PubMed · 462295
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J N de Klerk. 1979-04-28. Emigrant doctors.. https://pubmed.ncbi.nlm.nih.gov/462295/
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BACKGROUND: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca(2+) influx, which is controlled by the regulatory β₁-subunit (KCNMB1) of large-conductance heteromeric K+ ('BK') channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. METHODS: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). RESULTS: The 65Lys variant was relatively common, occurring on ∼5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for ∼0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for ∼0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for ∼0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). CONCLUSIONS: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease.
OBJECTIVE: To evaluate the influence of gender on the prognosis of coronary heart disease among black patients. DESIGN: Cohort study based on a consecutive sample from a hospital registry, with a mean follow-up of 4 years. SETTING: An inner-city public hospital in Chicago, Ill. PATIENTS: The study included 1719 consecutive black patients (780 men and 939 women) who had any one of the following events: cardiac catheterization for presumed coronary heart disease, hospitalization for acute myocardial infarction, or coronary artery bypass grafting. RESULTS: Hospital and operative mortality rates following acute myocardial infarction and coronary artery bypass grafting were similar between the two sexes. The relative risks for cardiac death in women vs men were 0.88 (95% confidence interval [CI], 0.60 to 1.28), 0.79 (95% CI, 0.53 to 1.17), and 0.79 (95% CI, 0.34 to 1.85) for coronary artery disease, acute myocardial infarction, and coronary artery bypass grafting, respectively, after adjusting for age, history of diabetes, hypertension, angina pectoris and myocardial infarction, number of diseased vessels, and ejection fraction. Compared with patients of the same sex with normal angiograms, relative risk estimates were 5.0, 10.1, and 6.3 for women and were 1.8, 4.0, and 2.0 for men in the same three groups of patients, respectively. CONCLUSIONS: Survival with coronary artery disease in black women is similar to that observed in black men, but relative to members of the same sex without the disease, the prognosis for women is considerably worse than for men.
The incidence of new coronary events and the predictive strength of the major coronary risk factors were evaluated in a biracial sample drawn from the general U.S. population. In this cohort of 12,599 persons, free of reported coronary heart disease (CHD) at baseline, both hospitalizations and deaths coded to this cause were recorded prospectively. Based on CHD as the underlying cause of death, black men and women experienced higher age-adjusted mortality than their white counterparts (BM = 6.15, WM = 5.59, BW = 3.72 and WW = 2.58 [cumulative deaths, percent]), while having lower hospitalization rates than did whites. In a univariate logistic regression model, with all incident events as the endpoint, the predictive strength of the coronary risk factors was remarkably similar for the four sex-race groups. Notable exceptions included smoking, where the data from this study are problematic, and body mass index, where a relationship was noted only among white women. In a multivariate model, the beta coefficients were similar for age, systolic blood pressure, cholesterol, and income; the statistical significance varied among the groups. Within the power of this study to examine between-race differences, the predictive strength of the standard risk factors are very similar. None of the within-sex, between-race differences in the multivariate relationships were significant, although sizable percentage differences were noted. Blacks appeared to receive less hospital care for CHD, despite higher rates of fetal events.