Viola Vaccarino

A Common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction

The global endemic of cardiovascular diseases calls for improved risk assessment and treatment. Here, we describe an association between myocardial infarction (MI) and a common sequence variant on chromosome 9p21. This study included a total of 4587 cases and 12,767 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with the disease with high significance. Approximately 21% of individuals in the population are homozygous for this variant, and their estimated risk of suffering myocardial infarction is 1.64 times as great as that of noncarriers. The corresponding risk is 2.02 times as great for early-onset cases. The population attributable risk is 21% for MI in general and 31% for early-onset cases.

Sex-Based Differences in Early Mortality after Myocardial Infarction

Background There is conflicting information about whether short-term mortality after myocardial infarction is higher among women than among men after adjustment for age and other prognostic factors. We hypothesized that younger, but not older, women have higher mortality rates during hospitalization than their male peers. Methods We analyzed data on 384,878 patients (155,565 women and 229,313 men) who were 30 to 89 years of age and who had been enrolled in the National Registry of Myocardial Infarction 2 between June 1994 and January 1998. Patients who had been transferred from or to other hospitals were excluded. Results The overall mortality rate during hospitalization was 16.7 percent among the women and 11.5 percent among the men. Sex-based differences in the rates varied according to age. Among patients less than 50 years of age, the mortality rate for the women was more than twice that for the men. The difference in the rates decreased with increasing age and was no longer significant after the age ...

The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 × 10−12) and intracranial aneurysm (OR = 1.29, P = 2.5 × 10−6), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 × 10−14, 5.4 × 10−10, 8.6 × 10−17, 1.2 × 10−10 and 6.5 × 10−19, respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 × 10−12) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 × 10−6, 2.2 × 10−5 and 2.4 × 10−4, respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 × 10−8) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

Randomized trial of an education and support intervention to prevent readmission of patients with heart failure

OBJECTIVES We determined the effect of a targeted education and support intervention on the rate of readmission or death and hospital costs in patients with heart failure (HF). BACKGROUND Disease management programs for patients with HF including medical components may reduce readmissions by 40% or more, but the value of an intervention focused on education and support is not known. METHODS We conducted a prospective, randomized trial of a formal education and support intervention on one-year readmission or mortality and costs of care for patients hospitalized with HF. RESULTS Among the 88 patients (44 intervention and 44 control) in the study, 25 patients (56.8%) in the intervention group and 36 patients (81.8%) in the control group had at least one readmission or died during one-year follow-up (relative risk = 0.69, 95% confidence interval [CI]: 0.52, 0.92; p = 0.01). The intervention was associated with a 39% decrease in the total number of readmissions (intervention group: 49 readmissions; control group: 80 readmissions, p = 0.06). After adjusting for clinical and demographic characteristics, the intervention group had a significantly lower risk of readmission compared with the control group (hazard ratio = 0.56, 95% CI: 0.32, 0.96; p = 0.03) and hospital readmission costs of

Depressive symptoms and risk of functional decline and death in patients with heart failure

7,515 less per patient. CONCLUSIONS A formal education and support intervention substantially reduced adverse clinical outcomes and costs for patients with HF.

Predictors of readmission among elderly survivors of admission with heart failure

OBJECTIVES We sought to examine whether depressive symptoms are associated with poorer prognosis in patients with heart failure. BACKGROUND Depression is an established risk factor for poor outcome in patients with coronary heart disease (CHD). Little is known of its role in patients with heart failure. METHODS We prospectively followed 391 patients > or =50 years of age who met criteria for decompensated heart failure on hospital admission. The outcome of the study was death or decline in activities of daily living (ADL) at six months, relative to baseline. Depressive symptoms were measured at baseline by means of the Geriatric Depression Scale, Short-Form, with 6 to 7 symptoms, 8 to 10 symptoms and > or =11 symptoms indicating mild, moderate and severe levels of depressive symptoms, respectively. RESULTS There was a strong and graded association between the severity of depressive symptoms at baseline and the rate of the combined end point of either functional decline or death at six months. After adjustment for demographic factors, medical history, baseline functional status and clinical severity, patients with > or =11 depressive symptoms, compared with those with <6 depressive symptoms, had an 82% higher risk of either functional decline or death, whereas the intermediate levels of depressive symptoms showed intermediate risk (p = 0.003 for trend). A similar graded association was found for functional decline and death separately; however, after multivariate analysis, the association with mortality was less strong and no longer statistically significant. CONCLUSIONS An increasing number of depressive symptoms is a negative prognostic factor for patients with heart failure, just as it is for patients with CHD.

Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health--National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation.

BACKGROUND Readmission rates for patients discharged with heart failure approach 50% within 6 months. Identifying factors to predict risk of readmission in these patients could help clinicians focus resource-intensive disease management efforts on the high-risk patients. METHODS The study sample included patients 65 years of age or older with a principal discharge diagnosis of heart failure who were admitted to 18 Connecticut hospitals in 1994 and 1995. We obtained patient and clinical data from medical record review. We determined outcomes within 6 months after discharge, including all-cause readmission, heart failure-related readmission, and death, from the Medicare administrative database. We evaluated 2176 patients, including 1129 in the derivation cohort and 1047 in the validation cohort. RESULTS Of 32 patient and clinical factors examined, 4 were found to be significantly associated with readmission in a multivariate model. They were prior admission within 1 year, prior heart failure, diabetes, and creatinine level >2.5 mg/dL at discharge. The event rates according to number of risk predictors were similar in the derivation and the validation sets for all outcomes. In the validation cohort, rates for all-cause readmission and combined readmission or death were 26% and 31% in patients with no risk predictors, 48% and 54% in patients with 1 or 2 risk predictors, and 59% and 65% in patients with 3 or all risk predictors. CONCLUSIONS Few patient and clinical factors predict readmission within 6 months after discharge in elderly patients with heart failure. Although we were unable to identify a group of patients at very low risk, a group of high-risk patients were identified for whom resource-intensive interventions designed to improve outcomes may be justified.

Depression as a Risk Factor for Poor Prognosis Among Patients With Acute Coronary Syndrome: Systematic Review and Recommendations A Scientific Statement From the American Heart Association

BACKGROUND Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. OBJECTIVE The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Womens Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. METHODS A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (> or = 701 pg/ml), testosterone (> or = 30.9 ng/dl), or free testosterone (> or = 4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55). RESULTS Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. CONCLUSION Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.

A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction

Background— Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. Methods and Results— Writing group members were approved by the American Heart Association’s Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. Conclusions— Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.