PubMed · 11147282
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P Ohmans. 2000. Embracing diversity.. https://pubmed.ncbi.nlm.nih.gov/11147282/
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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.
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OBJECTIVES: We sought to determine the overall prognostic importance of left ventricular hypertrophy (LVH) among patients with coronary artery disease (CAD), as well as to determine whether this risk varies as a function of race or gender. BACKGROUND: Left ventricular hypertrophy is more prevalent among blacks and women than their counterparts. Blacks and women also have higher mortality with coronary disease. METHODS: We studied records of 2,461 patients (19% black, 42% women) diagnosed with CAD at cardiac catheterization between 1990 and 1998 from a single academic center. Left ventricular hypertrophy was defined using standard echocardiographic measures. Cox proportional hazards models were used for adjusted survival analyses. Mean patient follow-up was three years. RESULTS: Patients with LVH were older (68 vs. 65 years, p < 0.01), more often women (54% vs. 36%, p < 0.01), and black (25% vs. 16%, p < 0.01), and had higher unadjusted three-year mortality rates than patients without LVH (42% vs. 34%, p < 0.01). Left ventricular hypertrophy remained an independent predictor of mortality after adjusting for other clinical risk factors (hazard ratio 1.56, 95% confidence interval 1.35 to 1.80) with prognostic importance equivalent to that of left ventricular ejection fraction. Although the relative risk of LVH did not vary by race or gender, the attributable risk of LVH was greater in blacks and women. CONCLUSIONS: Clinicians should consider the prognostic importance of LVH when assessing risk in patients with CAD. Because LVH is more common among black and women patients with CAD, it partially accounts for racial and gender differences in survival.