Gender Differences in Cardiovascular Health: Hormonal Effects on Cardiovascular Risk and Management.

Cardiovascular disease is the number one cause of death worldwide both in men and women. Significant differences however exist in the age of onset, type of cardiovascular disease (CVD), and treatment response among the genders. These differences are due to both gender societal effects and biological differences from the influence of the hormonal and metabolic milieu in the two sexes.Estrogens are the main female hormone. They impact signaling in almost every body organ and thus affect cardiovascular risk factors. These result in differential expression of CVD. The differential effect of treatment modalities is only recently being evaluated.Research is ongoing regarding the pathophysiology of these differences. Our current level of knowledge is described in this chapter.

Apparent Mineralocorticoid Excess in the Pediatric Population: Report of a Novel Pathogenic Variant of the 11ß-HSD2 Gene and Systematic Review of the Literature.

Apparent mineralocorticoid excess (AME) is a rare inherited disorder caused by pathogenic variants in the 11ß-HSD2 gene resulting in a deficiency of the 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme catalyzing the conversion of cortisol to its inactive metabolite, cortisone. Impaired cortisol metabolism results in a mineralocorticoid excess-like state presenting as low renin, low aldosterone hypertension (HTN) and hypokalemia. Typically, AME is diagnosed in early childhood. Medical treatment to control HTN and hypokalemia often is only partially successful. Herein, we systematically review previously reported AME cases in the pediatric population, focusing on presentation, genetic basis, treatment and outcomes. We demonstrate a negative correlation between the ratio of urinary cortisol to cortisone metabolites, and the age of diagnosis (p=0.0051). We also report a novel causative variant of the 11ß-HSD2 gene and propose an explanation for failure of the mineralocorticoid receptor antogonist, spironolactone, to control hypertension and hypokalemia in a subgroup of patients.

Utility of fetal echocardiography after normal cardiac imaging findings on detailed fetal anatomic ultrasonography.

OBJECTIVE: The purpose of this study was to assess the utility of fetal echocardiography (FE) after normal fetal cardiac imaging findings during detailed fetal anatomic ultrasonography (FAU). METHODS: We conducted a retrospective cohort review of obstetric ultrasonographic studies from November 2001 through July 2005. We identified women with a singleton gestation with increased risk for congenital heart disease who received FAU performed by a maternal-fetal medicine specialist at 16 to 20 weeks' gestation with subsequent FE. These records were compared with newborn outcomes. RESULTS: Of 789 pregnancies that had FAU and FE, 481 had satisfactory cardiac imaging. Of those, only 1 fetus had abnormal FE findings. After delivery, 4 of the 480 neonates with normal FAU and FE findings had a diagnosis of a heart defect. CONCLUSIONS: Fetal echocardiography does not substantially increase the detection rate of major cardiac anomalies after normal findings on detailed FAU performed by a maternal-fetal medicine specialist.

Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation.

OBJECTIVES: We studied the outcomes of pediatric patients diagnosed with dilated cardiomyopathy (DCM) and their relation to epidemiologic and echocardiographic variables at the time of presentation. BACKGROUND: The outcome of pediatric DCM patients ranges from recovery to a 50% to 60% chance of death within five years of diagnosis. The impact of heart transplantation and other emerging therapies on the outcomes of pediatric DCM patients is uncertain. METHODS: We performed a retrospective study of the outcomes in 91 pediatric patients diagnosed with DCM from 1990 to 1999. Routine therapy included use of digoxin, diuretics, angiotensin-converting enzyme inhibitors, and heart transplantation. RESULTS: At the time of last follow-up, 11 patients (12%) had died without transplantation; 20 (22%) underwent transplantation; 27 (30%) had persistent cardiomyopathy; and 33 (36%) had recovery of left ventricular systolic function. Overall actuarial one-year survival was 90%, and five-year survival was 83%. However, actuarial freedom from "heart death" (death or transplantation) was only 70% at one year and 58% at five years. Multivariate analysis found age <1 year (hazard ratio 7.1), age >12 years (hazard ratio 4.5), and female gender (hazard ratio 3.0) to be significantly associated with a greater risk of death or transplantation and a higher left ventricular shortening fraction at presentation (hazard ratio 0.92), with a slightly decreased risk of death or transplantation. CONCLUSIONS: Pediatric DCM patients continue to have multiple outcomes, with recovery of left ventricular systolic function occurring most frequently. Utilization of heart transplantation has led to improved survival after the diagnosis of pediatric DCM.

Pediatric cardiac transplantation.

Pediatric cardiac transplant patients present many challenges to the medical community. These include such things as complex evaluations, preoperative heart failure support, complex operative interventions, and postoperative challenges in management. In spite of these challenges, survival outcomes for children undergoing a heart transplant have improved dramatically over the last two decades.

Protective role of tuftsin fragment 1-3 in an animal model of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) causes morbidity and mortality and commonly follows the reperfusion after an ischemic event. Tissue plasminogen activator (tPA), a fibrinolytic serine protease, is routinely given for the treatment of stroke. However, tPA also can promote neuronal death, suggesting that caution should be exercised when using it. Furthermore, tPA upon brain injury mediates microglial activation and modulates neuronal survival. To investigate the role of tPA and microglia during brain hemorrhage, we induced experimentally ICH by intracerebral injection of collagenase. Seven days after the introduction of ICH, it persisted in tPA-deficient (tPA(-/-)) mice but is drastically reduced in size in wild-type mice. Three weeks after ICH, there are still red blood cells in tPA(-/-) but not in wild-type animals. Activated microglia persist around the injury site. When microglial activation is inhibited by tuftsin fragment 1-3 macrophage/microglial inhibitory factor (MIF), the stroke injury volume is significantly reduced, and the neurobehavioral deficits exhibited by the mice are improved. Our results suggest that endogenous tPA assists in the clearance of intracerebral hemorrhage, presumably by affecting microglial activation, and MIF could be a valuable neuroprotective agent for the treatment of ICH.