Elisabeth J. Martens

Anxiety and Risk of Incident Coronary Heart Disease: A Meta-Analysis

OBJECTIVES The purpose of this study was to assess the association between anxiety and risk of coronary heart disease (CHD). BACKGROUND Less research has focused on the association of anxiety with incident CHD in contrast to other negative emotions, such as depression. METHODS A meta-analysis of references derived from PubMed, EMBASE, and PsycINFO (1980 to May 2009) was performed without language restrictions. End points were cardiac death, myocardial infarction (MI), and cardiac events. The authors selected prospective studies of (nonpsychiatric) cohorts of initially healthy persons in which anxiety was assessed at baseline. RESULTS Twenty studies reporting on incident CHD comprised 249,846 persons with a mean follow-up period of 11.2 years. Anxious persons were at risk of CHD (hazard ratio [HR] random: 1.26; 95% confidence interval [CI]: 1.15 to 1.38; p < 0.0001) and cardiac death (HR: 1.48; 95% CI: 1.14 to 1.92; p = 0.003), independent of demographic variables, biological risk factors, and health behaviors. There was a nonsignificant trend for an association between anxiety and nonfatal MI (HR: 1.43; 95% CI: 0.85 to 2.40; p = 0.180). Subgroup analyses did not show any significant differences regarding study characteristics, with significant associations for different types of anxiety, short- and long-term follow-up, and both men and women. CONCLUSIONS Anxiety seemed to be an independent risk factor for incident CHD and cardiac mortality. Future research should examine the association between anxiety and CHD with valid and reliable anxiety measures and focus on the mechanisms through which anxiety might affect CHD.

Quarterly Focus Issue: Prevention/OutcomesClinical Research: Cardiovascular RiskAnxiety and Risk of Incident Coronary Heart Disease: A Meta-Analysis

OBJECTIVES The purpose of this study was to assess the association between anxiety and risk of coronary heart disease (CHD). BACKGROUND Less research has focused on the association of anxiety with incident CHD in contrast to other negative emotions, such as depression. METHODS A meta-analysis of references derived from PubMed, EMBASE, and PsycINFO (1980 to May 2009) was performed without language restrictions. End points were cardiac death, myocardial infarction (MI), and cardiac events. The authors selected prospective studies of (nonpsychiatric) cohorts of initially healthy persons in which anxiety was assessed at baseline. RESULTS Twenty studies reporting on incident CHD comprised 249,846 persons with a mean follow-up period of 11.2 years. Anxious persons were at risk of CHD (hazard ratio [HR] random: 1.26; 95% confidence interval [CI]: 1.15 to 1.38; p < 0.0001) and cardiac death (HR: 1.48; 95% CI: 1.14 to 1.92; p = 0.003), independent of demographic variables, biological risk factors, and health behaviors. There was a nonsignificant trend for an association between anxiety and nonfatal MI (HR: 1.43; 95% CI: 0.85 to 2.40; p = 0.180). Subgroup analyses did not show any significant differences regarding study characteristics, with significant associations for different types of anxiety, short- and long-term follow-up, and both men and women. CONCLUSIONS Anxiety seemed to be an independent risk factor for incident CHD and cardiac mortality. Future research should examine the association between anxiety and CHD with valid and reliable anxiety measures and focus on the mechanisms through which anxiety might affect CHD.

Prognostic Association of Anxiety Post Myocardial Infarction With Mortality and New Cardiac Events: A Meta-Analysis

Objective: To assess the association of anxiety after myocardial infarction (MI) with cardiac prognosis. Methods: A meta-analysis of references derived from MEDLINE, EMBASE, and PSYCINFO (1975–March 2009) was performed without language restrictions. End point was cardiac outcome defined as all-cause mortality, cardiac mortality, and cardiac events. The authors selected prospective studies with at least 6 months follow-up, and anxiety had to be assessed within 3 months after MI with reliable and valid instruments. Results: Twelve papers met selection criteria. These studies described follow-up (on average, 2.6 years) of 5750 patients with MI. Anxious patients were at risk of adverse events (odds ratio (OR) fixed, 1.36; 95% confidence interval (CI), 1.18–1.56; p < .001). Anxiety was also specifically associated with all-cause mortality (OR fixed, 1.47; 95% CI, 1.02–2.13; p = .04), cardiac mortality (OR fixed, 1.23; 95% CI, 1.03–1.47; p = .02), and new cardiac events (OR fixed, 1.71; 95% CI, 1.31–2.23; p < .001). Conclusions: Post-MI anxiety is associated with a 36% increased risk of adverse cardiac outcomes in bivariate analyses. Because the existing literature is small and contains several limitations, more research is needed to evaluate the association of anxiety and prognosis in patients with MI and to assess the extent to which this association is independent of clinical variables, such as disease severity, and other psychological variables, especially depression. BMI = body mass index; CABG = coronary artery bypass graft; CHD = coronary heart disease; CI = confidence interval; CBAHF = Cognitive Behavioral Assessment Hospital Form; ENRICHD = Enhancing Recovery in Coronary Heart Disease Patients; FEM = fixed effects model; GAD = generalized anxiety disorder; HADS = Hospital Anxiety and Depression Scale; HR = hazard ratio; LVEF = left ventricular ejection fraction; MI = myocardial infarction; MIND-IT = Myocardial Infarction and Depression Intervention Trial; NA = not available; OR = odds ratio; REM = random effects model; STAI = State Trait Anxiety Inventory; STPI = State Trait Personality Inventory; UA = unstable angina.

Scared to Death? Generalized Anxiety Disorder and Cardiovascular Events in Patients With Stable Coronary Heart Disease: The Heart and Soul Study

CONTEXT Anxiety is common in patients with coronary heart disease (CHD), but studies examining the effect of anxiety on cardiovascular prognosis and the role of potential mediators have yielded inconsistent results. OBJECTIVES To evaluate the effect of generalized anxiety disorder (GAD) on subsequent cardiovascular events and the extent to which this association is explained by cardiac disease severity and potential behavioral or biological mediators. DESIGN Prospective cohort study (Heart and Soul Study). SETTING Participants were recruited between September 11, 2000, and December 20, 2002, from 12 outpatient clinics in the San Francisco Bay Area and were followed up until March 18, 2009. PARTICIPANTS One thousand fifteen outpatients with stable CHD followed up for a mean (SD) of 5.6 (1.8) years. MAIN OUTCOME MEASURES We determined the presence of GAD using the Diagnostic Interview Schedule. Proportional hazards models were used to evaluate the association of GAD with subsequent cardiovascular events and the extent to which this association was explained by potential confounders and mediators. RESULTS A total of 371 cardiovascular events occurred during 5711 person-years of follow-up. The age-adjusted annual rate of cardiovascular events was 9.6% in the 106 participants with GAD and 6.6% in the 909 participants without GAD (P = .03). After adjustment for demographic characteristics, comorbid conditions (including major depressive disorder), cardiac disease severity, and medication use, GAD remained associated with a 62% higher rate of cardiovascular events (hazard ratio, 1.62; 95% confidence interval, 1.11-2.37; P = .01). Additional adjustment for a variety of potential behavioral and biological mediators had little effect on this association (hazard ratio, 1.74; 95% confidence interval, 1.13-2.67; P = .01). CONCLUSIONS In outpatients with CHD, a robust association between GAD and cardiovascular events was found that could not be explained by disease severity, health behaviors, or biological mediators. How GAD leads to poor cardiovascular outcomes deserves further study.

Preoperative Hemoglobin Level as a Predictor of Survival After Coronary Artery Bypass Grafting A Comparison With the Matched General Population

Background— The predictive value of the preoperative hemoglobin value after coronary artery bypass grafting (CABG) has not been well established. We studied how the preoperative hemoglobin level affects the survival of patients after CABG. Late mortality was compared with that of a general population. Methods and Results— Early and late mortality of all consecutive patients undergoing isolated CABG between January 1998 and December 2007 were determined. Patients were classified into 4 groups stratified by preoperative hemoglobin level. The cutoff point for anemia was 13 g/dL for men and 12 g/dL for women. Expected survival of a matched general Dutch population cohort was obtained from the database of the Dutch Central Bureau for Statistics. After the exclusion of 122 patients who were lost to follow-up and 481 patients with missing preoperative hemoglobin levels, complete data were obtained in 10 025 patients. Multivariate logistic regression analyses revealed anemia to be an independent risk factor for higher early mortality. Cox regression analyses revealed low hemoglobin level, both as a continuous variable and as a dichotomous variable (anemia), to be a predictor of higher late mortality. Compared with expected survival, patients with the lowest preoperative hemoglobin levels had a worse outcome, whereas patients with the highest hemoglobin levels had a better outcome. Conclusions— A lower preoperative hemoglobin level is an independent predictor of late mortality in patients undergoing CABG, whereas anemia is a risk factor for early and late mortality. Compared with the general population, anemic patients had worse survival than expected, whereas nonanemic patients had better survival than expected.

Differential associations between specific depressive symptoms and cardiovascular prognosis in patients with stable coronary heart disease.

OBJECTIVES The purpose of this research was to evaluate the relationship between cognitive and somatic depressive symptoms and cardiovascular prognosis. BACKGROUND Depression in patients with stable coronary heart disease (CHD) is associated with poor cardiac prognosis. Whether certain depressive symptoms are more cardiotoxic than others is unknown. METHODS In the Heart and Soul Study, 1,019 patients with stable CHD were assessed using the Patient Health Questionnaire to determine the presence of the 9 depressive symptoms included in the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. The mean age of the patients was 67 years, and 82% were men. A comparison was made on a new cardiovascular event (myocardial infarction, stroke, transient ischemic attack, or congestive heart failure) or death (mean follow-up duration 6.1 +/- 2.0 years) on the basis of cognitive and somatic sum scores and for patients with or without each of those specific depressive symptoms. Demographic characteristics, cardiac risk factors, and cardiac medications were controlled for. RESULTS After adjustment for demographic data and cardiac risk factors, each somatic symptom was associated with 14% greater risk for events (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.05 to 1.24; p = 0.002). Fatigue (HR: 1.34; 95% CI: 1.07 to 1.67; p = 0.01), appetite problems (HR: 1.46; 95% CI: 1.12 to 1.91; p = 0.005), and sleeping difficulties (HR: 1.26; 95% CI: 1.00 to 1.58; p = 0.05) were most strongly predictive of cardiovascular events. In contrast, cognitive symptoms (HR: 1.08; 95% CI: 0.99 to 1.17; p = 0.09) were not significantly associated with cardiovascular events. CONCLUSIONS In patients with stable CHD, somatic symptoms of depression were more strongly predictive of cardiovascular events than cognitive symptoms, although the CIs surrounding these estimates had substantial overlap. These findings are highly consistent with those of previous studies. Further research is needed to understand the pathophysiological processes by which somatic depressive symptoms contribute to prognosis in patients with CHD.

Transfusion of red blood cells: The impact on short-term and long-term survival after coronary artery bypass grafting, a ten-year follow-up

Transfusion of red blood cells (RBC) and other blood products in patients undergoing coronary artery bypass grafting (CABG) is associated with increased mortality and morbidity. We retrospectively analyzed data of patients who underwent an isolated coronary bypass graft operation between January 1998 and December 2007. Mean follow-up was 1696+/-1026 days, with exclusion of 122 patients lost to follow-up and 80 patients who received 10 units of RBC. Of the remaining patients, 8001 (76.7%) received no RBC, 1621 (15.2%) received 1-2 units of RBC, 593 (5.7%) received 3-5 units and 220 (2.1%) received 6-10 units. The number of transfused RBC was a predictor for early but not for late mortality. When compared to expected survival, survival of patients not receiving any blood product was better, while survival of patients receiving >3 units of RBC was worse. Transfusion of RBC is an independent, dose-dependent risk factor for early mortality after revascularization. Compared to expected survival, receiving no RBC improves patient long-term survival, whereas receiving three or more units of RBC significantly decreases patient survival.

Correlates of osteoporosis in chronic obstructive pulmonary disease: An underestimated systemic component.

RATIONALE Chronic obstructive pulmonary disease (COPD) patients are at increased risk of osteoporosis. Osteoporosis is under diagnosed and under treated in these patients and the underlying mechanisms remain unclear. To date, screening recommendations for osteoporosis in COPD patients are not available. OBJECTIVES To examine the prevalence of drug treatment of bone abnormalities as well as the clinical determinants of osteoporosis in COPD. METHODS COPD patients (n=554) consecutively entering pulmonary rehabilitation were included in this cross-sectional study. Medical history, current medication use, smoking status, lung function, bone mineral density, body composition and other clinical characteristics were assessed before entering pulmonary rehabilitation. Univariate- and multivariate multinomial logistic regression analyses were used to determine correlates of osteoporosis. MAIN RESULTS Twenty-one percent of patients had osteoporosis and 41% had osteopenia. Osteoporosis was pharmacologically under treated (82% of osteoporotic patients were not receiving bone medication). Independent predictors of osteoporosis were cachexia (OR: 12.1; 95%CI: 4.5-32.7; p<0.001), age between 55 and 65 years (OR: 6.0; 95%CI: 2.2-16.3; p<0.001) and over 65 years (OR: 11.7; 95%CI: 4.1-33.1; p=<0.001). Overweight (OR: 0.1; 95%CI: 0.05-0.4; p=0.001) and obesity (OR: 0.78; 95%CI: 0.02-0.4; p=0.002) showed a substantial protective effect. CONCLUSIONS The majority of COPD patients with osteoporosis entering pulmonary rehabilitation did not receive pharmacological treatment for osteoporosis. Cachectic COPD patients should be screened for osteoporosis, especially when over 55 years of age.

Depression and anxiety as predictors of heart rate variability after myocardial infarction

BACKGROUND Reduced heart rate variability (HRV) is a prognostic factor for cardiac mortality. Both depression and anxiety have been associated with increased risk for mortality in cardiac patients. Low HRV may act as an intermediary in this association. The present study examined to what extent depression and anxiety differently predict 24-h HRV indices recorded post-myocardial infarction (MI). METHOD Ninety-three patients were recruited during hospitalization for MI and assessed on self-reported symptoms of depression and anxiety. Two months post-MI, patients were assessed on clinical diagnoses of lifetime depressive and anxiety disorder. Adequate 24-h ambulatory electrocardiography data were obtained from 82 patients on average 78 days post-MI. RESULTS In unadjusted analyses, lifetime diagnoses of major depressive disorder was predictive of lower SDNN [standard deviation of all normal-to-normal (NN) intervals; beta=-0.26, p=0.022] and SDANN (standard deviation of all 5-min mean NN intervals; beta=0.25, p=0.023), and lifetime anxiety disorder of lower RMSSD (root mean square of successive differences; beta=-0.23, p=0.039). Depression and anxiety symptoms did not significantly predict HRV. After adjustment for age, sex, cardiac history and multi-vessel disease, lifetime depressive disorder was no longer predictive of HRV. Lifetime anxiety disorder predicted reduced high-frequency spectral power (beta=-0.22, p=0.039) and RMSSD (beta=-0.25, p=0.019), even after additional adjustment of anxiety symptoms. CONCLUSIONS Clinical anxiety, but not depression, negatively influenced parasympathetic modulation of heart rate in post-MI patients. These findings elucidate the physiological mechanisms underlying anxiety as a risk factor for adverse outcomes, but also raise questions about the potential role of HRV as an intermediary between depression and post-MI prognosis.

Postoperative blood loss in patients undergoing coronary artery bypass surgery after preoperative treatment with clopidogrel. A prospective randomised controlled study

OBJECTIVE The optimal timing for discontinuation of clopidogrel before surgery remains under debate. The purpose of this study is to determine the effect of preoperative clopidogrel administration on postoperative blood loss and the total requirements of homologous blood products after coronary artery bypass grafting (CABG). We also evaluated the perioperative complications. METHODS Consecutive patients (n=130) undergoing elective CABG were recruited and randomised between 2006 and 2007. In 38 patients (group 1), treatment with clopidogrel was discontinued 5 days prior to surgery, in 40 patients (group 2) 3 days before surgery and in 40 other patients (group 3) clopidogrel was stopped on the day of surgery. RESULTS Significantly more postoperative blood loss was observed in group 3 compared to group 1 (929+/-472 ml vs 664+/-312 ml; p=0.009). Other group comparisons were not significant. Blood loss after 12 h and at drain removal was also significantly higher in group 3. Patients in group 3 also had higher total requirements of homologous blood products (p=0.046) and a significantly higher need for fresh frozen plasma (FFP) transfusion (p=0.034). Univariable regression analyses revealed that continuing clopidogrel till the day of surgery (group 3) was predictive for postoperative blood loss (beta=0.289; p=0.007) and the total requirements of homologous blood products after surgery (beta=0.280; p=0.008). These effects remained the same in multivariable analyses. CONCLUSIONS Continuation of clopidogrel until the day of surgery induces significantly more postoperative blood loss and increases significantly the total requirements of homologous blood products and FFP transfusion after surgery. The blood loss and the use of blood products in the group that stopped at 3 days preoperatively were similar to that of the group that stopped at 5 days preoperatively.