Bioimpedance cardiography in pregnancy: A longitudinal cohort study on hemodynamic pattern and outcome

Background: Pregnancy associated cardiovascular pathologies have a significant impact on outcome for mother and child. Bioimpedance cardiography may provide additional outcome-relevant information early in pregnancy and may also be used as a predictive instrument for pregnancy-associated diseases. Methods: We performed a prospective longitudinal cohort trial in an outpatient setting and included 242 pregnant women. Cardiac output and concomitant hemodynamic data were recorded from 11th-13th week of gestation every 5th week as well as at two occasions post partum employing bioimpedance cardiography. Results: Cardiac output increased during pregnancy and peaked early in the third trimester. A higher heart rate and a decreased systemic vascular resistance were accountable for the observed changes. Women who had a pregnancy-associated disease during a previous pregnancy or developed hypertension or preeclampsia had a significantly increased cardiac output early in pregnancy. Furthermore, an effect of cardiac output on birthweight was found in healthy pregnancies and could be confirmed with multiple linear regression analysis. Conclusions: Cardiovascular adaptation during pregnancy is characterized by distinct pattern described herein. These may be altered in women at risk for preeclampsia or reduced birthweigth. The assessment of cardiac parameters by bioimpedance cardiography could be performed at low costs without additional risks

The adipokine vaspin is associated with decreased coronary in-stent restenosis in vivo and inhibits migration of human coronary smooth muscle cells in vitro.

BACKGROUND:Percutaneous coronary intervention represents the most important treatment modality of coronary artery stenosis. In-stent restenosis (ISR) is still a limitation for the long-term outcome despite the introduction of drug eluting stents. It has been shown that adipokines directly influence vessel wall homeostasis by influencing the function of endothelial cells and arterial smooth muscle cells. Visceral adipose tissue-derived serpin vaspin was recently identified as a member of serine protease inhibitor family and serveral studies could demonstrate a relation to metabolic diseases. The aim of this study was to investigate a role of vaspin in the development of in-stent restenosis in vivo and on migration of smooth muscle cells and endothelial cells in vitro. METHODS:We studied 85 patients with stable coronary artery disease who underwent elective and successful PCI with implatation of drug eluting stents. Blood samples were taken directly before PCI. Vaspin plasma levels were measured by specific ELISA. ISR was evaluated eight months later by coronary angiography. Human coronary artery smooth muscle cells (HCASMC) and human umbilical vein endothelial cells (HUVEC) migration was analyzed by an in-vitro migration assay with different concentrations (0.004ng/mL up to 40ng/mL) of vaspin as well as by an scratch assay. For proliferation an impedance measurement with specialiced E-Plates was performed. RESULTS:During the follow up period, 14 patients developed ISR. Patients with ISR had significantly lower vaspin plasma levels compared to patients without ISR (0.213 ng/ml vs 0.382 ng/ml; p = 0.001). In patients with plasma vaspin levels above 1.35 ng/ml we could not observe any restenosis. There was also a significant correlation of plasma vaspin levels and late lumen loss in the stented coronary segments. Further we could demonstrate that vaspin nearly abolishes serum induced migration of HCASMC (100% vs. 9%; p<0.001) in a biphasic manner but not migration of HUVEC. Proliferation of HCASMC and HUVEC was not modulated by vaspin treatment. CONCLUSION:We were able to show that the adipokine vaspin selectively inhibits human coronary SMC migration in vitro and has no effect on HUVEC migration. Vaspin had no effect on proliferation of HUVEC which is an important process of the healing of the stented vessel. In addition, the occurrence of ISR after PCI with implantation of drug eluting stents was significantly associated with low vaspin plasma levels before intervention. Determination of vaspin plasma levels before PCI might be helpful in the identification of patients with high risk for development of ISR after stent implantation. In addition, the selective effects of vaspin on smooth muscle cell migration could potentially be used to reduce ISR without inhibition of re-endothelialization of the stented segment

Journal of Clinical Lipidology / Monocyte subset distribution in patients with stable atherosclerosis and elevated levels of lipoprotein(a)

Background Lipoprotein(a) (Lp(a)) is a proatherogenic plasma lipoprotein currently established as an independent risk factor for the development of atherosclerotic disease and as a predictor for acute thrombotic complications. In addition, Lp(a) is the major carrier of proinflammatory oxidized phospholipids (OxPL). Today, atherosclerosis is considered to be an inflammatory disease of the vessel wall in which monocytes and monocyte-derived macrophages are crucially involved. Circulating monocytes can be divided according to their surface expression pattern of CD14 and CD16 into at least 3 subsets with distinct inflammatory and atherogenic potential. Objective The aim of this study was to examine whether elevated levels of Lp(a) and OxPL on apolipoprotein B-100containing lipoproteins (OxPL/apoB) are associated with changes in monocyte subset distribution. Methods We included 90 patients with stable coronary artery disease. Lp(a) and OxPL/apoB were measured, and monocyte subsets were identified as classical monocytes (CMs; CD14++CD16), intermediate monocytes (IMs; CD14++CD16+), and nonclassical monocytes (NCMs; CD14+CD16++) by flow cytometry. Results In patients with elevated levels of Lp(a) (>50 mg/dL), monocyte subset distribution was skewed toward an increase in the proportion of IM (7.0 3.8% vs 5.2 3.0%; P = .026), whereas CM (82.6 6.5% vs 82.0 6.8%; P = .73) and NCM (10.5 5.3 vs 12.8 6.0; P = .10) were not significantly different. This association was independent of clinical risk factors, choice of statin treatment regime, and inflammatory markers. In addition, OxPL/apoB was higher in patients with elevated Lp(a) and correlated with IM but not CM and NCM. Conclusions In conclusion, we provide a potential link between elevated levels of Lp(a) and a proatherogenic distribution of monocyte subtypes in patients with stable atherosclerotic disease.(VLID)487417

PLOS One / Association of Small Dense LDL Serum Levels and Circulating Monocyte Subsets in Stable Coronary Artery Disease

Objective Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels. Methods We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel. Results Patients with sdLDL levels in the highest tertile (sdLDL4mg/dL;T3) showed the highest levels of pro-inflammatory NCM (15.27% vs. 11.46% and 10.94%, respectively; p<0.01) when compared with patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0-1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.28% vs. 83.97% and 82.75%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL levels (5.64% vs. 4.63% vs. 6.43% for T3, T2 and T1, respectively). In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels. Conclusion The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis.(VLID)491480

Multivariate Cox proportional hazards model assessing the association between G-CSF (below and above median) and major adverse cardiovascular events (death, myocardial infarction and rehospitalisation).

<p><b>-</b> denotes reference category.</p><p>Multivariate Cox proportional hazards model assessing the association between G-CSF (below and above median) and major adverse cardiovascular events (death, myocardial infarction and rehospitalisation).</p

Baseline characteristics of patients with and without combined endpoint during follow up period.

<p>Values are given as mean±SD or n (%); MACE: major adverse cardiovascular events (death, myocardial infarction, rehospitalisation); BMI: body mass index; MCI myocardial infarction.</p><p>Baseline characteristics of patients with and without combined endpoint during follow up period.</p

Cumulative CV event-free survival (all-cause death, myocardial infarction and rehospitalization; A) and cumulative survival (all-cause mortality; B) for patients with G-CSF below the median (green, dotted line) and above the median (red, full line).

<p>Cumulative CV event-free survival (all-cause death, myocardial infarction and rehospitalization; A) and cumulative survival (all-cause mortality; B) for patients with G-CSF below the median (green, dotted line) and above the median (red, full line).</p

Angiographical and interventional characteristics of patients with and without combined endpoint during follow-up period.

<p>MACE: major adverse cardiac cardiovascular events (death, myocardial infarction, rehospitalisation); CAD: coronary artery disease; BMS: bare metal stent; DES: drug eluting stent.</p><p>Angiographical and interventional characteristics of patients with and without combined endpoint during follow-up period.</p