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June 2008

Editor:
Michael Bissell, MD, PhD, MPH

Cervical hCG concentration and risk of reterm delivery
C-reactive protein and insulin resistance as risk factors for poor prognosis after heart transplantation
A predictive marker for metabolic syndrome

Cervical hCG concentration and risk of reterm delivery Cervical hCG concentration and risk of reterm delivery

The authors conducted a pros­pective study to determine the correlation between cervical human chorionic gonadotropin concentration and duration of pregnancy. The study involved 150 women who were between the 24th and 34th weeks of a singleton pregnancy and had symptoms suggestive of preterm labor. The inclusion criteria were four regular uterine contractions per 20-min. intervals accompanied by low back pain or low abdominal pain, pelvic pressure, and increased vaginal discharge. Exclusion criteria were ruptured membranes, vaginal bleeding, cervical dilatation of 4 cm or more, cervical cerclage in the present pregnancy, placenta previa, a history of trauma and tocolysis, preeclampsia, and fever (body temperature higher than 37.8°C). Of the study group, 71 women (47.3%) delivered after 37 weeks of pregnancy (group at term) and 79 (52.7%) delivered before 37 weeks of pregnancy (preterm group). After a sample of cervicovaginal secretions was obtained, the levels of human chorionic gonadotropin (hCG) in the secretions were measured by immunoassay and compared between the two groups. The mean ± SD pregnancy duration was 32.42±2.01 weeks at the time of sampling and 35.83±2.88 weeks at the time of delivery; the means for cervical dilatation and effacement were 1.74±0.8 cm and 30.61 percent±15.82 percent, respectively; and the mean overall hCG concentration in the cervico­vaginal secretions at the time of sampling was 35.93±59.97 mIU/mL. The mean hCG concentration was 7.9±34.1 mIU/mL in the group at term and 61.12±66.84 mIU/mL in the preterm group, and the difference was statistically significant (P<.001). Moreover, a significant positive correlation was noted between cervical hCG concentration and pregnancy duration at the time of sampling (P<.01; r=0.2), cervical dilatation (P<.001; r=0.54), and cervical effacement (P<.001; r=0.43). A significant negative correlation was noted between hCG concentration and pregnancy duration at delivery (P<.001; r=–0.4). A regression model was used to analyze age, gravidity, parity, history of abortion, pregnancy duration at the time of sampling, pregnancy duration at delivery, cervical dilatation, effacement, and hCG concentration in the cervical secretions. Only cervical dilatation (P<.01; r=0.2), pregnancy duration at the time of sampling (P<.001, r=0.22), and pregnancy duration at the time of delivery (P<.001; r=–0.74) were found to be correlated with hCG concentration in the cervicovaginal secretions. The authors concluded that the best sensitivity and specificity correspond to a concentration of 9.5 mIU/mL (sensitivity, 92.4% [95% confidence interval, 83.6–96.9%]; specificity, 87.3% [95% CI, 76.8–93.7%]; positive predictive value, 89 percent of women). This may be a natural protective measure, as estrogen is a better antioxidant than glutathione (GSH). Therefore, this study suggests that ovaries retain some function even after menopause and probably can increase their estrogen production in instances of stress.

Kashanian M, Asl MM, Zadeh JK. Human chorionic gonadotropin in cervicovaginal secretion as a predictor of preterm delivery. J Gynecol Obstet. 2007;97:44–51.

Reprints: M. Kashanian, Khajeh Nasir Toosi Ave., Mostaghimi Alley, No. 83, Postal Code 16117, Tehran, Iran; maryamkashanian@yahoo.com

C-reactive protein and insulin resistance as risk factors for poor prognosis after heart transplantation C-reactive protein and insulin resistance as risk factors for poor prognosis after heart transplantation

The pathogenesis of cardiac allograft vasculopathy, a major cause of death in patients surviving more than one year after heart transplantation, involves several immunologic and metabolic factors. Among them are ischemia-reperfusion injury, human leukocyte antigen mismatch, viral infection, hyperlipemia, and hypertension. In addition to these well-known risk factors, the authors showed that markers of dysmetabolic syndrome are associated with increased incidence of cardiac allograft vasculopathy (CAV) and poor prognosis after heart transplantation. Systemic inflammation is believed to represent an important mechanistic pathway through which metabolic risk factors may lead to vascular disease. The authors conducted a study for which they hypothesized that an active interplay between systemic inflammation and markers of metabolic dysregulation may increase the risk for CAV and subsequently worsen cardiovascular prognosis. In particular, metabolic dysregulation was assessed using the ratio between the serum concentration of triglycerides and high-density lipoproteins (TG/HDL), which has been proposed as an indirect and widely available marker of insulin resistance, and C-reactive protein (CRP) was chosen as a marker of systemic inflammation. CRP and the entire metabolic panel were evaluated in 98 consecutive heart transplant recipients at the time of annual coronary angiography, 5.8 years after transplant (range, 1 to 12 years). A ratio of triglycerides to high-density lipoproteins of 3.0 or more was considered a marker of insulin resistance. Prevalence of CAV was defined by angiography, and subsequent prognosis was evaluated as incidence of major cardiac adverse events. CRP was higher in the 34 patients with angiographic CAV than in those without CAV (1.10±0.20 versus 0.50±0.05 mg/dL; P<.001). Patients with insulin resistance had higher CRP concentrations (P=.023) and higher CAV prevalence (P=.005). High CRP and a TG/HDL of 3.0 or more were independently associated with an increased likelihood of CAV (odds ratio, =3.9; P=.02) and predicted an increased risk of major cardiac adverse events. The combination of high CRP and a TG/HDL of 3.0 or more identified a subgroup of patients having a four-fold increased risk for CAV and a three-fold increased risk for major cardiac adverse events compared with patients with low CRP and normal values for metabolic indicators. The authors concluded that CRP and insulin resistance, as estimated by TG/HDL, appear to be strong, synergic risk factors for CAV and for major cardiac adverse events. These findings support the hypothesis that in heart transplant recipients, systemic inflammation may be an important mediator of graft vascular injury associated with metabolic syndrome.

Biadi O, Potena L, Fearon WF, et al. Interplay between systemic inflammation and markers of insulin resistance in cardiovascular prognosis after heart transplantation. J Heart Lung Transplant. 2007; 26: 324– 330.

Reprints: Dr. Hannah A. Valantine, Falk Cardiovascular Research Center, 300 Pasteur Drive, Stanford University, Stanford, CA 94305; hvalantine@ stanford.edu

A predictive marker for metabolic syndrome A predictive marker for metabolic syndrome

Metabolic syndrome encompasses a cluster of interrelated risk factors that are closely associated with the development of atherosclerotic cardiovascular diseases. Obesity, especially excessive accumulation of abdominal fat, is the principal etiological factor that predisposes to insulin resistance and metabolic syndrome (MetS). Obesity triggers metabolic stress and inflammatory responses in adipose tissue, both of which are considered to be important mediators of obesity-related metabolic and cardiovascular pathologies. Adipocyte-fatty acid binding protein (A-FABP; also designated aP2 or FABP4) is an ˜15-kDa, small, lipid-binding protein that is expressed predominantly in adipose tissue. This protein is the major cytosolic protein of mature adipocytes, accounting for approximately six percent of the total cellular protein. In addition, A-FABP is present in macro­phages, which have striking similarities to adipocytes in biology and function. Mounting evidence suggests that this protein plays a key role in linking obesity with various features of MetS. To further evaluate whether A-FABP is an independent risk factor for the cluster of metabolic risk factors that predispose to atherosclerotic cardiovascular disease, the authors investigated prospectively the five-year development of MetS in relation to baseline A-FABP levels in a population-based cohort of 495 Chinese subjects recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study. At baseline, high A-FABP levels were associated with MetS (odds ratio, 4.0; 95% confidence interval, 1.5–10.4; highest versus lowest sex-specific tertile, adjusted for age, body mass index, homeostasis model assessment index for insulin resistance, C-reactive protein, and adiponectin, P=.005). On long-term followup, subjects with higher baseline A-FABP levels had a progressively worse cardiometabolic risk profile and increased risk of MetS. Fifty of the 376 subjects without MetS at baseline developed it at five years. Apart from the homeostasis model assessment index for insulin resistance (P=.001), baseline A-FABP was the only independent predictor of the development of MetS during the five-year followup (odds ratio, 4.7; 95% CI, 1.8–11.9; highest versus lowest sex-specific tertile, P=.001, adjusted for the homeostasis model assessment index for insulin resistance and body mass index). A-FABP was predictive of MetS even after adjusting for each of its individual components. The authors concluded that circulating A-FABP predicts the development of MetS independently of adiposity and insulin resistance.

Xu A, Tso AWK, Cheung BMY, et al. Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation. 2007;115:1537–1543.

Reprints: Dr. Karen Lam, Dept. of Medicine, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd., Hong Kong, China; ksllam@hkucc.hku.hk


Dr. Bissell is Professor and Director of Clinical Services and Vice Chair, Department of Pathology, Ohio State University Medical Center, Columbus.