Roxanne Pelletier

Association between clinical depression and endothelial function measured by forearm hyperemic reactivity.

Objective: To assess associations between clinically significant depression (major depressive disorder [MDD] and minor depressive disorder [MiDD]) and endothelial function (EF), via forearm hyperemic reactivity (FHR), in patients referred for myocardial perfusion imaging. Studies have linked MDD to impaired EF, an early marker of coronary heart disease (CHD) and risk factor for cardiac events, in healthy, noncardiac patients, although no studies have assessed the MDD-EF association in patients with or at risk for CHD. Methods: Depression was assessed, using the Primary Care Evaluation of Mental Disorders structured interview in 323 patients (n = 242 men; mean age = 59 years) with or at risk for CHD. FHR was assessed, using a dynamic nuclear imaging technique that measures the dilatory capability of the brachial artery during hyperemic challenge. The relative uptake ratio (RUR) of blood flow between hyperemic and nonhyperemic arms was used to measure FHR. Results: Patients with MDD and MiDD had lower RURs (mean values = 3.31 and 3.34, respectively), indicating poorer EF than patients without depression (mean = 4.27) (F = 5.19, p < .01), irrespective of CHD status. All results were adjusted for covariates including sociodemographic, medical, biochemical, and physiological variables. Conclusions: Patients with clinical levels of depression had worse FHR than patients without depression, irrespective of CHD status and after adjusting for covariates. Data extend previous findings, suggesting that the link between clinical depression and worse CHD outcomes may be mediated by EF. BDI = Beck Depression Inventory; CHD = coronary heart disease; CRP = C-reactive protein; DSM = Diagnostic and Statistical Manual; EF = endothelial function; FHR = forearm hyperemic reactivity; FMD = flow-mediated dilatation; HPA = hypothalamic-pituitary-adrenal; MDD = major depressive disorder; MiDD = minor depressive disorder; MI = myocardial infarction; NO = nitric oxide; PRIME-MD = Primary Care Evaluation of Mental Disorders; RUR = relative uptake ratio; SCID = Structured Clinical Interview for DSM; SPECT = single photon emission computed tomography.

Sex- and Gender-Related Risk Factor Burden in Patients With Premature Acute Coronary Syndrome

BACKGROUND Few contemporary data exist on traditional (TRF) and non-TRF (NTRF) burden in patients with premature acute coronary syndrome (ACS). METHODS Prevalence of TRFs and NTRFs were measured in 1015 young (55 years old or younger) ACS patients recruited from 26 centres in Canada, the United States, and Switzerland. Risk factors were compared across sex and family history categories, and against a sample of the general Canadian population based on the 2000-2001 Canadian Community Health Survey. The 10- and 30-year risks of cardiovascular disease (CVD) were estimated using Framingham Risk Scores. RESULTS Risk factors were more prevalent in premature ACS patients compared with the general population. Young women with a family history of coronary artery disease showed the greatest risk factor burden including TRFs of hypertension (67%), dyslipidemia (67%), obesity (53%), smoking (42%), and diabetes (33%), and NTRFs of anxiety (55%), low household income (44%), and depression (37%). The estimated median 10-year risk of CVD was 7% (interquartile range [IQR], 3%-9%) in women and 13% (IQR, 7%-17%) in men, whereas the 30-year risk of CVD was 36% (IQR, 22%-49%) in women and 44% (IQR, 31%-57%) in men. CONCLUSIONS Patients with premature ACS, especially women with a positive family history, are characterized by a very high risk factor burden that is poorly captured by 10-year risk estimates but better captured by 30-year estimates. Consideration of NTRFs and use of 30-year risk estimates might better estimate risk in young individuals and improve the prevention of premature ACS.

A composite measure of gender and its association with risk factors in patients with premature acute coronary syndrome.

Objective To create a gender index by using principal component analyses (PCA) and logistic regression, and to determine the association between gender, sex, and cardiovascular risk factors among patients with premature acute coronary syndrome (ACS). Methods GENESIS-PRAXY is a cohort study including ACS patients aged 55 years or below, and with ACS recruited between 2009 and 2013 from 26 centres across Canada, the United States, and Switzerland. A sample of 1075 patients was used for this study. Psychosocial variables assumed to differ between sexes (i.e., gender related) were included in PCA. Variables identified on retained components were included in logistic regressions where coefficient estimates of variables associated with sex were used to calculate a gender score. Cardiovascular risk factors were assessed using self-report and chart review data. Results After the inclusion of 26 psychosocial variables in PCA, we identified 17 variables within retained components; 7 of which were associated with sex in logistic regression. The gender distribution revealed that half of women had a more androgyne or masculine gender score, and 16% of men exhibited a more feminine gender score. In univariable analyses, feminine gender scores and female sex were associated with hypertension, diabetes, family history of cardiovascular disease (only gender), and depressive/anxious symptoms. In multivariable models including both gender score and sex, feminine gender score but not female sex was associated with the presence of risk factors. Conclusions Sex and gender are distinct constructs, and the derived gender index offers a current and pragmatic option to measure gender within ACS populations. Our results further suggest that traditional sex differences in cardiovascular disease risk factors may be partly explained by patients gender-related characteristics.

Health‐Related Quality of Life in Premature Acute Coronary Syndrome: Does Patient Sex or Gender Really Matter?

Background Limited data exist as to the relative contribution of sex and gender on health‐related quality of life (HRQL) among patients with acute coronary syndrome (ACS). This study aims to evaluate the effect of sex and gender‐related variables on long‐term HRQL among young adults with ACS. Methods and Results GENESIS‐PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond‐Premature Acute Coronary SYndrome) is a multicenter, prospective cohort study (January 2009 to August 2013) of adults aged 18 to 55 years, hospitalized with ACS. HRQL was measured at baseline, 1, 6, and 12 months using the Short Form‐12 and Seattle Angina Questionnaire (SAQ) among 1213 patients. Median age was 49 years. Women reported worse HRQL than men over time post‐ACS, both in terms of physical and mental functioning. Gender‐related factors were more likely to be predictors of HRQL than sex. Femininity score, social support, and housework responsibility were the most common gender‐related predictors of HRQL at 12 months. We observed an interaction between female sex and social support (β=0.44 [95% confidence interval, 0.01, 0.88]; P=0.047) for the physical limitation subscale of the SAQ. Conclusions Young women with ACS report significantly poorer HRQL than young men. Gender appears to be more important than sex in predicting long‐term HRQL post‐ACS. Specific gender‐related factors, such as social support, may be amenable to interventions and could improve the HRQL of patients with premature ACS.

The effect of major depression on postexercise cardiovascular recovery.

Major depressive disorder (MDD) is associated with increased cardiovascular (CV) mortality. Dysfunctional autonomic control of the CV system may represent a mechanism explaining this relationship. Poor CV recovery after exercise, indicative of dysfunctional autonomic control of the CV system, predicts CV events and death. This is the first study to examine the association between MDD and postexercise CV recovery. Some 886 patients underwent exercise stress tests. Heart rate (HR), systolic blood pressure, and diastolic blood pressure were measured at rest, peak exercise, 1 min, and 5 min after exercise. Patients with MDD had slower HR recovery (p=.026) 1 min after exercise than non-MDD patients. No other effects of MDD were found. MDD is accompanied by a dysregulation in autonomic control of exercise-related CV recovery, suggesting that depressed individuals have a slow parasympathetic recovery from exercise.

The impact of acute and chronic exercise on thrombosis in cardiovascular disease

There is now a large and impressive literature showing that people who engage in chronic aerobic exercise or who have better cardiovascular fitness levels, tend to live longer and have lower levels of cardiovascular disease (CVD). However, there is a paradox, as acute aerobic exercise has been associated with an increased risk of CVD events. There are now a number of review articles suggesting that the differential benefits of chronic, relative to acute, exercise might be due to thrombotic changes, though the majority of this data is derived from healthy individuals. However, acute exercise is of greater concern and chronic exercise of greater benefit to patient populations. In addition, these higher risk groups tend to present with more complex profiles, e.g. they may be taking medications that influence thrombotic pathways. As such, the current review has focused on newer information relating to exercise, physical activity and thrombosis in patient populations, and highlights some of the growing areas in the field. For example, the impact of warm-up exercise, the interaction of medications, and issues surrounding the optimal volume and intensity of exercise.

Depression and disease severity in patients with premature acute coronary syndrome.

OBJECTIVES The association between depression and cardiovascular disease severity in younger patients has not been assessed, and sex differences are unknown. We assessed whether major depression and depressive symptoms were associated with worse cardiovascular disease severity in patients with premature acute coronary syndrome, and we assessed sex differences in these relationships. METHODS We enrolled 1023 patients (aged ≤ 55 years) hospitalized with acute coronary syndrome from 26 centers in Canada, the United States, and Switzerland, through the GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary Syndrome study. Left ventricular ejection fraction, Killip class, cardiac troponin I, and Global Registry of Acute Coronary Events score data were collected through chart review. RESULTS The sample comprised 248 patients with major depression and 302 women. In univariate analyses, major depression was associated with a lower likelihood of having an abnormal left ventricular ejection fraction (odds ratio, 0.70; 95% confidence interval, 0.51-0.97; P = .03) and lower troponin I levels (estimate, -4.04; 95% confidence interval, -8.01 to -0.06; P = .05). After adjustment for sociodemographic and clinical characteristics, neither major depression nor depressive symptoms were associated with disease severity indices, and there were no sex differences. CONCLUSION The increased risk of adverse events in depressed patients with premature acute coronary syndrome is not explained by disease severity.

Premature cardiovascular disease following a history of hypertensive disorder of pregnancy

BACKGROUND Following an episode of hypertensive disorder of pregnancy (HDP) women have an increased risk of cardiovascular disease over their lifetime. At the time of acute coronary syndrome we compared clinical information between women with and without a history of hypertension in pregnancy to gain further insight into the pathophysiology of cardiovascular disease in this population. METHODS GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-PRemature Acute Coronary SYdrome) is a prospective multicenter study, with recruitment between January 2009 and April 2013, including 242 parous women with premature acute coronary syndrome. RESULTS The median age was 50years (IQR 6) and HDP was common; 43 (17.8%) women had prior gestational hypertension, 33 (13.6%) preeclampsia and 166 (68.6%) a prior normotensive pregnancy. Women with a history of HDP commonly had chronic hypertension and diabetes and those presenting with ST-elevation myocardial infarction were more likely to have a history of preeclampsia (aOR 3.12, 95% CI 1.22-8.01) than were women with prior normotensive pregnancies. Neither gestational hypertension (aOR 1.40, 95% CI 0.60-3.26) nor preeclampsia (aOR 0.63, 95% CI 0.23-1.74) was associated with a higher composite risk of three-vessel, left main or proximal left anterior descending coronary disease. CONCLUSION In this study of women with premature cardiovascular disease, ST-elevation myocardial infarction was associated with a history of preeclampsia possibly because of persistent endothelial dysfunction. High-risk coronary lesions on angiography did not appear to have an association with preeclampsia or gestational hypertension despite a high burden of traditional risk factors.

Relative associations between depression and anxiety on adverse cardiovascular events: does a history of coronary artery disease matter? A prospective observational study

Objectives To assess whether depression and anxiety increase the risk of mortality and major adverse cardiovascular events (MACE), among patients with and without coronary artery disease (CAD). Design and setting, and patients DECADE (Depression Effects on Coronary Artery Disease Events) is a prospective observational study of 2390 patients referred at the Montreal Heart Institute. Patients were followed for 8.8 years, between 1998 and 2009. Depression and anxiety were assessed using a psychiatric interview (Primary Care Evaluation of Mental Disorders, PRIME-MD). Outcomes data were obtained from Quebec provincial databases. Main outcome measures All-cause mortality and MACE. Results After adjustment for covariates, patients with depression were at increased risks of all-cause mortality (relative risk (RR)=2.84; 95% CI 1.25 to 6.49) compared with patients without depression. Anxiety was not associated with increased mortality risks (RR=0.86; 95% CI 0.31 to 2.36). When patients were stratified according to CAD status, depression increased the risk of mortality among patients with no CAD (RR=4.39; 95% CI 1.12 to 17.21), but not among patients with CAD (RR=2.32; 95% CI 0.78 to 6.88). Neither depression nor anxiety was associated with MACE among patients with or without CAD. Conclusions and relevance Depression, but not anxiety, was an independent risk factor for all-cause mortality in patients without CAD. The present study contributes to a better understanding of the relative and unique role of depression versus anxiety among patients with versus without CAD.

The role of mood disorders in exercise-induced cardiovascular reactivity.

Objective: Increased cardiovascular (CV) reactivity has been associated with worse CV prognosis. Though mood disorders (MDs) have been associated with increased CV reactivity during behavioral stressors, the extent to which MDs and their interaction with coronary heart disease (CHD) influences exercise-induced CV reactivity has not been evaluated. Methods: Five hundred twenty-six patients underwent nuclear exercise stress testing. Cardiovascular parameters were assessed at rest, every 2 minutes during exercise, and at peak exercise. MDs were measured using a structured psychiatric interview, the Primary Care Evaluation of Mental Disorders, and CHD was defined as having a history of myocardial infarction, revascularization, heart failure, and/or cerebrovascular event. Results: CHD patients exhibited lower peak exercise heart rate (F = 9.40, p = .002) compared with patients without CHD. Submaximal data showed that patients with CHD had a slower rate of increase of heart rate (F = 4.29, p = .04) and diastolic blood pressure (F = 3.27, p = .04). There was an interaction of CHD and MDs, indicating that in patients with CHD, the rate of submaximal increase in systolic blood pressure (F = 3.08, p = .047) and rate-pressure product (F = 5.13, p = .006) was greater in patients with a MD compared with those without a MD. These differences were not observed in patients with no CHD. No other main or interaction effects of MDs and CHD were observed. Conclusion: Though MDs alone do not seem to be associated with higher levels of stress CV reactivity, their combination with CHD leads to increased submaximal exercise-induced CV reactivity. Prospective studies are needed to explore the causal relationship between these variables. CV = cardiovascular; HR = heart rate; CHD = coronary heart disease; SBP = systolic blood pressure; MDs = mood disorders; DBP = diastolic blood pressure; RPP = rate-pressure product; BP = blood pressure; SPECT = single photon emission computed tomography; SES = socioeconomic status; BRS = baroreceptor sensitivity; BMI = body mass index; MI = myocardial infarction; MOSMI = Mechanisms and Longitudinal Outcomes of Silent Myocardial Ischemia.