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J Coresh

Publications and source records attributed to J Coresh.

At least 19 recordsLinked to original sources
PubMed2006

Three single-nucleotide polymorphisms in LPA account for most of the increase in lipoprotein(a) level elevation in African Americans compared with European Americans.

BACKGROUND: The extent which universally common or population-specific alleles can explain between-population variations in phenotypes is unknown. The heritable coronary heart disease risk factor lipoprotein(a) (Lp(a)) level provides a useful case study of between-population variation, as the aetiology of twofold higher Lp(a) levels in African populations compared with non-African populations is unknown. OBJECTIVE: To evaluate the association between LPA sequence variations and Lp(a) in European Americans and African Americans and to determine the extent to which LPA sequence variations can account for between-population variations in Lp(a). METHODS: Serum Lp(a) and isoform measurements were examined in 534 European Americans and 249 African Americans from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Study. In addition, 12 LPA variants were genotyped, including 8 previously reported LPA variants with a frequency of >2% in European Americans or African Americans, and four new variants. RESULTS: Isoform-adjusted Lp(a) level was 2.23-fold higher among African Americans. Three single-nucleotide polymorphisms (SNPs) were independently associated with Lp(a) level (p<0.02 in both populations). The Lp(a)-increasing SNP (G-21A, which increases promoter activity) was more common in African Americans, whereas the Lp(a)-lowering SNPs (T3888P and G+1/inKIV-8A, which inhibit Lp(a) assembly) were more common in European Americans, but all had a frequency of <20% in one or both populations. Together, they reduced the isoform-adjusted African American Lp(a) increase from 2.23 to 1.37-fold(a 60% reduction) and the between-population Lp(a) variance from 5.5% to 0.5%. CONCLUSIONS: Multiple low-prevalence alleles in LPA can account for the large between-population difference in serum Lp(a) levels between European Americans and African Americans.

Adolescent↗
PubMed2006

Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: a longitudinal study.

Elevated bone mineral parameters have been associated with mortality in dialysis patients. There are conflicting data about calcium, parathyroid hormone (PTH), and mortality and few data about changes in bone mineral parameters over time. We conducted a prospective cohort study of 1007 incident hemodialysis and peritoneal dialysis patients. We examined longitudinal changes in bone mineral parameters and whether their associations with mortality were independent of time on dialysis, inflammation, and comorbidity. Serum calcium, phosphate, and calcium-phosphate product (CaP) increased in these patients between baseline and 6 months (P<0.001) and then remained stable. Serum PTH decreased over the first year (P<0.001). In Cox proportional hazards models adjusting for inflammation, comorbidity, and other confounders, the highest quartile of phosphate was associated with a hazard ratio (HR) of 1.57 (1.07-2.30) using both baseline and time-dependent values. The highest quartiles of calcium, CaP, and PTH were associated with mortality in time-dependent models but not in those using baseline values. The lowest quartile of PTH was associated with an HR of 0.65 (0.44-0.98) in the time-dependent model with 6-month lag analysis. We conclude that high levels of phosphate both at baseline and over follow-up are associated with mortality in incident dialysis patients. High levels of calcium, CaP, and PTH are associated with mortality immediately preceding an event. Promising new interventions need to be rigorously tested in clinical trials for their ability to achieve normalization of bone mineral parameters and reduce deaths of dialysis patients.

Adult↗
PubMed2005

Stability of haemoglobin A1c (HbA1c) measurements from frozen whole blood samples stored for over a decade.

OBJECTIVE: Haemoglobin A1c (HbA1c), a measure of long-term glycaemic control, is at the centre of the clinical management of diabetes mellitus. However, the reproducibility of HbA1c measurements from whole blood samples which have been in long-term storage is unknown. We undertook this study to assess the reproducibility of HbA1c measurements from whole blood samples that had been in storage at -70 degrees C for over a decade. RESEARCH DESIGN AND METHODS: Three hundred and thirty-six samples of frozen whole blood from the Atherosclerosis Risk in Communities (ARIC) Study, stored at -70 degrees C for 11-14 years assayed for HbA1c using a dedicated ion-exchange HPLC assay (Tosoh A1c 2.2 Plus HPLC) were compared with measurements on these same samples conducted prior to storage (in 1990-92) using a Diamat (Bio-Rad) HPLC instrument. RESULTS: HbA1c measurements from long-term stored samples were strongly correlated with values obtained prior to long-term storage (r=0.97). The difference between HbA1c from long- and short-term stored samples had a mean of 0.35% HbA1c (sd=0.35) and a CV of 5.8%, which was approximately three times that of duplicate assays (CV 1.3 to 2.5%). CONCLUSIONS: These data demonstrate that highly correlated but more variable and slightly higher HbA1c results were obtained from frozen whole blood samples that have been in storage for more than a decade. This highly reproducible assay performance would lead to comparable ranking of individuals and unbiased estimates of relative risks and odds ratios in epidemiological studies (case-control and cohort designs), but results should be realigned when the absolute value is of interest. These results have important implications for epidemiological studies and clinical trials which have stored whole blood specimens.

Biomarkers↗
PubMed2004

Undertreatment of hyperlipidemia in a cohort of United States kidney dialysis patients.

BACKGROUND: Application of national guidelines regarding cardiovascular disease risk reduction to kidney dialysis patients is complicated by the conflicting observations that dialysis patients have a high risk of atherosclerotic cardiovascular disease (ASCVD), but dialysis patients with higher serum cholesterol have lower mortality rates. Actual treatment patterns of hyperlipidemia are not well studied. METHODS: We assessed the prevalence, treatment and control of hyperlipidemia in this high-risk patient population from 1995 - 1998. We measured low-density lipoprotein cholesterol, treatment with a lipid-lowering agent, and prevalence of hyperlipidemia as defined by the National Cholesterol Education Program (NCEP), Adult Treatment Panel (ATP) II guidelines in 812 incident hemodialysis (HD), and peritoneal dialysis (PD) patients from dialysis clinics in 19 states throughout the United States. RESULTS: Hyperlipidemia was present in 40% of HD and 62% of PD patients. Among subjects with hyperlipidemia, 67% of HD and 63% of PD patients were untreated and only 22% of HD and 14% of PD patients were treated and controlled. Those who entered the study in 1997 or 1998, those with diabetes, males and Caucasians were more likely to be treated and controlled, whereas subjects on PD and those with ASCVD were less likely to be treated and controlled. CONCLUSION: These data suggest that high rates of undertreatment exist in the United States ESRD dialysis population. Whether improved rates of treatment will result in decreased cardiovascular disease events needs to be tested in randomized clinical trials.

Cardiovascular Diseases↗
PubMed2001

Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994).

BACKGROUND: The prevalence and incidence of end-stage renal disease in the United States are increasing, but milder renal disease is much more common and may often go undiagnosed and undertreated. METHODS: A cross-sectional study of a representative sample of the US population was conducted using 16 589 adult participants aged 17 years and older in the Third National Health and Nutrition Examination Survey (NHANES III) conducted from 1988 to 1994. An elevated serum creatinine level was defined as 141 micromol/L or higher (>/=1.6 mg/dL) for men and 124 micromol/L or higher (>/=1.4 mg/dL) for women (>99th percentile for healthy young adults) and was the main outcome measure. RESULTS: Higher systolic and diastolic blood pressures, presence of hypertension, antihypertensive medication use, older age, and diabetes mellitus were all associated with higher serum creatinine levels. An estimated 3.0% (5.6 million) of the civilian, noninstitutionalized US population had elevated serum creatinine levels, 70% of whom were hypertensive. Among hypertensive individuals with an elevated serum creatinine level, 75% received treatment. However, only 11% of all individuals with hypertension had their blood pressure reduced to lower than 130/85 mm Hg (the Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommendation for hypertensive individuals with renal disease); 27% had a blood pressure lower than 140/90 mm Hg. Treated hypertensive individuals with an elevated creatinine level had a mean blood pressure of 147/77 mm Hg, 48% of whom were prescribed one antihypertensive medication. CONCLUSION: Elevated serum creatinine level, an indicator of chronic renal disease, is common and strongly related to inadequate treatment of high blood pressure.

Adolescent↗
PubMed2001

Associations of tibia lead, DMSA-chelatable lead, and blood lead with measures of peripheral nervous system function in former organolead manufacturing workers.

BACKGROUND: The goals of the present study were to compare and contrast associations of blood lead, DMSA-chelatable lead, current tibia lead, and back-extrapolated "peak" tibia lead with four peripheral nervous system (PNS) sensory and motor function measures in older males with past exposure to organic and inorganic lead. METHODS: Data were collected from former organolead manufacturing workers with an average of 16 years since last occupational lead exposure. Current tibia lead levels were measured by (109)Cd x-ray fluorescence. Sensory pressure thresholds (index and pinky fingers) and pinch and grip strength were measured with the Pressure-Specified Sensory Device (PSSD). RESULTS: In adjusted analyses, none of the four lead biomarkers was associated with sensory pressure threshold of the index finger or pinch or grip strength. In contrast, all four biomarkers were associated (P < or = 0.10) with pressure threshold of the pinky finger. The final linear regression models accounted for a small proportion of the variance in the sensory (1-3%) and motor measures (10-21%). CONCLUSIONS: This study found no strong association between lead biomarkers and selected PNS sensory or motor function measures among former organolead manufacturing workers with no recent occupational exposure to lead. Previously reported CNS findings in this cohort suggest that the PNS may be less sensitive to the chronic toxic effects of lead in this dose range among adults. It is also possible that the PNS has a greater capacity for repair than does the CNS, or that the PNS measures were less sensitive for detection of lead-related health outcomes than were the CNS measures.

Adult↗
PubMed2001

Timing of nephrologist referral and arteriovenous access use: the CHOICE Study.

Recent clinical practice guidelines recommend the creation of an arteriovenous (AV) vascular access (ie, native fistula or synthetic graft) before the start of chronic hemodialysis therapy to prevent the need for complication-prone dialysis catheters. We report on the association of referral to a nephrologist with duration of dialysis-catheter use and type of vascular access used in the first 6 months of hemodialysis therapy. The study population is a representative cohort of 356 patients with questionnaire, laboratory, and medical record data collected as part of the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Center Study. Patients who reported being seen by a nephrologist at least 1 month before starting hemodialysis therapy (75%) were more likely than those referred later to use an AV access at initiation (39% versus 10%; P < 0.001) and 6 months after starting hemodialysis therapy (74% versus 56%; P < 0.01). Patients referred within 1 month of initiating hemodialysis therapy used a dialysis catheter for a median of 202 days compared with 64, 67, and 19 days for patients referred 1 to 4, 4 to 12, and greater than 12 months before initiating hemodialysis therapy, respectively (P trend < 0.001). Patients referred at least 4 months before initiating hemodialysis therapy were more likely than patients referred later to use an AV fistula, rather than a synthetic graft, as their first AV access (45% versus 31%; P < 0.01). These associations remained after adjustment for age, sex, race, marital status, education, insurance coverage, comorbid disease status, albumin level, body mass index, and underlying renal diagnosis. These data show that late referral to a nephrologist substantially increases the likelihood of dialysis-catheter use at the initiation of hemodialysis therapy and is associated with prolonged catheter use. Regardless of the time of referral, only a minority of patients used an AV access at the initiation of treatment, and greater than 25% had not used an AV access 6 months after initiation. Thus, further efforts to improve both referral patterns and preparation for dialysis after referral are needed.

Adolescent↗
PubMed2000

Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years.

BACKGROUND: The benefit of intravenous thrombolytic therapy in elderly patients with myocardial infarction is uncertain. There are no randomized trials of thrombolytic efficacy or observational studies of clinical effectiveness that focus specifically on the elderly. METHODS AND RESULTS: To determine whether thrombolytic therapy for elderly patients is associated with a survival advantage in a large observational database, we conducted a retrospective cohort study of 7864 Medicare fee-for-service patients aged 65 to 86 years with the primary discharge diagnosis of acute myocardial infarction who were admitted with clinical and ECG indications for thrombolytic therapy and no absolute contraindications. The study included all US acute care nongovernment hospitals without on-site angioplasty capability. Using proportional-hazards methods, we found that in a comprehensive multivariate model, there was a significant interaction (P<0.001) between age and the effect of thrombolytic therapy on 30-day mortality rates. For patients 65 to 75 years old, thrombolytic therapy was associated with a survival benefit, consistent with randomized trials. Among patients aged 76 to 86 years, thrombolytic therapy was associated with a survival disadvantage, with a 30-day mortality hazard ratio of 1.38 (95% CI 1. 12 to 1.71, P=0.003). For these patients, there was no benefit from thrombolytic therapy in any clinical subgroup. CONCLUSIONS: In nationwide clinical practice, thrombolytic therapy for patients >75 years old is unlikely to confer survival benefit and may have a significant survival disadvantage. Reperfusion research that is focused on elderly patients is urgently needed.

Aged↗
PubMed2000

Randomized double-blind trial of oral essential amino acids for dialysis-associated hypoalbuminemia.

BACKGROUND: Hypoalbuminemia is associated with substantial morbidity and mortality in dialysis patients. METHODS: Subjects with a mean three-month prestudy serum albumin of 3.8 g/dL or less and who demonstrated >/=90% compliance during a two-week run-in period were randomized to 3.6 g of essential amino acids (EAAs) or placebo three times daily with meals for three months. Randomization was stratified by dialysis modality and by severity of the hypoalbuminemia. The primary study outcome was change in the average of three monthly serum albumin measurements between baseline and follow-up. RESULTS: Fifty-two patients were randomized; 47 patients (29 hemodialysis and 18 peritoneal dialysis) met the predetermined primary analysis criteria. The mean compliance rates averaged 75, 70, and 50% at months 1, 2, and 3, respectively, and were similar for EAAs and placebo. Serum albumin in the hemodialysis patients, EAA versus placebo, improved [(mean +/- SE) 0.22 +/- 0.09 g/dL, P = 0.02]. Changes in peritoneal dialysis patients were not significant (0.01 +/- 0.15 g/dL), but approached significance for the total study group (0.14 +/- 0.08 g/dL, P = 0.08). Patients in the very low albumin strata (<3.5 g/dL) improved more than those in the low albumin strata (3.5 to 3.8 g/dL, P < 0.01). There was a significant correlation (r = 0.83, P = 0.001) within the hemodialysis EAA group between the baseline C-reactive protein level and improvement in serum albumin. Improvements were also seen in grip strength and SF-12 mental health score, but not in serum amino acid levels, SF-12 physical health score, or anthropometric measurements. CONCLUSIONS: Oral EAAs induce a significant improvement in the serum albumin concentration in hemodialysis but not peritoneal dialysis subjects. Further study of their long-term effects on morbidity and mortality is warranted.

Administration, Oral↗
PubMed2000

Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study.

BACKGROUND: Animal and in vitro data suggest that dyslipidemia plays an important role in the initiation and progression of chronic renal disease, but few prospective studies have been conducted in humans. METHODS: We studied the relationship of plasma lipids to a rise in serum creatinine of 0.4 mg/dL or greater in 12,728 Atherosclerosis Risk in Communities (ARIC) participants with baseline serum creatinine that was less than 2.0 mg/dL in men and less than 1.8 mg/dL in women. RESULTS: During a mean follow-up of 2.9 years, 191 persons had a rise in creatinine of 0.4 mg/dL or greater, yielding an incidence rate of 5.1 per 1000 person years. Individuals with higher triglycerides and lower high-density lipoprotein (HDL) and HDL-2 cholesterol at baseline were at increased risk for a rise in creatinine after adjustment for race, gender, baseline age, diabetes, serum creatinine, systolic blood pressure, and antihypertensive medication use (all P trends </=0.02). The adjusted relative risk for the highest versus lowest quartile of triglycerides was 1.65 (95% CI, 1.1, 2.5, P = 0.01) and for HDL was 0.47 (95% CI, 0.3, 0.8, P = 0.003). These associations were significant in participants with normal creatinine (defined as <1.4 mg/dL for men and <1.2 mg/dL for women), with diabetes, and without diabetes. The effect of high triglycerides was independent of plasma glucose, but was weaker and less consistent after further adjustment for fasting insulin in nondiabetics. CONCLUSIONS: High triglycerides and low HDL cholesterol, but not low-density lipoprotein cholesterol, predict an increased risk of renal dysfunction. The treatment of these lipid abnormalities may decrease the incidence of early renal disease.

Arteriosclerosis↗
PubMed2000

Relation between gender and vascular access complications in hemodialysis patients.

Native arteriovenous (AV) fistulae for hemodialysis vascular access are believed to be associated with fewer complications than synthetic polytetrafluoroethylene (PTFE) grafts. We conducted a study among patients in the Dialysis Morbidity and Mortality Study to compare risk factors for complications of AV fistulae and PTFE grafts in men and women and to examine the effect of age on vascular access complications. We analyzed data from 833 incident patients with end-stage renal disease who had a PTFE graft (n = 621) or AV fistula (n = 212) in use 1 month after starting hemodialysis therapy. Follow-up using inpatient and outpatient Medicare administrative data identified a 1.8-times greater risk for a subsequent vascular access procedure for PTFE grafts (0.71 procedures/access-year) than for AV fistulae (0.39 procedures/access-year). Men with grafts and women with grafts or fistulae had a greater risk for a first subsequent access procedure than did men with fistulae (0.79, 0.65, and 0.59 versus 0.33 procedures/access-year, respectively). After adjustment for age, race, presence of diabetes mellitus, and history of smoking, peripheral vascular disease, and cardiovascular disease, use of a PTFE graft compared with an AV fistula was associated with a greater risk for a first subsequent procedure in men (relative hazard, 2.2; 95% confidence interval [CI], 1.6 to 2.9), but not in women (relative hazard, 1.0; 95% CI, 0.7 to 1.4). The excess risk associated with a PTFE graft compared with an AV fistula was limited to men in the lower three quartiles of age (ie, </=72 years). These data raise concern that the potential benefits of AV fistulae over PTFE grafts are not realized in women and older men. A better understanding of the determinants of successful access maturation and maintenance in these groups is needed.

Age Factors↗
PubMed2000

Relationship between skin color and blood pressure in egyptian adults: results from the national hypertension project.

In many, but not all societies, dark skin color is associated with high blood pressure. Whether the association between skin color and blood pressure is independent of known determinants of blood pressure remains controversial. We examined the association between skin color and blood pressure in 835 Egyptian adults (370 men and 465 women) participating in the National Hypertension Project, a national survey of hypertension prevalence and blood pressure-related complications conducted in Egypt during 1991-1993. Skin color was assessed by measuring the concentration of cutaneous melanin in an unexposed area with the use of reflectance spectrophotometry. Higher concentrations of melanin were associated with lower body mass index, less education, manual labor (among men), and a lower urinary sodium-to-potassium ratio (among women). In multivariate regression analyses adjusted for age, body mass index, and education, there was a significant nonlinear association between blood pressure and skin color among women; in the lower to intermediate range of skin pigmentation, both systolic and diastolic blood pressures were higher in women with greater concentrations of cutaneous melanin. In men, blood pressure was not associated with skin color. When we used a subjective assessment of skin color, there was no significant difference in blood pressure between black-skinned Egyptians (predominantly of Nubian descent) and fair-skinned Egyptians for either gender. While the significant relationship in women appeared to be independent of known risk factors for hypertension, residual confounding may explain the association.

Adult↗
PubMed1999

The association between hospital volume and survival after acute myocardial infarction in elderly patients.

BACKGROUND: Patients with chest pain thought to be due to acute coronary ischemia are typically taken by ambulance to the nearest hospital. The potential benefit of field triage directly to a hospital that treats a large number of patients with myocardial infarction is unknown. METHODS: We conducted a retrospective cohort study of the relation between the number of Medicare patients with myocardial infarction that each hospital in the study treated (hospital volume) and long-term survival among 98,898 Medicare patients 65 years of age or older. We used proportional-hazards methods to adjust for clinical, demographic, and health-system-related variables, including the availability of invasive procedures, the specialty of the attending physician, and the area of residence of the patient (rural, urban, or metropolitan). RESULTS: The patients in the quartile admitted to hospitals with the lowest volume were 17 percent more likely to die within 30 days after admission than patients in the quartile admitted to hospitals with the highest volume (hazard ratio, 1.17; 95 percent confidence interval, 1.09 to 1.26; P<0.001), which resulted in 2.3 more deaths per 100 patients. The crude mortality rate at one year was 29.8 percent among the patients admitted to the lowest-volume hospitals, as compared with 27.0 percent among those admitted to the highest-volume hospitals. There was a continuous inverse dose-response relation between hospital volume and the risk of death. In an analysis of subgroups defined according to age, history of cardiac disease, Killip class of infarction, presence or absence of contraindications to thrombolytic therapy, and time from the onset of symptoms, survival at high-volume hospitals was consistently better than at low-volume hospitals. The availability of technology for angioplasty and bypass surgery was not independently associated with overall mortality. CONCLUSIONS: Patients with acute myocardial infarction who are admitted directly to hospitals that have more experience treating myocardial infarction, as reflected by their case volume, are more likely to survive than are patients admitted to low-volume hospitals.

Aged↗
PubMed1999

Use of cardiovascular procedures among black persons and white persons: a 7-year nationwide study in patients with renal disease.

BACKGROUND: Black persons historically undergo fewer invasive cardiovascular procedures than white persons. OBJECTIVE: To determine whether acquisition of Medicare health insurance and comprehensive care for severe illness reduce ethnic disparity in use of cardiovascular procedures. DESIGN: 7-year longitudinal analyses in a cohort from the United States Renal Data System. SETTING: Health care institutions in the United States. PATIENTS: Nationwide random sample of 4987 adult black and white patients with incident end-stage renal disease (ESRD) from 303 dialysis facilities in 1986 to 1987. MEASUREMENTS: Medical history and service use records, physical examination, and laboratory data. Main outcome measures were receipt of a coronary catheterization or revascularization procedure before (baseline) and after (follow-up) development of ESRD and acquisition of Medicare, adjusted for clinical and socioeconomic variables. RESULTS: At baseline, 9.9% of white patients and 2.8% of black patients had had a cardiac procedure; the odds were almost three times greater in white than in black patients (adjusted odds ratio, 2.92 [95% CI, 2.04 to 4.18]). During follow-up, white patients were only 1.4 times more likely than black patients to have a procedure (adjusted relative risk, 1.41 [CI, 1.13 to 1.77]); rates were 7.8% for white persons and 8.5% for black persons. In patients with Medicare coverage before development of ESRD, the initial three-fold difference in procedure use was eliminated over follow-up (odds ratio, 1.05 [CI, 0.56 to 1.60]). For procedures after hospital admission for myocardial infarction or coronary disease, no difference between ethnic groups was seen during follow-up (relative risk, 1.12 [CI, 0.68 to 1.85]). CONCLUSIONS: Differences between ethnic groups in use of cardiovascular procedures narrowed markedly once a serious illness (ESRD) developed and adequate insurance coverage was ensured; the disparity was eliminated in patients with previous Medicare insurance or a stronger indication for a procedure. These findings suggest that almost equal access to care is attainable by combining insurance with delivery of comprehensive, clinically appropriate care.

Adult↗
PubMed1999

No common major gene for apolipoprotein A-I and HDL3-C levels: evidence from bivariate segregation analysis.

Apolipoprotein A-I (apo A-I) is the most abundant protein in high-density lipoprotein (HDL) particles, and it plays an important role in HDL metabolism. Both apo A-I and HDL cholesterol (HDL-C) levels are inversely associated with risk of cardiovascular disease. Segregation analyses suggest apo A-I levels are under the control of one or more major loci. Since HDL particles are heterogeneous in their composition and size, genetic influence on its subfractions (i.e., HDL2 and HDL3) could vary. A previous report showed evidence of a major locus controlling HDL3-C levels in a subset of the current study population. Because quantitative trait loci involved in complex diseases are likely to have pleiotropic effects on several related traits, it is possible to have a common major gene involved in regulating apo A-I and HDL3-C levels. We performed a bivariate segregation analysis of apo A-I and HDL3-C levels in 1,006 individuals from 137 families ascertained through probands undergoing elective, diagnostic coronary angiography at the Johns Hopkins Hospital. The results showed significant genetic correlation between these two traits, but the hypothesis of a common major gene was rejected. Bivariate segregation analysis favored a model with two genes controlling apo A-I and a third gene independently controlling HDL3-C, and the genetic correlation between these two traits is due to residual additive polygenes. Overall, results from this study suggest that there are distinct genetic mechanisms for apo A-I and HDL3-C levels. Future studies, especially linkage analysis, should consider distinct genetic mechanisms and multiple major gene loci.

Adult↗
PubMed1999

The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive.

BACKGROUND: Rifampin (INN, rifampicin), a CYP34A inducer, results in significant interactions when coadministered with combination oral contraceptives that contain norethindrone (INN, norethisterone) and ethinyl estradiol (INN, ethinylestradiol). Little is known about the effects of rifabutin, a related rifamycin. OBJECTIVES AND METHODS: The relative effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone were evaluated in a prospective, randomized, double-blinded crossover study in 12 premenopausal women who were on a stable oral contraceptive regimen that contained 35 microg ethinyl estradiol/1 mg norethindrone. Subjects were randomized to receive 14 days of rifampin or rifabutin from days 7 through 21 of their menstrual cycle. After a 1-month washout period (only the oral contraceptives were taken), subjects were crossed over to the other rifamycin. RESULTS: Rifampin significantly decreased the mean area under the plasma concentration-time curve from time 0 to 24 hours [AUC(0-24)] of ethinyl estradiol and the mean AUC(0-24) of norethindrone. Rifabutin significantly decreased the mean AUC(0-24) of ethinyl estradiol and the mean AUC(0-24) of norethindrone. The effect of rifampin was significantly greater than rifabutin on each AUC(0-24). Despite these changes, subjects did not ovulate (as determined by progesterone concentrations) during the cycle in which either rifamycin was administered. Levels of mean follicle-stimulating hormone increased 69% after rifampin. CONCLUSION: In this study, rifampin (600 mg daily) was a more significant inducer of ethinyl estradiol and norethindrone clearance than rifabutin (300 mg daily), but neither agent reversed the suppression of ovulation caused by oral contraceptives. The carefully monitored oral contraceptive administration and the limited exposure to rifamycins may restrict the application of this study to clinical situations.

Adult↗