N-terminal prohormone brain natriuretic peptide as a predictor of cardiovascular disease and mortality in blacks with hypertensive kidney disease: the African American Study of Kidney Disease and Hypertension (AASK).

BACKGROUND: Higher levels of N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular disease (CVD) in several disease states, but few data are available in patients with chronic kidney disease or in blacks. METHODS AND RESULTS: The African American Study of Kidney Disease and Hypertension trial enrolled hypertensive blacks with a glomerular filtration rate of 20 to 65 mL x min(-1) x 1.73 m(-2) and no other identified cause of kidney disease. NT-proBNP was measured with a sandwich chemiluminescence immunoassay (coefficient of variation 2.9%) in 994 African American Study of Kidney Disease and Hypertension participants. NT-proBNP was categorized as undetectable, low, moderate, or high. Proteinuria was defined as 24-hour urinary protein-creatinine ratio >0.22. A total of 134 first CVD events (CVD death or hospitalization for coronary artery disease, heart failure, or stroke) occurred over a median of 4.3 years. Participants with high NT-proBNP were much more likely to have a CVD event than participants with undetectable NT-proBNP after adjustment (relative hazard 4.0 [95% confidence interval [CI] 2.1 to 7.6]). A doubling of NT-proBNP was associated with a relative hazard of 1.3 (95% CI 1.0 to 1.6) for coronary artery disease, 1.7 (95% CI 1.4 to 2.2) for heart failure, 1.1 (95% CI 0.9 to 1.4) for stroke, and 1.8 (95% CI 1.4 to 2.4) for CVD death. The association of NT-proBNP with CVD events was significantly stronger (P(interaction)=0.05) in participants with than in those without proteinuria. Higher NT-proBNP was not associated with renal disease progression. CONCLUSIONS: These results suggest that elevated NT-proBNP levels are associated with higher CVD risk among blacks with hypertensive kidney disease. This association may be stronger in individuals with significant proteinuria.

Racial differences in ambulatory blood pressure and echocardiographic left ventricular geometry.

We examined the racial differences in left ventricular (LV) geometric pattern in relation to 24-hour ambulatory blood pressure (BP) monitoring and the presence or absence of a nocturnal BP dip. Our study confirms the blunting of nocturnal BP dip among black hypertensives. Body mass index, rather than race, was a major determinant of left ventricular hypertrophy. We did not observe a difference in prevalence of left ventricular hypertrophy by race. However, left ventricular adaptation to hypertension differed in hypertensive black and white individuals; whereas most of the white patients with Stage 1-2 hypertension had a normal ventricular pattern, LV concentric remodeling and concentric hypertrophy were the most common adaptive ventricular patterns in blacks with Stage 1-2 hypertension. A six-fold higher prevalence of concentric remodeling was observed in blacks as compared with whites. The impaired nocturnal BP dip in blacks may contribute to the different hemodynamic pattern. Determinants of myocardial oxygen consumption were significantly higher in black hypertensives.

Assessing medication adherence by pill count and electronic monitoring in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

The Medication Event Monitoring System (MEMS), an electronic monitor which records the date and time of bottle cap openings, and pill counts were used to assess patterns of adherence for the primary antihypertensive drug in the African American Study of Kidney Disease and Hypertension Pilot Study (AASK). Blacks with hypertension and moderately reduced renal function were randomized to one of two levels of blood pressure control and to one of three antihypertensive drug regimens: primary therapy with a calcium channel blocker, an angiotension converting enzyme inhibitor, or a beta-blocker. Of the 94 participants in AASK, 91 had MEMS recordings and pill counts for 313 regularly scheduled monthly follow-up visits. The average length of follow-up was 4.6 months. An acceptable level of adherence by pill count was achieved if 80% to 100% of the prescribed pills were not returned to the clinic. Adherence by MEMS to a once-a-day drug dosing schedule was acceptable if 80% of the time intervals between MEMS openings were within 24 +/- 6 h. Acceptable adherence by pill count was observed at 68% of the follow-up visits; MEMS indicated nonadherence at 47% of those visits. Blood pressure was within goal in 50% of the participants who were adherent by both pill count and MEMS throughout their follow-up visits, and only 14% of the participants who were identified nonadherent by one or both methods. These findings suggest that electronic monitoring is a useful adjunct to pill counts in assessing adherence to antihypertensive drugs. Feedback of electronically collected information on dosing intervals to participants and staff may enhance adherence.

Congenital cystic microphthalmia and consequent anophthalmia in the rat: a study in abnormal ocular morphogenesis.

An otherwise normal adult Charles River rat (CD strain) was observed to have no recognizable eyes. Breeding and morphological studies were undertaken to determine the nature of the ocular defect, as well as its cause and pathogenesis. The anomaly was found to be inherited as an autosomal recessive trait with variable expressivity. It was characterized by unilateral or bilateral congenital microphthalmia with multiple associated ocular abnormalities including a neuroepithelial cyst, optic nerve aplasia, and cataract. In several elderly rats, no eye was found histologically in the orbit, suggesting reabsorption of malformed tissues as the basis of the anophthalmia. Study of the prenatal morphogenesis of the microphthalmia suggested that the primary disorder reflects a disturbance of the neuroepithelium of the retinal anlage and results in defective early formation of the optic cup. The abnormalities in other ocular structures, particularly in the lens, are considered secondary. This ocular malformation emphasizes the early interactions and interdependence of the lens and retina in normal morphogenesis and provides an animal model for study of lens-retinal relationships in abnormal morphogenesis. It is particularly relevant in understanding the pathogenesis of microphthalmia with cysts in the human eye.

Epidermal protein synthesis in newborn rat skin.

Protein synthesis in newborn rat epidermis was assessed by in vivo labeling of epidermal proteins with radioactive glycine and the isolation of neutral buffer, sodium-dodecylsulfates (SDS) dithiothreitol soluble proteins, and 0.1 M NaOH soluble protein fractions of the epidermis. There was an increase in the labeling of proteins in the buffer and SDS fractions for 5 h after injection and then no further increase at 19 h after injection. In the 0.1 M NaOH soluble proteins and the final pellet after these extractions there was a progressive increase in glycine incorporation up to 19 h after injection. SDS gel electrophoresis of the labeled proteins showed early synthesis and continued synthesis of proteins of 56,000 and 65,000 daltons corresponding to the main fibrous proteins (alpha-keratins) of the epidermis. At 19 h a new protein band of 45,000 daltons first appeared and was associated with a decrease in the labeling of very high molecular weight (or highly aggregated) proteins. This later protein is presumptively identified as keratohyalin. Free amino acid pools were associated with both the neutral buffer and SDS extractable fractions.