Indexes of aortic wave reflection are not augmented in estrogen-deficient physically active premenopausal women.

BACKGROUND: Hypoestrogenemia due to menopause is associated with increased cardiovascular disease risk, in part due to elevated indexes of aortic wave reflection (AWRI) and central (aortic) blood pressure. We sought to investigate whether AWRI and central blood pressure are also augmented in hypoestrogenic exercise-trained premenopausal women with functional hypothalamic amenorrhea (ExFHA). METHODS: In age- (pooled mean ± SEM, 24 ± 1 years), BMI- (21 ± 1 kg/m2 ), and cardiorespiratory fitness-matched (45 ± 2 ml/kg/min) eumenorrheic ovulatory (ExOv; n = 11) and ExFHA women (n = 10), we assessed aortic blood pressure and waveform characteristics (augmentation index and wave reflection amplitude) obtained from radial pressure waves (applanation tonometry). Doppler ultrasound determined cardiac output (CO) and total peripheral resistance (TPR). Measures were recorded before and 1 hour after 45 minutes of moderate intensity exercise to determine the influence of exercise-induced increases in nitric oxide. RESULTS: Pre-exercise, AIx75, central systolic BP (SBPc), and CO were lower (P < .05) and TPR higher (P < .05) in ExFHA. Post-exercise, AIx75 was unchanged (P > .05) in ExFHA but was lowered (P < .05) in ExOv. Both groups demonstrated increased CO, and lowered SBPc and TPR, yet TPR remained higher (P < .05), and CO and SBPc lower (P < .05) in ExFHA. CONCLUSIONS: Despite hypoestrogenemia, functional compliance of the central arteries and central BP is not augmented, yet TPR is higher, in ExFHA versus ExOv. An acute bout of dynamic exercise did not alter AIx75 in ExFHA, suggesting blunted vascular responsiveness to exercise-induced increases in nitric oxide, possibly due to augmented vascular tone. These findings have relevance in understanding the vascular consequences of hypoestrogenemia during the premenopausal years.

Augmented vagal heart rate modulation in active hypoestrogenic pre-menopausal women with functional hypothalamic amenorrhoea.

Compared with eumenorrhoeic women, exercise-trained women with functional hypothalamic amenorrhoea (ExFHA) exhibit low heart rates (HRs) and absent reflex renin-angiotensin-system activation and augmentation of their muscle sympathetic nerve response to orthostatic stress. To test the hypothesis that their autonomic HR modulation is altered concurrently, three age-matched (pooled mean, 24 ± 1 years; mean ± S.E.M.) groups of women were studied: active with either FHA (ExFHA; n=11) or eumenorrhoeic cycles (ExOv; n=17) and sedentary with eumenorrhoeic cycles (SedOv; n=17). Blood pressure (BP), HR and HR variability (HRV) in the frequency domain were determined during both supine rest and graded lower body negative pressure (LBNP; -10, -20 and -40 mmHg). Very low (VLF), low (LF) and high (HF) frequency power spectra (ms(2)) were determined and, owing to skewness, log10-transformed. LF/HF ratio and total power (VLF + LF + HF) were calculated. At baseline, HR and systolic BP (SBP) were lower (P<0.05) and HF and total power were higher (P<0.05) in ExFHA than in eumenorrhoeic women. In all groups, LBNP decreased (P<0.05) SBP, HF and total power and increased (P<0.05) HR and LF/HF ratio. However, HF and total power remained higher (P<0.05) and HR, SBP and LF/HF ratio remained lower (P<0.05) in ExFHA than in eumenorrhoeic women, in whom measures did not differ (P>0.05). At each stage, HR correlated inversely (P<0.05) with HF. In conclusion, ExFHA women demonstrate augmented vagal yet unchanged sympathetic HR modulation, both at rest and during orthostatic stress. Although the role of oestrogen deficiency is unclear, these findings are in contrast with studies reporting decreased HRV in hypoestrogenic post-menopausal women.

Estrogen status and the renin angiotensin aldosterone system.

The renin-angiotensin-aldosterone system (RAAS) is integrally involved in multiple cardiovascular physiological processes including arterial blood pressure (BP) regulation. Over activity of the RAAS has been implicated in the pathogenesis of a number of cardiovascular disease entities, including hypertension. Several lines of evidence suggest estrogen favorably modulates the RAAS. Conversely, estrogen deficiency due to menopause may contribute to over activity of the RAAS. Of importance, estrogen deficiency in women is not exclusive to the postmenopausal period. Functional hypothalamic amenorrhea is a reversible cause of premenopausal hypoestrogenemia. In contrast to postmenopausal women (PMW), premenopausal women with exercise-associated functional hypothalamic amenorrhea demonstrate decreased, not increased, resting BP compared with their estrogen-replete eumenorrheic counterpart. In this review we briefly examine the effects of estrogen status on the RAAS and present the hypothesis that the RAAS is altered in physically active women with functional hypothalamic amenorrhea.

The relation between total joint arthroplasty and risk for serious cardiovascular events in patients with moderate-severe osteoarthritis: propensity score matched landmark analysis.

STUDY QUESTION: What are the rates of serious cardiovascular events in those who undergo primary total joint arthroplasty (TJA) compared with those who do not within three years of initial assessment? SUMMARY ANSWER: Undergoing elective primary TJA within three years of initial assessment was associated with a significant 12.4% absolute reduction in subsequent risk of serious cardiovascular events. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Osteoarthritis is associated with increased mortality, particularly secondary to cardiovascular disease, with the risk for mortality proportional to the degree of disability secondary to the arthritis. This study suggests that management of hip or knee osteoarthritis with arthroplasty decreases the risk for subsequent serious cardiovascular events.

State-of-the-Art Review for the American Journal of Hypertension Cardio-Rheumatology insights into hypertension: Intersection of inflammation, arteries, and heart.

There is an increased prevalence of atherosclerotic cardiovascular disease (ASCVD) in patients with inflammatory rheumatic diseases (IRD) including rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, and systemic sclerosis. The mechanism for development of ASCVD in these conditions has been linked not only to a higher prevalence and undertreatment of traditional cardiovascular (CV) risk factors, but importantly to chronic inflammation and a dysregulated immune system which contribute to impaired endothelial and microvascular function, factors that may contribute to accelerated atherosclerosis. Accurate ASCVD risk stratification and optimal risk management remains challenging in this population with many barriers that include lack of validated risk calculators, the remitting and relapsing nature of underlying disease, deleterious effect of medications used to manage rheumatic diseases, multimorbidity, decreased mobility due to joint pain, and lack of clarity about who bears the responsibility of performing CV risk assessment and management (rheumatologist vs primary care provider vs cardiologist). Despite recent advances in this field, there remains significant gaps in knowledge regarding the best diagnostic and management approach. The evolving field of Cardio-Rheumatology focuses on optimization of cardiovascular care and research in this patient population through collaboration and coordination of care between rheumatologists, cardiologists, radiologists, and primary care providers. This review aims to provide an overview of current state of knowledge about ASCVD risk stratification in patients with IRD, contributing factors including effect of medications, and review of the current recommendations for cardiovascular risk management in patients with inflammatory disease with a focus on hypertension as a key risk factor.

Cardiac Magnetic Resonance Imaging T1 and T2 Mapping in Systemic Lupus Erythematosus in Relation to Antimalarial Treatment.

PURPOSE: Patients with systemic lupus erythematosus (SLE) are at risk of cardiac disease including antimalarial-induced cardiomyopathy (AMIC). The purpose of this study is to evaluate cardiac magnetic resonance imaging parametric mapping findings in SLE patients with AMIC and investigate the relationship of T1/T2 mapping to antimalarial (AM) treatment duration. MATERIALS AND METHODS: All patients with SLE who had undergone cardiac magnetic resonance imaging with T1/T2 mapping for evaluation of suspected cardiac disease between 2018 and 2021 were evaluated and compared with healthy controls. To facilitate comparison between scanners, T1/T2 values were converted to a z -score using scanner-specific local reference values. Patients were classified into 3 groups: AMIC, myocarditis, and other (no AMIC or myocarditis). RESULTS: Forty-five SLE patients (47±17 y, 80% female; 8 [18%] with AMIC and 7 [16%] with myocarditis) and 30 healthy controls (39±15 y, 60% female) were included. Patients with AMIC had higher T1 and T2 compared with controls ( z -score 1.1±1.3 vs. 0±0.6, P =0.01 and 1.7±1.1 vs. 0±1.0, P <0.01, respectively) and lower values compared with those with myocarditis (3.7±1.6, P <0.01 and 4.0±2.0, P <0.01, respectively). T1 correlated negatively with AM treatment duration in patients without AMIC or myocarditis ( r =-0.36, P =0.048) and positively in patients with AMIC ( r =0.92, P =0.001). AM treatment duration did not correlate significantly with T1 in patients with myocarditis or with T2 in any group. CONCLUSIONS: The relationship between T1 and AM treatment duration differed between groups. Native T1 decreases with longer treatment in patients without AMIC or myocarditis, possibility due to glycosphingolipid accumulation. In patients with AMIC, increasing T1 with longer treatment could reflect fibrosis.

Cardiovascular Considerations in the Management of People With Suspected Long COVID.

Approximately 15% of adult Canadians with SARS-CoV-2 infection develop lingering symptoms beyond 12 weeks after acute infection, known as post-COVID condition or long COVID. Some of the commonly reported long COVID cardiovascular symptoms include fatigue, shortness of breath, chest pain, and palpitations. Suspected long-term cardiovascular complications of SARS-CoV-2 infection might present as a constellation of symptoms that can be challenging for clinicians to diagnose and treat. When assessing patients with these symptoms, clinicians need to keep in mind myalgic encephalomyelitis/chronic fatigue syndrome, postexertional malaise and postexertional symptom exacerbation, dysautonomia with cardiac manifestations such as inappropriate sinus tachycardia, and postural orthostatic tachycardia syndrome, and occasionally mast cell activation syndrome. In this review we summarize the globally evolving evidence around management of cardiac sequelae of long COVID. In addition, we include a Canadian perspective, consisting of a panel of expert opinions from people with lived experience and experienced clinicians across Canada who have been involved in management of long COVID. The objective of this review is to offer some practical guidance to cardiologists and generalist clinicians regarding diagnostic and treatment approaches for adult patients with suspected long COVID who continue to experience unexplained cardiac symptoms.

Cardiac Link: a retrospective cohort study evaluating a clinical pathway for expedited cardiology referral.

BACKGROUND: Outpatients presenting with chest pain often face long wait times for cardiology consultation and subsequent investigation for obstructive coronary artery disease (CAD), during which adverse cardiovascular events may occur. Our objective was to describe the design of Cardiac Link, a coronary computed tomography angiogram (CCTA)-guided rapid-access program, and evaluate its effect on cardiology consultation wait times in patients who present to primary care physicians with stable chest pain. METHODS: We conducted a retrospective cohort study at Women's College Hospital, Toronto, Ontario, Canada, between 2017 and 2020 involving eligible patients from the Family Practice Health Centre who underwent CCTA after presenting with stable chest pain or equivalent symptoms. Referring primary care physicians decided on a patient-by-patient basis to opt into the Cardiac Link program when requesting CCTA. Our primary outcome was measure of time from CCTA to cardiology consultation, and our secondary outcomes were measures of time to diagnosis from primary care consultation and CCTA booking time. RESULTS: Our analysis included 148 patients (Cardiac Link n = 98, non-Cardiac Link n = 50). Mean age of the patients was 58.4 (SD 11.2) years and 72% (107/148) were women. We found that the Cardiac Link group had a shorter time from CCTA to cardiology consultation (median 7 [interquartile range {IQR} 6-20] d v. median 100 [IQR 40-138] d; p = 0.01), shorter time to diagnosis (median 33 [IQR 22-55] d v. median 86 [IQR 40-112] d; p < 0.001) and shorter CCTA booking time (median 18 [IQR 11-31] d v. median 65 [IQR 24-92] d; p < 0.001) compared with the non-Cardiac Link group. INTERPRETATION: We determined that the Cardiac Link program reduced cardiology consultation wait times for symptomatic patients who were suspected of having CAD. Our study shows the viability of CCTA-guided rapid-access programs to expedite specialist consultation and reduce unnecessary referral for patients presenting to primary care physicians with stable chest pain.

Statin Use for Primary Cardiovascular Disease Prevention Is Low in Inflammatory Arthritis.

BACKGROUND: Patients with inflammatory arthritis (IA) are at high risk for atherosclerotic cardiovascular disease (ASCVD), yet management of dyslipidemia is infrequently prioritized. We applied Canadian dyslipidemia guidelines to determine how many patients with IA would be eligible for primary prevention with statins. METHODS: We conducted a cross-sectional study of patients with IA in a cardio-rheumatology clinic, with no known CVD and without statin therapy at cohort entry. We stratified patients by Framingham Risk Score (FRS) and summarized the proportion meeting guideline statin-indicated criteria. Multivariable logistic regression analyses determined the association of variables with statin indication after adjustment for age, sex, traditional ASCVD risk factors, and arthritis characteristics. RESULTS: Among 302 patients, most had rheumatoid arthritis (59%). Mean age was 58 years, and 71% were female. Overall, 50% of the cohort was eligible for statin therapy. The majority was low FRS risk category (68%), and the most frequent qualifier for statins was elevated apolipoprotein B (ApoB) levels or low-density lipoprotein cholesterol (LDL-c) levels. In the intermediate FRS group, 91% met criteria for statin therapy based on the presence of a coronary artery calcification (CAC) score > 0 or an elevated high-sensitivity C-reactive protein. Male sex, hypertension, elevated ApoB, and a CAC score > 0 were the factors most strongly associated with indication for statin therapy. CONCLUSIONS: Statin therapy is suboptimal in IA despite a significant number of patients meeting indication based on lipoprotein thresholds or CAC scores. Understanding the barriers and potential facilitators of implementing and interpreting these CVD screening tools in IA is needed.

The Canadian Women's Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 4: Sex- and Gender-Unique Disparities: CVD Across the Lifespan of a Woman.

Women have unique sex- and gender-related risk factors for cardiovascular disease (CVD) that can present or evolve over their lifespan. Pregnancy-associated conditions, polycystic ovarian syndrome, and menopause can increase a woman's risk of CVD. Women are at greater risk for autoimmune rheumatic disorders, which play a role in the predisposition and pathogenesis of CVD. The influence of traditional CVD risk factors (eg, smoking, hypertension, diabetes, obesity, physical inactivity, depression, anxiety, and family history) is greater in women than men. Finally, there are sex differences in the response to treatments for CVD risk and comorbid disease processes. In this Atlas chapter we review sex- and gender-unique CVD risk factors that can occur across a woman's lifespan, with the aim to reduce knowledge gaps and guide the development of optimal strategies for awareness and treatment.

Les femmes présentent des facteurs de risque de maladies cardiovasculaires (MCV) uniques, liés au sexe et au genre, qui peuvent se manifester ou évoluer tout au long de leur vie. Les troubles médicaux associés à la grossesse, le syndrome des ovaires polykystiques et la ménopause peuvent augmenter le risque de MCV chez une femme. Les femmes sont plus exposées aux troubles rhumatologiques auto-immuns, qui jouent un rôle dans la prédisposition et dans la pathogenèse des MCV. L'influence des facteurs de risque traditionnels pour les MCV (par exemple, le tabagisme, l'hypertension, le diabète, l'obésité, la sédentarité, la dépression, l'anxiété et les antécédents familiaux) est plus importante chez les femmes que chez les hommes. Enfin, il existe des différences entre les sexes dans la réponse aux traitements du risque de MCV et des processus pathologiques comorbides. Dans ce chapitre de l'Atlas, nous passons en revue les facteurs de risque de MCV propres au sexe et au genre qui peuvent survenir tout au long de la vie d'une femme, dans le but de réduire les lacunes dans les connaissances et d'orienter l'élaboration de stratégies optimales de sensibilisation et de traitement.

Effect of a neck compression collar on cardiorespiratory and cerebrovascular function in postural orthostatic tachycardia syndrome (POTS).

Postural orthostatic tachycardia syndrome (POTS) is accompanied by reduced brain blood flow, autonomic dysfunction, and orthostatic intolerance. We hypothesized that wearing a neck compression collar would attenuate orthostatic symptoms, increase brain blood flow, and influence autonomic reflexes. Ten participants with POTS (9 women, age: 36 ± 10) underwent two trials of supine rest, paced deep breathing (6 breaths/min), Valsalva maneuver (40 mmHg for 15 s), and 70° upright tilt. For one trial, participants wore a neck compression device (Q30 Innovations). Blood pressure, heart rate (HR), brain blood flow velocity, stroke volume, respiratory rate, and end-tidal gases were continuously measured. The Vanderbilt Orthostatic Symptom Score was compiled at the end of tilt. The use of the collar reduced the orthostatic symptom score of participants with POTS during upright tilt (26.9 ± 12.5 to 18.7 ± 13.1, P = 0.04). Collar compression in the supine condition reduced the low-frequency domain of HR variability (60 ± 18 to 51 ± 23 normalized units, P = 0.04) and increased the change in HR (15 ± 5 to 17 ± 6 bpm, P = 0.02) and E:I ratio (1.2 ± 0.1 to 1.3 ± 0.1, P = 0.01) during paced deep breathing. Throughout tilt, wearing the collar reduced respiratory rate (baseline: 13 ± 3 to 12 ± 4 breath/min; tilt: 18 ± 5 to 15 ± 5 breath/min; main effect of collar P = 0.048), end-tidal oxygen (baseline: 115 ± 5 to 112 ± 5 mmHg; tilt: 122 ± 10 to 118 ± 11 mmHg; main effect of collar P = 0.026). In participants with POTS, wearing the Q-collar reduced orthostatic symptoms, increased the HR response to deep breathing, and decreased resting ventilation.NEW & NOTEWORTHY We found that using a neck compression collar alleviated orthostatic symptoms in upright posture in participants with postural orthostatic tachycardia syndrome (POTS). This could be due to compression of the baroreceptors and subsequent changes in autonomic function. Indeed, we observed increased heart rate responsiveness to paced deep breathing and reductions of respiratory rate and end-tidal O2 (suggesting reduced ventilation). Further, wearing the collar reduced mean blood velocity in the brain during Valsalva perhaps due to higher brain blood volume.

Relationships between vascular resistance and energy deficiency, nutritional status and oxidative stress in oestrogen deficient physically active women.

OBJECTIVE: Oestrogen deficiency contributes to altered cardiovascular function in premenopausal amenorrheic physically active women. We investigated whether other energy deficiency-associated factors might also be associated with altered cardiovascular function in these women. DESIGN: A prospective observational study was completed at a research facility at the University of Toronto. PARTICIPANTS: Thirty-two healthy premenopausal women (18-35 years old) were studied; 9 sedentary and ovulatory; 14 physically active and ovulatory; and 8 physically active and amenorrheic. MEASUREMENTS: We measured calf vascular resistance, resting heart rate, dietary energy intake, resting energy expenditure and serum measures of homocysteine, high-sensitivity C-reactive protein, oxidized low-density lipoproteins, total T(3), ghrelin, leptin and insulin. RESULTS: Groups were similar (P > 0.05) in age (25.1 +/- 0.8 years; mean +/- SEM), weight (57.3 +/- 1.1 kg), and BMI (21.4 +/- 0.3 kg/m(2)). Resting vascular resistance and ghrelin were highest (P < 0.05, main effect), and total T(3) and energy expenditure adjusted for fat free mass lowest (P < 0.05, main effect) in oestrogen deficient women. Using pooled data for stepwise multiple regression modelling: ghrelin and resting energy expenditure adjusted for fat free mass were associated with resting vascular resistance (R(2) = 0.398, P = 0.018); adjusted dietary energy intake was associated with peak-ischaemic vascular resistance (R(2) = 0.231, P = 0.015). Adjusted resting energy expenditure (r = 0.624, P < 0.001) and total T(3) correlated (r = 0.427, P = 0.019) with resting heart rate. Homocysteine, high-sensitivity C-reactive protein and oxidized low-density lipoproteins were similar (P > 0.05, main effect) among the groups, and were unrelated to cardiovascular measures. CONCLUSION: Altered resting vascular resistance in premenopausal oestrogen deficient physically active amenorrheic women is not associated with vascular inflammation or oxidative stress, but rather with parameters that reflect metabolic allostasis and dietary intake, suggesting a potential role for chronic energy deficiency in vascular regulation.

Prevalence and associated factors of resting electrocardiogram abnormalities among systemic lupus erythematosus patients without cardiovascular disease.

BACKGROUND: Electrocardiogram (ECG) cardiovascular disease (CVD) abnormalities (ECG-CVD) are predictive of subsequent CVD events in the general population. Systemic lupus erythematosus (SLE) patients are vulnerable to CVD. We aimed to determine the prevalence of ECG-CVD in SLE patients and to examine the risk factors associated with ECG-CVD. METHODS: A 12-lead resting supine ECG was performed on consecutive adult patients attending the clinic. One cardiologist interpreted the ECGs. ECG-CVD were defined as the presence of one or more of the following 4 elements (ECG-4): ST-segment and/or T-wave abnormalities, left ventricular hypertrophy (LVH), left axis deviation (LAD), left bundle branch block (LBBB) and right bundle branch block (RBBB). ECG-5 included the same elements as ECG-4 and the Q-wave. Repeated measurement data were created and the associations between ECG-4/ECG-5 and demographics were evaluated with univariate and multivariate Cox regression models. RESULTS: Of 487 SLE patients, 104 (21.4%) and 118 (24.2%) patients had one or more of the ECG-4 and ECG-5 elements, respectively. A higher prevalence of ECG-CVD was found in patients with a longer SLE disease duration, and the burden of ECG-CVD elements increased with age. Increased age, active SLE disease, and damage were associated with ECG4 and ECG-5, while treatment of hyperlipidemia was protective. CONCLUSION: A high prevalence of ECG-4 (21.4%) and ECG-5 (24.2%) was found in this SLE cohort. Controlling SLE disease activity is important since it was associated with ECG-4 and ECG-5. Early identification of ECG-4 and ECG-5 in SLE patients might allow for better stratification and risk management.

After-exercise heart rate variability is attenuated in postmenopausal women and unaffected by estrogen therapy.

OBJECTIVE: Delayed heart rate (HR) recovery in the immediate postexercise period has been linked to adverse cardiovascular prognosis. The after effects of an acute bout of exercise on HR modulation in postmenopausal women (PMW) and the influence of estrogen therapy are unknown. METHODS: In 13 sedentary PMW (54 ± 2 y, mean ± SEM), we assessed HR variability (HRV)--an index of HR modulation--and the influence of estrogen therapy on HRV. HRV in the frequency domain was quantified during supine rest and again 60 minutes after treadmill exercise for 45 minutes, at 60% VO2peak. PMW were studied before and after 4 weeks of oral estradiol. To obtain reference values for the after effects of exercise on HRV in healthy young women, 14 premenopausal women (PreM) completed the identical exercise protocol. RESULTS: Compared with PreM, PMW demonstrated lower high frequency (vagal modulation) and total HRV (P < 0.05) at rest. In PreM, all HRV values were similar before and after exercise. In contrast, in PMW after exercise, despite having identical HR to PreM, high frequency and total HRV were all lower (all P ≤ 0.01) compared with pre-exercise HRV values. Estrogen therapy had no effect on pre or postexercise values for HRV. CONCLUSIONS: When compared with PreM, PMW have identical HR, but lower vagal HR modulation at rest and delayed HRV recovery after exercise. Estrogen does not restore baseline HRV or accelerate HRV recovery postexercise, suggesting aging rather than estrogen deficiency per se may lower HRV in PMW.

The risk of myocardial infarction with aromatase inhibitors relative to tamoxifen in post-menopausal women with early stage breast cancer.

BACKGROUND: Aromatase inhibitors (AIs) may increase cardiovascular risk relative to tamoxifen in post-menopausal women with breast cancer. This risk has not been well-quantified outside of clinical trials. METHODS: Observational population-based cohort study of women aged >55 years diagnosed with stage I-III breast cancer between 2005 and 2010. Women treated with AIs or tamoxifen were followed to March 2012. The primary outcome was hospitalisation for myocardial infarction (MI). Cause-specific hazards were compared using tamoxifen as the reference group. Inverse probability of treatment weighting using the propensity score was used to reduce confounding due to measured baseline covariates. Results were confirmed using two cause-specific hazards models. Subgroup analyses included women aged ≥66 years, those with prior ischaemic heart disease, and a 'lower-risk group' aged <74 years with stage I-II cancer and no prior ischaemic heart disease. RESULTS: In 7409 aromatase inhibitor-treated and 1941 tamoxifen-treated women, the median age was 71 versus 74 years, respectively (p < 0.001). Baseline prevalence of ischaemic heart disease was similar (17.0% versus 16.9%, p = 0.96). Over a mean of 1184 d of follow-up, there were 123 hospitalisations for MI; the cause-specific hazard was higher with AIs (hazard ratio 2.02; 95% confidence interval 1.16-3.53 in the weighted sample). We observed comparable patterns within pre-defined subgroups and when adjusted using cause-specific hazards models. CONCLUSION: Aromatase inhibitors are associated with a higher risk of MI compared with tamoxifen. This risk should be accounted for when managing aromatase inhibitor-treated women.

Sex differences in depression after coronary artery bypass graft surgery.

BACKGROUND: Previous research suggests that after coronary artery bypass graft (CABG) surgery, women fare worse than men. This study investigates sex differences in depression during recovery from CABG surgery. METHODS: We followed 137 patients (72 men, 65 women) undergoing elective isolated first CABG surgery between July 2003 and April 2004. Patients were interviewed < or = 28 days before surgery and between 6 and 12 weeks after surgery. Patients completed a structured diagnostic interview for major depressive disorder (MDD) and the Beck Depression Inventory (BDI). Clinical data were retrieved from patient charts. RESULTS: Prevalence of MDD before surgery was 28.2%, but decreased to 16.4% after surgery (P = .038). Women had significantly more depressive symptoms than men pre-CABG, with a mean BDI of 12.5 (95% CI 10.6-14.4) for women versus 8.0 (95% CI 6.3-9.8) for men (P = .0001), but not post-CABG. There was a significant sex-by-time interaction with depressive symptoms in women improving almost 6-fold more than in men, with BDI change scores of 4.1 (95% CI 2.0-6.1) for women versus 0.7 (95% CI-1.0-2.5) for men (P = .008). The interaction remained significant after adjusting the model for the predetermined baseline characteristics education, social support, and operative risk. CONCLUSIONS: Women had more depressive symptoms than men pre-CABG, but improved to a level comparable to men post-CABG. Women benefited from CABG as much or more than men in terms of their mental health. Preoperative depressive symptoms should not preclude women from CABG surgery.

Exercise as an alternative to oral estrogen for amelioration of endothelial dysfunction in postmenopausal women.

BACKGROUND: Both exercise and postmenopausal estrogen therapy augment endothelial function. We hypothesized that their interaction would be additive. The study objectives were to determine in postmenopausal women (1) the effects of an acute bout of exercise on brachial artery endothelium-dependent flow-mediated vasodilation (FMD), (2) whether these responses to exercise are augmented by concurrent estrogen treatment, and (3) whether these 2 interventions, independently or together, achieve FMD values observed in premenopausal women. METHODS: In postmenopausal women (n = 13; age 54 +/- 2 [mean +/- SE] years), FMD was quantified during supine rest and again 60 minutes after treadmill exercise for 45 minutes at 60% V* O2max. Subjects were studied twice: before and after 4 weeks of oral estradiol. To obtain reference normal values, FMD was determined concurrently in 14 premenopausal (28 +/- 1 years) women under identical basal conditions. RESULTS: Flow-mediated vasodilation in postmenopausal women, markedly impaired when compared with premenopausal women (5.3% +/- 0.5% vs 12.1% +/- 1.5%, P < .01), was significantly increased by exercise (to 9.9% +/- 0.6%, P < .01). In contrast, after estrogen, FMD was augmented at rest (P < .01) but was not further enhanced after exercise (11.5% +/- 0.6% vs 9.9% +/- 0.5%, P = .3). Both interventions increased, independently, FMD to values in premenopausal women (P > .05). CONCLUSIONS: In postmenopausal women, both acute exercise and estrogen therapy normalize FMD. However, their effects are not additive, possibly because of redundancy of nitric oxide signaling pathways activated by these 2 interventions. When considered in the context of recent trials with adverse cardiovascular outcomes, these results reinforce the therapeutic potential of exercise as an alternative nonpharmacological intervention to estrogen in postmenopausal women with endothelial dysfunction.