Reduced coronary flow velocity reserve in women with previous pre-eclampsia: link to increased cardiovascular disease risk.

OBJECTIVES: To evaluate differences in coronary microvascular function approximately 12 years after delivery between women who had had early- (EO-PE) or late- (LO-PE) onset pre-eclampsia and those who had had a normotensive pregnancy, and to assess the relationship between microvascular function and myocardial deformation at follow-up in these women. METHODS: This was a case-control study of 88 women who had delivered at the Department of Gynecology and Obstetrics, Randers Regional Hospital, Randers, Denmark, between 1998 and 2008. Coronary flow velocity reserve (CFVR) was assessed by Doppler echocardiography approximately 12 years after delivery. Women were grouped according to whether the pregnancy had been complicated by EO-PE (n = 29) or LO-PE (n = 20), or had been normotensive (controls) (n = 39). Study groups were matched for maternal age and time since delivery. CFVR at follow-up was compared between the study groups. Regression analysis was used to assess the association between gestational age at onset of PE and CFVR. The association between left ventricular global longitudinal strain (LV-GLS) and CFVR at follow-up was also evaluated. RESULTS: Resting coronary flow velocity assessed 12 years after delivery was comparable between the study groups (P = 0.55), whereas peak hyperemic flow velocity was significantly lower in the EO-PE group than in the LO-PE group (P < 0.01) and controls (P < 0.0001). As such, mean CFVR at follow-up was significantly lower in the EO-PE group than in the LO-PE group (P < 0.01) and controls (P < 0.0001). CFVR was < 2.5 in 48% of women in the EO-PE group, 25% of those in the LO-PE group and 8% of controls (P < 0.01). There was a significant positive association between gestational age at diagnosis of PE and CFVR at 12-year follow-up (ß1 = 1.8 (95% CI, 0.8-2.9); P < 0.01). This relationship remained significant after adjustment for cardiovascular risk factors, namely mean arterial blood pressure, glycated hemoglobin level, body mass index, low-density lipoprotein cholesterol level and smoking status (P < 0.05). There was a significant association between LV-GLS and CFVR in women who had had PE (ß1 = -1.5 (95% CI, -2.2 to -0.9); R2 = 0.33, P < 0.0001). CONCLUSIONS: Low gestational age at onset of PE, both as a continuous variable and when categorized as early onset, was associated with decreased CFVR 12 years after delivery. Nearly 50% of women who had had EO-PE had CFVR < 2.5 at follow-up. Reduced CFVR in women who had had PE was associated with subclinical myocardial dysfunction in terms of reduced LV-GLS. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Association between baseline vitamin D metabolite levels and long-term cardiovascular events in patients with rheumatoid arthritis from the CIMESTRA trial: protocol for a cohort study with patient-record evaluated outcomes.

INTRODUCTION: Cardiovascular morbidity and mortality is increased in patients with rheumatoid arthritis (RA), and among these patients, the prevalence of hypovitaminosis D is high. Moreover, low vitamin D levels have been associated with increased cardiovascular risk in healthy subjects. OBJECTIVE: To evaluate the long-term risk of cardiovascular events in patients having low total 25-hydroxyvitamin D levels at baseline compared with patients with normal levels, in an efficiently treated, closed cohort of patients with an early diagnosis of RA. METHODS AND ANALYSIS: This study is a prospective, closed, blinded endpoint cohort study, based on secondary analyses from a previous randomised trial (CIMESTRA study; NCT00209859, approved September 1999) including 160 patients with an early diagnosis of RA from Danish University clinics. Primary outcome will be the proportion of patients with any cardiovascular event in the follow-up period, evaluated using systematic journal audits. Logistic regression models will test the hypothesis that there are more cardiovascular events in enrolled patients with a low level of vitamin D (< 50 nmol/L). Secondarily, Cox regression models, based on survival analysis, will determine the extent to which independent variables (including different levels of vitamin D at baseline) predict whether a cardiovascular event will occur, and also when this will be. ETHICS AND DISSEMINATION: All patients have received verbal and written information before enrolment, and have given written consent at baseline. To disseminate comprehension of factors of prognostic importance to cardiovascular outcome in RA, we will attempt to have a first draft ready no later than 1 year after the adjudication process has finished. If low vitamin D levels can predict cardiovascular events in RA, it is relevant to take into account in a prediction model, to be considered by patients, physicians and other decision-makers. TRIAL REGISTRATION NUMBER: The parental controlled trial is registered as NCT00209859.

Left ventricular function at two-year follow-up in treatment-naive rheumatoid arthritis patients is associated with anti-cyclic citrullinated peptide antibody status: a cohort study.

OBJECTIVES: In rheumatoid arthritis (RA), the role of autoimmunity, especially anti-cyclic citrullinated peptide antibody (anti-CCP) level, and the time-course of left ventricular (LV) function is unknown. The objective was to assess LV function and the amount of coronary calcium in relation to anti-CCP levels in a cohort of treatment-naive RA patients, and to assess changes in these parameters during a 2 year follow-up period. METHOD: Sixty-six steroid- and disease-modifying anti-rheumatic drug-naive RA patients were treated with methotrexate according to the Danish national guidelines. We assessed LV function by conventional echocardiography and speckle-tracking echocardiography. We estimated the amount and progression of coronary calcium by coronary computed tomography. Patients were examined at the time of diagnosis and after 2 years. RESULTS: Patients with elevated anti-CCP at baseline and after 2 years, compared to those with non-persistently elevated anti-CCP, had significantly less improvement in S´ (1 ± 1.4 cm/s vs 0.2 ± 0.9 cm/s; p = 0.04) and a worsening in global longitudinal systolic strain (GLS) (0.6 ± 1.8% vs -1 ± 2.8%; p = 0.04). There was a significant correlation between ΔGLS over 2 years and anti-CCP at 2 year follow-up (r = 0.36; p = 0.006). We observed a small progression of coronary calcium score during the 2 year follow-up period. No differences in progression were found between patients with high anti-CCP titres at baseline and 2 year follow-up (n = 12) and patients with normal/low anti-CCP titres (n = 32) (23.8 ± 40.3 vs 22.6 ± 68.9; p = 0.96). CONCLUSIONS: Deformation analysis by speckle-tracking echocardiography is a valuable tool to detect early development of myocardial dysfunction despite normal ejection fraction in RA.

Myocardial oedema in acute myocarditis detected by echocardiographic 2D myocardial deformation analysis.

AIMS: The clinical diagnosis of acute myocarditis is based on symptoms, electrocardiography, elevated myocardial necrosis biomarkers, and echocardiography. Often, conventional echocardiography reveals no obvious changes in global cardiac function and therefore has limited diagnostic value. Myocardial deformation imaging by echocardiography is an evolving method used to characterize quantitatively longitudinal systolic function, which may be affected in acute myocarditis. The aim of our study was to assess the utility of echocardiographic deformation imaging of the left ventricle in patients with diagnosed acute myocarditis in whom cardiovascular magnetic resonance (CMR) evaluation was performed. METHODS AND RESULTS: We included 28 consecutive patients (mean age 32 ± 13 years) with CMR-verified diagnosis of acute myocarditis according to the Lake Louise criteria. Cardiac function was evaluated by a comprehensive assessment of left ventricular (LV) function, including 2D speckle-tracking echocardiography. We found no significant correlation between the peak values of cardiac enzymes and the amount of myocardial oedema assessed by CMR (troponin: r= 0.3; P = 0.05 and CK-MB: r = 0.1; P = 0.3). We found a larger amount of myocardial oedema in the basal part of the left ventricle [American Heart Association (AHA) segments 1-6] in inferolateral and inferior segments, compared with the anterior, anterolateral, anteroseptal, and inferoseptal segments. In the mid LV segments (AHA segments 7-12), this was more pronounced in the anterior, anterolateral, and inferolateral segments. Among conventional echocardiographic parameters, LV function was not found to correlate with the amount of myocardial oedema of the left ventricle. In contrast, we found the wall motion score index to be significantly correlated with the amount of myocardial oedema, but this correlation was only present in patients with an extensive amount of oedema (>11% of the total left ventricle). Global longitudinal systolic myocardial strain correlated significantly with the amount of oedema (r = 0.65; P < 0.001). We found that both the epicardial longitudinal and the endocardial longitudinal systolic strains were significantly correlated with oedema (r = 0.55; P = 0.003 and r = 0.54; P < 0.001). CONCLUSION: In patients with acute myocarditis, 2D speckle-tracking echocardiography was a useful tool in the diagnostic process of acute myocarditis. Global longitudinal strain adds important information that can support clinical and conventional echocardiographic evaluation, especially in patients with preserved LV ejection fraction in relation to the diagnosis and degree of myocardial dysfunction.