Low birth weight is associated with chronic kidney disease only in men.

The association of low birth weight and chronic kidney disease was examined in a screened volunteer population by the National Kidney Foundation's Kidney Early Evaluation Program. This is a free, community-based health program enrolling individuals aged 18 years or older with diabetes, hypertension, or a family history of kidney disease, diabetes, or hypertension. Self-reported birth weight was categorized and chronic kidney disease defined as an estimated glomerular filtration rate less than 60 ml per min per 1.73 m(2) or a urine albumin/creatinine ratio >or=30 mg/g. Among 12 364 participants, 15% reported a birth weight less than 2500 g. In men, significant corresponding odds ratios were found after adjustment for demographic characteristics and health conditions to this low birth weight and chronic kidney disease, but there was no association among women. There was no significant interaction between birth weight and race for either gender. Efforts to clinically understand the etiology of this association and potential means of prevention are essential to improving public health.

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.

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.

The coming epidemic: hypertension in rural Kyrgyzstan, Central Asia.

Eastern Europe is experiencing an epidemic of cardiovascular disease far outpacing rates in Western Europe. This epidemic was heralded by a precipitous rise in hypertension prevalence. The former Soviet states of Central Asia may be facing a similar epidemic. In order to access this threat, we performed a retrospective analysis of data generated during humanitarian medical visits to two villages in Kyrgyzstan, Central Asia. The age-adjusted prevalence of hypertension was 39%. Hypertension was much more common among men than women (46 vs 33%, respectively). In addition, the rise in blood pressure with age was striking, surpassing the experience in Western countries. This epidemic of hypertension may herald a coming epidemic of cardiovascular disease in Central Asia.

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.

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.

Recreational drug use: a neglected risk factor for end-stage renal disease.

Case series have suggested that heroin and cocaine users are at increased risk for renal failure, but the contribution of heroin and other addictive drugs to the incidence of end-stage renal disease (ESRD) in the general population remains unknown. To clarify this issue, we conducted a case-control study in the general population to examine associations between drug use and treated ESRD. Cases were 716 patients who started therapy for ESRD in 1991, identified through a regional registry. Controls were 361 persons of similar age (20 to 65 years) selected by random digit dialing. Main risk factors examined were the lifetime use of heroin, cocaine, and other addictive drugs, assessed by telephone interview. After adjustment for age, sex, race, socioeconomic status, and history of hypertension and diabetes, persons who had ever used heroin or other opiates (any amount) were at increased risk for ESRD (adjusted odds ratio, 19.1; 95% confidence interval, 1.7 to 208.7). After adjustment for the same sociodemographic and medical history variables, the use of cocaine or crack and psychedelic drugs was also associated with ESRD, but these associations could not be separated from the effects of heroin use.

Alcohol: role in the development of hypertension and end-stage renal disease.

Alcohol is a common risk factor in the general population for a variety of health outcomes. In the present review, we discuss the recent literature on alcohol, hypertension, and renal disease. The regular consumption of more than two drinks per day is associated with both hypertension and renal disease. The mechanisms by which consumption of alcohol leads to hypertension and perhaps renal disease are unknown.

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.

Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials.

Coffee drinking has been associated with increased serum cholesterol levels in some, but not all, studies. A Medline search of the English-language literature published prior to December 1998, a bibliography review, and consultations with experts were performed to identify 14 published trials of coffee consumption. Information was abstracted independently by two reviewers using a standardized protocol. With a random-effects model, treatment effects were estimated by pooling results from individual trials after weighting the results by the inverse of total variance. A dose-response relation between coffee consumption and both total cholesterol and LDL cholesterol was identified (p < 0.01). Increases in serum lipids were greater in studies of patients with hyperlipidemia and in trials of caffeinated or boiled coffee. Trials using filtered coffee demonstrated very little increase in serum cholesterol. Consumption of unfiltered, but not filtered, coffee increases serum levels of total and LDL cholesterol.

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,

Physician, heal Thyself? Regular source of care and use of preventive health services among physicians.

BACKGROUND: Little is known about the regular source of care (RSOC) among physicians, a group whose self-care may reflect the attitudes and recommendations they convey to their patients. METHODS: We performed a cohort study of physicians who graduated from the Johns Hopkins School of Medicine from 1948 through 1964 to identify predictors of not having an RSOC, and to determine whether not having an RSOC was associated with subsequent receipt of preventive services. The RSOC was assessed in a 1991 survey; use of cancer screening tests and the influenza vaccine was assessed in 1997. RESULTS: The response rate in 1991 was 77% (915 respondents); 35% (312) had no RSOC. Internists (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.58-6.74), surgeons (OR, 2.42; 95% CI, 1.17-5.02), and pathologists (OR, 5.46; 95% CI, 2.09-14.29) were significantly more likely to not have an RSOC than pediatricians. Not having an RSOC was inversely related to the belief that health is determined by health professionals (OR, 0.45; 95% CI, 0.29-0.68) and directly related to the belief that chance (OR, 1.90; 95% CI, 1.28-2.82) determines health. Not having an RSOC in 1991 predicted not being screened for breast, colon, and prostate cancer, as well as not receiving an influenza vaccine at 6 years of follow-up. CONCLUSIONS: A large percentage of physicians in our sample had no RSOC, and this was associated with both medical specialty and beliefs about control of health outcomes. Not having an RSOC was significantly associated with failure to use preventive services several years later. Arch Intern Med. 2000;160:3209-3214.

Joint injury in young adults and risk for subsequent knee and hip osteoarthritis.

BACKGROUND: Knee and hip injuries have been linked with osteoarthritis in cross-sectional and case-control studies, but few prospective studies have examined the relation between injuries in young adults and risk for later osteoarthritis. OBJECTIVE: To prospectively examine the relation between joint injury and incident knee and hip osteoarthritis. DESIGN: Prospective cohort study. SETTING: Johns Hopkins Precursors Study. PARTICIPANTS: 1321 former medical students. MEASUREMENTS: Injury status at cohort entry was recorded when the mean age of participants was 22 years. Injury during follow-up and incident osteoarthritis were determined by using self-administered questionnaires. Osteoarthritis was confirmed by symptoms and radiographic findings. RESULTS: Over a median follow-up of 36 years, 141 participants reported joint injuries (knee alone [n = 111], hip alone [n = 16], or knee and hip [n = 14]) and 96 developed osteoarthritis (knee alone [n = 64], hip alone [n = 27], or knee and hip [n = 5]). The cumulative incidence of knee osteoarthritis by 65 years of age was 13.9% in participants who had a knee injury during adolescence and young adulthood and 6.0% in those who did not (P = 0.0045) (relative risk, 2.95 [95% CI, 1.35 to 6.45]). Joint injury at cohort entry or during follow-up substantially increased the risk for subsequent osteoarthritis at that site (relative risk, 5.17 [CI, 3.07 to 8.71] and 3.50 [CI, 0.84 to 14.69] for knee and hip, respectively). Results were similar for persons with osteoarthritis confirmed by radiographs and symptoms. CONCLUSIONS: Young adults with knee injuries are at considerably increased risk for osteoarthritis later in life and should be targeted in the primary prevention of osteoarthritis.

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

Feasibility of using recipients of health promotional newsletters for post-marketing surveillance.

Achieving an adequate sample size is one of the major difficulties in performing post-marketing observational studies of health outcomes in persons taking specific drug preparations. We assessed the feasibility of recruiting participants for such a study of Cardizem CD from approximately 400,000 U.S. recipients of a health promotion newsletter. A three-page questionnaire was sent to a 2.5% random sample (n = 10,000) of recipients, stratified by geographic region. After two mailings, 2779 (28%) returned the questionnaire. Of the 2779 respondents, 2132 (77%) reported having high blood pressure. Eighty-seven percent indicated a willingness to participate in a long-term prospective study. In a multivariate model, calcium channel blocker (CCB) use was associated with a history of coronary heart disease, duration of hypertension medication use greater than 1 year, a rating of good or excellent hypertension care, higher systolic blood pressure, higher education level, family history of cardiovascular disease, and history of smoking. These results indicate that self-reported CCB users may be at greater risk of cardiovascular heart disease and that it is feasible to use health promotion newsletters as a source of participants in prospective studies of cardiovascular disease.

Vitamin C status and mortality in US adults.

BACKGROUND: Low vitamin C status may increase the risk of mortality from cancer and cardiovascular disease. OBJECTIVE: The objective was to test whether an association existed between serum ascorbate concentrations and mortality and whether the association was modified by cigarette smoking status or sex. DESIGN: Serum ascorbate concentrations were measured in adults as part of the second National Health and Nutrition Examination Survey (1976-1980). Vital status was ascertained 12-16 y later. RESULTS: The relative risk (RR) of death, adjusted for potential confounders, was estimated by using Cox proportional hazards models. Men in the lowest (<28.4 micromol/L) compared with the highest (>/=73.8 micromol/L) serum ascorbate quartile had a 57% higher risk of dying from any cause (RR: 1.57; 95% CI: 1.21, 2.03) and a 62% higher risk of dying from cancer (RR: 1.62; 95% CI: 1.01, 2.59). In contrast, there was no increased risk among men in the middle 2 quartiles for these outcomes and no increased risk of cardiovascular disease mortality in any quartile. There was no association between serum ascorbate quartile and mortality among women. These findings were consistent when analyses were limited to nonsmokers or further to adults who never smoked, suggesting that the observed relations were not due to cigarette smoking. CONCLUSIONS: These data suggest that men with low serum ascorbate concentrations may have an increased risk of mortality, probably because of an increased risk of dying from cancer. In contrast, serum ascorbate concentrations were not related to mortality among women.

Long-term effects of weight loss and dietary sodium reduction on incidence of hypertension.

To examine the long-term effects of weight loss and dietary sodium reduction on the incidence of hypertension, we studied 181 men and women who participated in the Trials of Hypertension Prevention, phase 1, in Baltimore, Md. At baseline (1987 to 1988), subjects were 30 to 54 years old and had a diastolic blood pressure (BP) of 80 to 89 mm Hg and systolic BP <160 mm Hg. They were randomly assigned to one of two 18-month lifestyle modification interventions aimed at either weight loss or dietary sodium reduction or to a usual care control group. At the posttrial follow-up (1994 to 1995), BP was measured by blinded observers who used a random-zero sphygmomanometer. Incident hypertension was defined as systolic BP > or =160 mm Hg and/or diastolic BP > or =90 mm Hg and/or treatment with antihypertensive medication during follow-up. Body weight and urinary sodium were not significantly different among the groups at the posttrial follow-up. After 7 years of follow-up, the incidence of hypertension was 18.9% in the weight loss group and 40.5% in its control group and 22.4% in the sodium reduction group and 32.9% in its control group. In logistic regression analysis adjusted for baseline age, gender, race, physical activity, alcohol consumption, education, body weight, systolic BP, and urinary sodium excretion, the odds of hypertension was reduced by 77% (odds ratio 0.23; 95% confidence interval 0.07 to 0.76; P=0.02) in the weight loss group and by 35% (odds ratio 0.65; 95% confidence interval 0.25 to 1.69; P=0.37) in the sodium reduction group compared with their control groups. These results indicate that lifestyle modification such as weight loss may be effective in long-term primary prevention of hypertension.

Risk of end-stage renal disease associated with alcohol consumption.

Alcohol consumption has been linked to kidney disorders in selected patient groups, but whether it contributes to the burden of end-stage renal disease (ESRD) in the general population is unknown. The authors conducted a population-based case-control study to assess the relation between alcohol consumption and risk of ESRD. The study took place in Maryland, Virginia, West Virginia, and Washington, DC, in 1991. Participants were 716 patients who had started treatment for ESRD and 361 control subjects of similar age (20-64 years) selected by random digit dialing. The main risk factor of interest was self-reported consumption of alcoholic beverages (frequency of drinking days and number of drinks consumed per drinking day). In univariate analysis, consumption of alcohol exhibited a J-shaped association with risk of ESRD. The J shape disappeared after exclusion of persons who had ever consumed home-distilled whiskey ("moonshine") and adjustment for age, race, sex, income, history of hypertension, history of diabetes mellitus, use of acetaminophen, use of opiates, and cigarette smoking; however, the odds ratio for ESRD remained significantly increased (odds ratio = 4.0; 95% confidence interval: 1.2, 13.0) among persons who consumed an average of >2 alcoholic drinks per day. The corresponding population attributable risk was 9 percent. Thus, consumption of more than two alcoholic drinks per day, on average, was associated with an increased risk of kidney failure in the general population. A lower intake of alcohol did not appear to be harmful. Because these results are based on self-reports in a case-control study, they should be seen as preliminary.

The renin-angiotensin system and blood pressure: differences between blacks and whites.

Although blacks have lower plasma renin activity compared to whites, the corresponding differences in serum angiotensin converting enzyme (ACE) levels have not been well studied. Furthermore, few studies have examined the relationship of renin activity and ACE levels to blood pressure (BP) in blacks. We addressed these questions in a cross-sectional study conducted in 110 blacks and 183 whites who were not on antihypertensive medications. Three BP readings were obtained during a clinic visit. Plasma renin activity was assayed by radioimmunoassay and serum ACE levels were measured by spectrophotometry. Mean systolic and diastolic BP were 122.6 and 77.9 mm Hg in the blacks, and 123.4 and 77.9 mm Hg in the whites, respectively. Plasma renin activity was significantly lower in the blacks compared to the whites (0.92 v 1.26 ng/mL/h, respectively, P < .05), but ACE levels were similar in both groups (28.8 v 29.6 U/L, respectively). Renin activity was significantly and inversely associated with systolic and diastolic BP in both the blacks and the whites. ACE levels, however, were inversely associated with BP in the blacks but positively associated with BP in the whites (P = .02 for interaction on diastolic BP), even after adjustment for age, gender, body mass index (BMI), alcohol consumption, and heart rate. The corresponding interaction between ACE level and race on systolic BP was of borderline significance (P = .06). These results suggest that levels of ACE are similar in blacks and whites but their association with BP is possibly reflecting underlying ethnic differences in regulation of BP.