 703) and stage A/B HF (n = 1,288) subgroups. Healthy normal was defined as the absence of traditional clinical cardiovascular risk factors and echocardiographic structural cardiac abnormalities. Subjects were followed for death, HF, cerebrovascular accident, and myocardial infarction with median follow-up of 9.1, 8.7, 8.8, and 8.9 years, respectively. Results NT-proBNP was not predictive of death or cardiovascular events in the healthy normal subgroup. Similar to previous reports, in stage A/B HF, plasma NT-proBNP values greater than age-/sex-specific 80th percentiles were associated with increased risk of death, HF, cerebrovascular accident, and myocardial infarction (p < 0.001 for all) even after adjustment for clinical risk factors and structural cardiac abnormalities. Conclusions These findings do not support the use of NT-proBNP as a cardiovascular biomarker in healthy normal subjects and have important implications for NT-proBNP–based strategies for early detection and primary prevention of cardiovascular disease.
Abstract Purpose The purpose of this study is to estimate medical costs attributable to venous thromboembolism among patients with active cancer. Methods In a population-based cohort study, we used ...Rochester Epidemiology Project (REP) resources to identify all Olmsted County, Minn. residents with incident venous thromboembolism and active cancer over the 18-year period, 1988-2005 (n = 374). One Olmsted County resident with active cancer without venous thromboembolism was matched to each case on age, sex, cancer diagnosis date, and duration of prior medical history. Subjects were followed forward in REP provider-linked billing data for standardized, inflation-adjusted direct medical costs from 1 year prior to index (venous thromboembolism event date or control-matched date) to the earliest of death, emigration from Olmsted County, or December 31, 2011, with censoring on the shortest follow-up to ensure a similar follow-up duration for each case-control pair. We used generalized linear modeling to predict costs for cases and controls and bootstrapping methods to assess uncertainty and significance of mean adjusted cost differences. Outpatient drug costs were not included in our estimates. Results Adjusted mean predicted costs were 1.9-fold higher for cases ($49,351) than for controls ($26,529) ( P < .001) from index to up to 5 years post index. Cost differences between cases and controls were greatest within the first 3 months (mean difference = $13,504) and remained significantly higher from 3 months to 5 years post index (mean difference = $12,939). Conclusions Venous thromboembolism-attributable costs among patients with active cancer contribute a substantial economic burden and are highest from index to 3 months, but may persist for up to 5 years.
The aim of this prospective study was to evaluate the incremental value of left atrial (LA) function for the prediction of risk for first atrial fibrillation (AF) or atrial flutter. Maximum and ...minimum LA volumes were quantitated by echocardiography in 574 adults (mean age 74 ± 6 years, 52% men) without a history or evidence of atrial arrhythmia. During a mean follow-up period of 1.9 ± 1.2 years, 30 subjects (5.2%) developed electrocardiographically confirmed AF or atrial flutter. Subjects with new AF or atrial flutter had lower LA reservoir function, as measured by total LA emptying fraction (38% vs 49%, p <0.0001) and higher maximum LA volumes (47 vs 40 ml/m2 , p = 0.005). An increase in age-adjusted risk for AF or atrial flutter was evident when the cohort was stratified according to medians of LA emptying fraction (≤49%: hazard ratio 6.5, p = 0.001) and LA volume (≥38 ml/m2 : hazard ratio 2.0, p = 0.07), with the risk being highest for subjects with concomitant LA emptying fractions ≤49% and LA volume ≥38 ml/m2 (hazard ratio 9.3, p = 0.003). LA emptying fraction (p = 0.002) was associated with risk for first AF or atrial flutter after adjusting for baseline clinical risk factors for AF or atrial flutter, left ventricular ejection fraction, diastolic function grade, and LA volume. In conclusion, reduced LA reservoir function markedly increases the propensity for first AF or atrial flutter, independent of LA volume, left ventricular function, and clinical risk factors.
Objectives This study sought to compare survival of patients with poorly compressible arteries (PCA) to those with a normal ankle-brachial index (ABI) and those with peripheral arterial disease ...(PAD). Background Limited data are available regarding survival in patients with PCA identified in the clinical setting by noninvasive lower extremity arterial evaluation. Methods We conducted a historical cohort study of consecutive patients who underwent outpatient, noninvasive lower extremity arterial evaluation at the Mayo Clinic, Rochester, Minnesota, from January 1998 through December 2007, and who were followed for a mean duration of 5.8 ± 3.1 years. An ABI 1.00 to 1.30 was considered normal, PAD was defined as a resting or post-exercise ABI ≤0.90, and PCA defined as an ABI ≥1.4 and/or an ankle systolic blood pressure >255 mm Hg. Patients were followed for all-cause mortality through September 30, 2009. Results Of 16,493 individuals (mean age 67.8 ± 13.0 years, 59% male); 29% had normal ABI, 54% had PAD, and 17% had PCA. During follow-up (mean duration 5.8 ± 3.1 years), 4,365 patients (26%) died. The percent alive at the end of the study period was 88%, 70%, and 60% for normal ABI, PAD, and PCA, respectively. After adjustment for age, sex, cardiovascular risk factors, comorbid conditions, and medication use, the hazard ratios (95% confidence intervals) of death associated with PCA were 2.0 (1.8 to 2.2) and 1.3 (1.2 to 1.4) compared with the normal ABI and PAD groups, respectively. Conclusions Patients identified by noninvasive vascular testing to have poorly compressible leg arteries have poor survival, worse than those with a normal ABI or those with PAD.
OBJECTIVE To determine the long-term outcome of computed tomographic (CT) quantification of coronary artery calcium (CAC) used as a triage tool for patients presenting with chest pain to an emergency ...department (ED). PATIENTS AND METHODS Patients (men aged 30-62 years and women aged 30-65 years) with chest pain and low-to-moderate probability of coronary artery disease underwent both conventional ED chest pain evaluation and CT CAC assessment prospectively. Patients' physicians were blinded to the CAC results. The results of the conventional evaluation were compared with CAC findings on CT, and the long-term outcome in patients undergoing CT CAC assessment was established. Primary end points (acute coronary syndrome, death, fatal or nonfatal non–ST-segment elevation myocardial infarction, fatal or nonfatal ST-segment elevation myocardial infarction) and secondary outcomes (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, coronary stenting, or a combination thereof) were obtained when the patient was dismissed from the ED or hospital and then at 30 days, 1 year, and 5 years. RESULTS Of the 263 study patients, 133 (51%) had a CAC score of zero. This absence of CAC correlated strongly with the likelihood of noncardiac chest pain. Among 133 patients with a CAC score of zero, only 1 (<1%) had cardiac chest pain. Conversely, of the 31 patients shown to have cardiac chest pain, 30 (97%) had evidence of CAC on CT. When a CAC cutoff score of 36 was used, as suggested by receiver operating characteristic analysis, sensitivity was 90%; specificity, 85%; positive predictive value, 44%; and negative predictive value, 99%. During long-term follow-up, patients without CAC experienced no cardiac events at 30 days, 1 year, and 5 years. CONCLUSION Findings suggest that CT CAC assessment is a powerful adjunct in chest pain evaluation for the population at low-to-intermediate risk. Absent or minimal CAC in this population makes cardiac chest pain extremely unlikely. The absence of CAC suggests an excellent long-term (5-year) prognosis, with no primary or secondary cardiac outcomes ocurring in study patients at 5-year follow-up.
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