Normative reference data, determinants, and clinical implications of right atrial reservoir function in women assessed by 2D speckle-tracking echocardiography.

AIM: We aim to determine normative reference data of phasic right atrial (RA) strain and to investigate determinants, possible clinical implications as well as feasibility and reproducibility of RA strain analysis. METHODS AND RESULTS: Right atrial strain was analyzed in 266 participants of the cross-sectional Berlin Female Risk Evaluation (BEFRI) study using 2D speckle-tracking echocardiography (2D STE). To determine reference values, phasic RA strain was determined in a subgroup of 123 individuals without known cardiovascular diseases or risk factors. Mean RA reservoir strain (RAS), RA conduit, and contraction strain in this reference group were 44.9 ± 11.6%, 27.1 ± 9.5%, and 17.0 ± 5.9%, respectively. Regarding possible clinical implications, RAS was significantly reduced in women with a BMI ≥ 25, compared with women with a BMI < 25 (35.5 ± 11.1% vs 43.4 ± 11.6%, P < 0.0001). RA strain analysis showed a good feasibility (92.7%); intra- and inter-observer variability was low (<5%). BMI, global longitudinal peak systolic LV strain (LVGLS%), RA area, TAPSE, and early diastolic myocardial relaxation velocity of the RV (RV-e') were significantly associated with RA mechanics in a multivariate logistic regression analysis. CONCLUSION: In this cross-sectional trial, we determined reference values, feasibility and reproducibility, clinical and echocardiographic determinants, and possible clinical implications of RA strain analysis. Our data may help to introduce the analysis of RA mechanics into future echocardiographic routine use.

Right heart function in impaired left ventricular diastolic function: 2D speckle tracking echocardiography-based and Doppler tissue imaging-based analysis of right atrial and ventricular function.

AIM: The aim of our study was to describe right atrial (RA) and right ventricular (RV) function, assessed by Doppler tissue imaging and 2D speckle tracking echocardiography (2DSTE), in women with signs of early impaired left ventricular diastolic function (DD). METHODS AND RESULTS: In a cross-sectional trial, standard parameters of diastolic and right heart function were investigated in 438 women of the Berlin Female Risk Evaluation (BEFRI) study. In a subset of women, average peak systolic RA strain (RAS), as well as the average peak systolic RV strain of the free wall (RVS free wall) and of all RV segments (average RV strain; RVS Avg), was analyzed using 2DSTE. Compared to women with normal diastolic function (DD0), RAS, RVS free wall and RVS Avg were significantly reduced in DD (43.1% ± 11.9%, -26.7% ± 5.6%, and -23.3% ± 3.5% in DD0; vs 35.1% ± 10.4%, -23.9% ± 5.5%, and -20.6% ± 3.8% in DD; P < .01). Peak RV myocardial velocity (RV-IVV) and acceleration during isovolumetric contraction (RV-IVA) were markedly higher in DD (15.0 ± 3.9 cm/s and 3.1 ± 1.0 m/s² in DD vs 11.9 ± 3.2 cm/s and 2.8 ± 0.8 m/s² in DD0; P < .05). RAS and RV-IVV were significantly associated with DD after adjustment to age, BMI, and left atrial strain in multivariate regression analysis. CONCLUSION: Systolic right heart function is significantly altered in DD. DTI as well as 2DSTE constitute sensitive echocardiographic tools that enable the diagnosis of impaired right heart mechanics in early-staged DD.

Left Atrial Function in Preclinical Diastolic Dysfunction: Two-Dimensional Speckle-Tracking Echocardiography-Derived Results from the BEFRI Trial.

BACKGROUND: Patients with preclinical left ventricular (LV) diastolic dysfunction (DD) are prone to develop heart failure with preserved ejection fraction. Although left atrial (LA) enlargement and deterioration of LA function in apparent DD and heart failure with preserved ejection fraction have been previously described, data regarding phasic LA strain (LAS) in preclinical DD are scarce. METHODS: In a cross-sectional trial, echocardiographic parameters of DD, LA volume index, and global LA reservoir, conduit, and pump function were prospectively analyzed in 473 women from the general population in Berlin, Germany (BErlin Female RIsk evaluation (BEFRI) study), using standard and two-dimensional speckle-tracking echocardiography. RESULTS: One hundred thirty-one women (29.7%) showed early-stage DD (impaired relaxation [DD1]) and 22 (5.0%) showed an echocardiographically more advanced stage of DD (pseudonormal filling [DD2]). Compared with women with normal diastolic function (DD0), those with DD1 displayed lower LA reservoir and conduit function (DD0, 43.2 ± 8.5% and 27.2 ± 8.0%; DD1, 33.3 ± 8.0% and 16.1 ± 7.1%; P < .001) but significantly higher LA pump function (DD0, 17.6 ± 5.4%; DD1, 18.9 ± 5.5%; P < .05). In patients with DD2, all three phases of LAS were markedly impaired compared with those with DD0 (reservoir, conduit, and pump function, 29.0 ± 6.3%, 15.1 ± 5.4% [P < .001], and 14.9 ± 4.1% [P < .05], respectively). LA reservoir and conduit function was significantly associated with DD; in receiver operating characteristic curve analysis, these parameters showed higher diagnostic accuracy in detecting early DD compared with LA volume index. In multivariate analysis, LA reservoir strain remained significantly associated with DD. CONCLUSIONS: All three components of LAS showed specific alterations in different stages of DD. LA reservoir and conduit function was markedly reduced before symptoms, LA enlargement, and elevations of noninvasively estimated LV filling pressures occurred. Analysis of LA function featured higher discriminative strength in diagnosing early-stage DD compared with the well-established parameter LA volume index. Assessment of LAS allows diagnosis of impaired LA function and DD in a subclinical stage and might enable timely preventive and therapeutic interventions.

Cardiovascular risk factor distribution and subjective risk estimation in urban women--the BEFRI study: a randomized cross-sectional study.

BACKGROUND: Awareness represents a major modulator for the uptake of preventive measures and healthy life-style choices. Women underestimate the role of cardiovascular diseases as causes of mortality, yet little information is available about their subjective risk awareness. METHODS: The Berlin Female Risk Evaluation (BEFRI) study included a randomized urban female sample aged 25-74 years, in which 1,066 women completed standardized questionnaires and attended an extensive clinical examination. Subjective estimation was measured by a 3-point Likert scale question asking about subjective perception of absolute cardiovascular risk with a 10 year outlook to be matched to the cardiovascular risk estimate according to the Framingham score for women. RESULTS: An expected linear increase with age was observed for hypertension, hyperlipidemia, obesity, and vascular compliance measured by pulse pressure. Knowledge about optimal values of selected cardiovascular risk factor indicators increased with age, but not the perception of the importance of age itself. Only 41.35% of all the participants correctly classified their own cardiovascular risk, while 48.65% underestimated it, and age resulted as the most significant predictor for this subjective underestimation (OR = 3.5 for age >50 years compared to <50, 95% CI = 2.6-4.8, P <0.0001). Therefore, although socioeconomic factors such as joblessness (OR = 1.9, 95% CI = 1.4-2.6, P <0.0001) and combinations of other social risk factors (low income, limited education, simple job, living alone, having children, statutory health coverage only; OR = 1.5, 95% CI = 1.1-2.1, P = 0.009) also significantly influenced self-awareness, age appeared as the strongest predictor of risk underestimation and at the same time the least perceived cardiovascular risk factor. CONCLUSIONS: Less than half of the women in our study population correctly estimated their cardiovascular risk. The study identifies age as the strongest predictor of risk underestimation in urban women and at the same time as the least subjectively perceived cardiovascular risk factor. Although age itself cannot be modified, our data highlights the need for more explicit risk counseling and information campaigns about the cardiovascular relevance of aging while focusing on measures to control coexisting modifiable risk factors.

Neuroendocrine circuitry and endometriosis: progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro.

Clinical symptoms of endometriosis, such as pain and infertility, can be described as persistent stressors. Such continuous exposure to stress may severely affect the equilibrium and bidirectional communication of the endocrine and immune system, hereby further aggravating the progression of endometriosis. In the present study, we aimed to tease apart mediators that are involved in the stress response as well as in the progression of endometriosis. Women undergoing diagnostic laparoscopy due to infertility were recruited (n = 69). Within this cohort, early stage of endometriosis were diagnosed in n = 30 and advanced stage of endometriosis in n = 8. Levels of progesterone in serum were determined. Frequency of progesterone receptor (PR) expression on CD56(+) and CD8(+) peritoneal lymphocytes was analysed by flow cytometry. The production of tumour necrosis factor (TNF) and interleukin (IL)-10 by peritoneal leukocytes upon stimulation with the potent stress mediator corticotropin-releasing hormone (CRH) and the progesterone derivative dydrogesterone, or both, were evaluated. Furthermore, the production of progesterone-induced blocking factor (PIBF) by peritoneal leukocytes and the expression of PR in endometriotic tissue were investigated. Levels of progesterone in serum were decreased in women with endometriosis and inversely correlated to pain scores. Furthermore, an increased frequency of CD56(+)PR(+) and CD8(+)PR(+) peritoneal lymphocytes was present in advanced endometriosis. The TNF/IL-10 ratio, reflecting cytokine secretion by peritoneal cells, was higher in cells derived from endometriosis patients and could be further heightened by CRH stimulation, whereas stimulation with dydrogesterone abrogated the CRH-mediated inflammation. Finally, the expression of PIBF by peritoneal leukocytes was increased in endometriosis. Low levels of progesterone in the follicular phase could be responsible for the progression of endometriosis and related pain. Peripheral CRH, increasing upon high psychological stress, might contribute to the peritoneal inflammation present in endometriosis. The therapeutic application of progesterone derivatives, CRH blocking agents as well as improvement of stress coping may disrupt the vicious circle between the chronic peritoneal inflammation and high perception of psychological stress in endometriosis.

Early risk factors for miscarriage: a prospective cohort study in pregnant women.

Many pregnancies are lost during early gestation, but clinicians still lack tools to recognize risk factors for miscarriage. Thus, the identification of risk factors for miscarriage during the first trimester in women with no obvious risk for a pregnancy loss was the aim of this prospective cohort trial. A total of 1098 women between gestation weeks 4 and 12 in whom no apparent signs of a threatened pregnancy could be diagnosed were recruited. Demographic, anamnestic, psychometric and biological data were documented at recruitment and pregnancy outcomes were registered subsequently. Among the cases with sufficiently available data, 809 successfully progressing pregnancies and 55 subsequent miscarriages were reported. In this cohort, risk of miscarriage was significantly increased in women at higher age (>33 years), lower body mass index (< or =20 kg/ m(2)) and lower serum progesterone concentrations (< or =12 ng/ml) prior to the onset of the miscarriage. Women with subsequent miscarriage also perceived higher levels of stress/demands (supported by higher concentrations of corticotrophin-releasing hormone) and revealed reduced concentrations of progesterone-induced blocking factor. These risk factors were even more pronounced in the subcohort of women (n = 335) recruited between gestation weeks 4 and 7. The identification of these risk factors and development of an interaction model of these factors, as introduced in this article, will help clinicians to recognize pregnant women who require extra monitoring and who might benefit from therapeutic interventions such as progestogen supplementation, especially during the first weeks of pregnancy, to prevent a miscarriage.

Immune status, psychosocial distress and reduced quality of life in infertile patients with endometriosis.

PROBLEM: The aim of the study was to identify if (i) psychosocial factors differ in endometriosis; (ii) related psychosocial aspects alter immune markers of depression/sickness behaviour; and (iii) serum immune marker may be indicative for endometriosis. METHOD OF STUDY: We enrolled 103 women in a case-control study. Psychosocial data were obtained, serum levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, interferon (IFN)-gamma, TNF-alpha, IFN-alpha and soluble intercellular adhesion molecule-1 (sICAM-1) were analysed. RESULTS: Among 69 eligible patients, endometriosis was diagnosed in 38 women. Patients with endometriosis reported reduced quality of life, increased stress perception/depressive symptoms; the Th1/Th2 ratio was in favour of Th1, accompanied by the increased levels of IFN-alpha. sICAM-1 levels were unaffected. No correlation could be confirmed between psychosocial and immune markers. CONCLUSION: Women with endometriosis may benefit from strategies contributing to reduction of stress and development of coping mechanisms, thus helping to break the vicious circle of inflammation, sickness behaviour and depression.