Daria Frestad

Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease: The iPOWER Study

Background The majority of women with angina‐like chest pain have no obstructive coronary artery disease when evaluated with coronary angiography. Coronary microvascular dysfunction is a possible explanation and associated with a poor prognosis. This study evaluated the prevalence of coronary microvascular dysfunction and the association with symptoms, cardiovascular risk factors, psychosocial factors, and results from diagnostic stress testing. Methods and Results After screening 3568 women, 963 women with angina‐like chest pain and a diagnostic coronary angiogram without significant coronary artery stenosis (<50%) were consecutively included. Mean age (SD) was 62.1 (9.7). Assessment included demographic and clinical data, blood samples, questionnaires, and transthoracic echocardiography during rest and high‐dose dipyridamole (0.84 mg/kg) with measurement of coronary flow velocity reserve (CFVR) by Doppler examination of the left anterior descending coronary artery. CFVR was successfully measured in 919 (95%) women. Median (IQR) CFVR was 2.33 (1.98–2.76), and 241 (26%) had markedly impaired CFVR (<2). In multivariable regression analysis, predictors of impaired CFVR were age (P<0.01), hypertension (P=0.02), current smoking (P<0.01), elevated heart rate (P<0.01), and low high‐density lipoprotein cholesterol (P=0.02), but these variables explained only a little of the CFVR variation (r 2=0.09). CFVR was not associated with chest pain characteristics or results from diagnostic stress testing. Conclusion Impaired CFVR was detected in a substantial proportion, which suggests that coronary microvascular dysfunction plays a role in the development of angina pectoris. CFVR was associated with few cardiovascular risk factors, suggesting that CFVR is an independent parameter in the risk evaluation of these women. Symptom characteristics and results from stress testing did not identify individuals with impaired CFVR.

Vital Exhaustion and Coronary Heart Disease Risk: A Systematic Review and Meta-Analysis.

Objective The construct of vital exhaustion has been identified as a potential independent psychological risk factor for incident and recurrent coronary heart disease (CHD). Despite several decades of research, no systematic review or meta-analysis has previously attempted to collate the empirical evidence in this field. The purpose of this study was to review and quantify the impact of vital exhaustion on the development and progression of CHD. Methods Prospective and case-control studies reporting vital exhaustion at baseline and CHD outcomes at follow-up were derived from PubMed, PsycINFO (1980 to July 2015; articles in English and published articles only), and bibliographies. Information on aim, study design, sample size, inclusion and exclusion criteria, assessment methods of psychological risk factors, and results of crude and adjusted regression analyses were abstracted independently by two authors. Results Thirteen prospective (n = 52,636) and three case-control (cases, n = 244; controls, n = 457) studies assessed vital exhaustion and could be summarized in meta-analyses. The pooled adjusted risk of CHD in healthy populations was 1.50 (95% confidence interval [CI] = 1.22–1.85) for prospective studies, and 2.61 (95% CI = 1.66–4.10) for case-control studies using hospital controls. Risk of recurrent events in patients with CHD was 2.03 (95% CI = 1.54–2.68). The pooled adjusted risk of chronic heart failure in healthy populations was 1.37 (95% CI = 1.21–1.56), but this was based on results from only two studies. Conclusions Vital exhaustion is associated with increased risk of incident and recurrent CHD.

Risk Factors for Myocardial Infarction in Women and Men: A Review of the Current Literature

BACKGROUND Cardiovascular disease has been the leading cause of death in both sexes in developed countries for decades. In general, men and women share the same cardiovascular risk factors. However, in recent trials including both men and women sexspecific analyses have raised awareness of sex differences in cardiovascular risk factors due to both biological and cultural differences. RESULTS Women experience their first myocardial infarction (MI) 6-10 years later than men and a protective effect of their natural estrogen status prior to menopause has been suggested. Female sex hormones have been associated with a less atherogenic lipid profile and a more healthy fat distribution. These differences are attenuated following menopause. Regarding life style the prevalence of smoking is highest in men but female smokers have a relatively higher cardiovascular risk than male smokers. Men are more physically active than women while women have healthier dietary habits. Genetic factors also affect cardiovascular risk but no sex differences have been seen. Increased cardiovascular risk attributed to psychosocial distress is similar in men and women, but since women are more prone to psychosocial distress their burden of disease is greater. Compared with a healthy population the relative risk of MI in a diabetic population is higher in women than in men. No sex difference exists in the prevalence of hypertension but it has an earlier onset in men. CONCLUSION Sex differences in cardiovascular risk are becoming more apparent and paying attention to this is pivotal when addressing risk factors in preventive efforts.

The prognostic value of coronary endothelial and microvascular dysfunction in subjects with normal or non-obstructive coronary artery disease: A systematic review and meta-analysis

AIMS Coronary vascular dysfunction is linked with poor cardiovascular prognosis in patients without obstructive coronary artery disease (CAD) but a critical appraisal of the literature is lacking. METHODS AND RESULTS We performed a systematic review and meta-analysis to quantify the cardiovascular risk associated with endothelial dependent and non-endothelial dependent coronary vascular dysfunction in patients with normal or non-obstructive CAD (epicardial stenosis <50%). Prospective cohort studies that reported coronary vascular dysfunction at baseline and cardiovascular outcomes at follow-up were included. We identified 52 papers of which 26 were included in the meta-analyses. Study populations included stable angina (n=15), heart failure (n=4), diabetes (n=2), hypertrophic obstructive cardiomyopathy (n=2), chronic kidney disease, aortic stenosis and left atrial enlargement (each n=1): RR estimates were similar in patients with stable angina and other patient groups. For epicardial endothelial dependent dysfunction (six studies, 243 events in 1192 patients) the summarized RR was 2.38 (95% confidence intervals (95% CI) 1.74-3.25), for non-endothelial dependent dysfunction assessed as coronary flow velocity reserve (CFVR) by echocardiography (10 studies, 428 events in 5134 patients) RR was 4.58 (95% CI 3.58-5.87) and for coronary flow reserve (CFR) by PET (10 studies, 538 events in 3687 patients) RR was 2.44 (95% CI 1.80-3.30). However, RR estimates were robust in a series of sensitivity analyses. CONCLUSION The presence of coronary vascular dysfunction in patients with normal or non-obstructive CAD predicts adverse cardiovascular outcome. Multicentre studies and uniform guidelines for assessing coronary vascular dysfunction are encouraged.

Giant aneurysm in a left coronary artery fistula: diagnostic cardiovascular imaging and treatment considerations

Congenital coronary artery fistula complicated with giant coronary artery aneurysm is a very rare condition. In this case report, we present a 65-year-old woman, referred to us with a continuous heart murmur, occasional atypical chest pain and few episodes of fainting. A giant aneurysm and a coronary–pulmonary fistula were diagnosed using multiple cardiovascular imaging modalities to provide a sufficient anatomical picture. The patient was considered at high risk of sudden death from aneurysm rupture and received surgical treatment. Subsequent histopathological examination revealed a true aneurysm with severe wall calcifications, ulcerations and large areas with marked thinning of the wall. The postoperative course was uneventful.

Effect of pulmonary hyperinflation on central blood volume: An MRI study

Pulmonary hyperinflation attained by glossopharyngeal insufflation (GPI) challenges the circulation by compressing the heart and pulmonary vasculature. Our aim was to determine the amount of blood translocated from the central blood volume during GPI. Cardiac output and cardiac chamber volumes were assessed by magnetic resonance imaging in twelve breath-hold divers at rest and during apnea with GPI. Pulmonary blood volume was determined from pulmonary blood flow and transit times for gadolinium during first-pass perfusion after intravenous injection. During GPI, the lung volume increased by 0.8±0.6L (11±7%) above the total lung capacity. All cardiac chambers decreased in volume and despite a heart rate increase of 24±29 bpm (39±50%), pulmonary blood flow decreased by 2783±1820mL (43±20%). The pulmonary transit time remained unchanged at 7.5±2.2s and pulmonary blood volume decreased by 354±176mL (47±15%). In total, central blood volume decreased by 532±248mL (46±14%). Voluntary pulmonary hyperinflation leads to ∼50% decrease in pulmonary and central blood volume.

Women with Stable Angina Pectoris and No Obstructive Coronary Artery Disease: Closer to a Diagnosis

A large proportion of women with chest pain have no obstructive coronary artery disease. Recent studies have demonstrated that these women continue to have symptoms and are at increased risk of cardiovascular morbidity and mortality. Coronary microvascular dysfunction (CMD) leads to an impairment of blood flow regulation to the myocardium and possible transient ischaemia. CMD is a disease entity with several pathophysiologic aspects and diagnostic modalities continue to be developed. However, due to the complexity of the disease, it remains elusive whether CMD is the explanation for the symptoms and the poor prognosis in women with angina and no obstructive coronary artery disease.

Peripheral Endothelial Function and Coronary Flow Velocity Reserve Are Not Associated in Women with Angina and No Obstructive Coronary Artery Disease: The iPOWER Study

Purpose: We investigated whether impaired flow-mediated dilation (FMD) and plasma biomarkers reflecting endothelial dysfunction are associated with coronary microvascular dysfunction (CMD) in women with angina and no obstructive coronary artery disease (CAD). Methods: Patients (n = 194) were randomly selected women with angina pectoris and no obstructive CAD (<50% stenosis). A reference population of asymptomatic women without CAD (n = 25) was included. We measured FMD in the brachial artery by high-resolution ultrasound. Coronary flow velocity reserve (CFVR) was assessed by transthoracic Doppler flow echocardiography (TTDE) of the left anterior descending artery during rest and high-dose dipyridamole infusion. CMD was defined as CFVR <2. Results: FMD and CFVR were measured in 128 patients and 21 controls. Mean (SD) age was 64.5 (8.9) years, mean CFVR was 2.3 (2.0-2.7), and mean FMD was 8.4% (4.8%) in angina patients. Angina patients had a higher risk factor burden compared with the reference population. Measures of peripheral endothelial dysfunction and endothelial plasma biomarkers did not differ according to angina or CFVR. CFVR and FMD did not correlate (Spearman ρ = -0.07, p = 0.45). Conclusions: FMD and biomarkers of endothelial dysfunction did not identify individuals with CMD assessed as impaired CFVR by TTDE in women with angina and no obstructive CAD.