M J Klag

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (81)812.78 Total impact

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    ABSTRACT: 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. 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). 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. 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%. 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.
    Journal of Medical Genetics 12/2006; 43(12):917-23. DOI:10.1136/jmg.2006.042119 · 5.64 Impact Factor
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    ABSTRACT: 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.
    Kidney International 07/2006; 70(2):351-7. DOI:10.1038/sj.ki.5001542 · 8.52 Impact Factor
  • Seminars in Dialysis 05/2005; 18(3). DOI:10.1111/j.1525-139X.2005.18324.x · 2.07 Impact Factor
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    ABSTRACT: 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.
    Journal of Human Hypertension 03/2005; 19(2):145-8. DOI:10.1038/sj.jhh.1001791 · 2.69 Impact Factor
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    ABSTRACT: BACKGROUND: Bisphosphonates are potent therapies for osteoporosis, but some patients cannot tolerate oral forms. Our study sought to examine the effectiveness and safety of intravenous pamidronate as an alternate osteoporotic therapy in these patients. METHODS: We conducted a retrospective study of 26 patients treated with intermittent, intravenous pamidronate (30 mg every 3 months) and 52 matched controls treated with standard therapy, all with osteoporosis. Primary outcome was response to therapy, defined as either stabilization or increase in bone mineral density. Secondary outcomes were patient safety and tolerability. RESULTS: At an average of 16.1 months of follow up, 64% of pamidronate-treated patients responded to therapy at the lumbar spine, 65% at the femoral neck, and 63% at the trochanter. These response rates were not significantly different than those of the standard care group in which 69% were receiving oral bisphosphonates. Adverse events were uncommon and included mild, diffuse myalgi
    JCR Journal of Clinical Rheumatology 02/2005; 11(1):2-7. DOI:10.1097/01.rhu.0000152141.47663.e4 · 1.25 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Clinical nephrology 06/2004; 61(5):299-307. DOI:10.5414/CNP61299 · 1.23 Impact Factor
  • M.J. Klag, N.H. Wang, L.A. Meoni
    ACC Current Journal Review 09/2002; 11(5):29. DOI:10.1016/S1062-1458(02)00779-1
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    ABSTRACT: 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. 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. 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. Elevated serum creatinine level, an indicator of chronic renal disease, is common and strongly related to inadequate treatment of high blood pressure.
    Archives of Internal Medicine 05/2001; 161(9):1207-16. · 13.25 Impact Factor
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    ABSTRACT: 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.
    American Journal of Epidemiology 02/2001; 153(4):353-62. · 4.98 Impact Factor
  • Hipertensión y Riesgo Vascular 01/2001; 18(1):53–54. DOI:10.1016/S1889-1837(01)71110-5
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    C P Gross, LA Mead, D E Ford, M J Klag
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    ABSTRACT: 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. 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. 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. 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.
    Archives of Internal Medicine 12/2000; 160(21):3209-14. DOI:10.1001/archinte.160.21.3209 · 13.25 Impact Factor
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    ABSTRACT: 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. To prospectively examine the relation between joint injury and incident knee and hip osteoarthritis. Prospective cohort study. Johns Hopkins Precursors Study. 1321 former medical students. 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. 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. 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.
    Annals of internal medicine 10/2000; 133(5):321-8. · 16.10 Impact Factor
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    ABSTRACT: Low vitamin C status may increase the risk of mortality from cancer and cardiovascular disease. 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. 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. 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. 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.
    American Journal of Clinical Nutrition 07/2000; 72(1):139-45. · 6.92 Impact Factor
  • F D Fuchs, M J Klag, P K Whelton
    Journal of Clinical Epidemiology 05/2000; 53(4):335-42. DOI:10.1016/S0895-4356(99)00185-7 · 5.48 Impact Factor
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    ABSTRACT: Since 1995, the Medical Evidence Report for end-stage renal disease (Form 2728) has been used nationally to collect information on comorbid conditions. To date, these data have not been validated. A national cross-sectional study of 1005 incident dialysis patients (734 hemodialysis and 271 peritoneal dialysis) enrolled between October 1995 and June 1998 was conducted using clinical data to validate 17 comorbid conditions on Form 2728. Sensitivity and specificity were calculated for each condition. The relationship between patient characteristics and sensitivity was assessed in multivariate analysis. Sensitivity was fairly high (0.67 to 0.83) for HIV disease, diabetes, and hypertension; intermediate (0.40 to 0.52) for peripheral vascular disease, neoplasm, myocardial infarction, cerebrovascular disease, coronary artery disease, cardiac arrest, and congestive heart failure; and poor (<0.36) for dysrhythmia, ambulation status, pericarditis, chronic obstructive pulmonary disease, and smoking. Sensitivity did not change significantly over calendar time. The sensitivity of Form 2728 averaged across all 17 conditions was 0.59 (95% confidence interval, 0.43 to 0.75). The average sensitivity was 0.10 greater in peritoneal dialysis than hemodialysis patients. 0.11 greater in diabetic patients than nondiabetic patients, and 0.04 less with each added comorbid condition. The specificity was very good for hypertension (0.91) and excellent (>0.95) for the other 16 conditions. Comorbid conditions are significantly underreported on Form 2728, but diagnoses are not falsely attributed to patients. Scientific research, quality of care comparisons, and payment policies that use Form 2728 data should take into account these limitations. Considerable effort should be expended to improve Form 2728 coding if it is to provide accurate estimates of total disease burden in end-stage renal disease patients.
    Journal of the American Society of Nephrology 03/2000; 11(3):520-9. · 9.47 Impact Factor
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    ABSTRACT: 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.
    Hypertension 03/2000; 35(2):544-9. DOI:10.1161/01.HYP.35.2.544 · 7.63 Impact Factor
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    ABSTRACT: 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.
    American Journal of Epidemiology 12/1999; 150(12):1275-81. DOI:10.1093/oxfordjournals.aje.a009958 · 4.98 Impact Factor
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    ABSTRACT: 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.
    American Journal of Hypertension 06/1999; 12(6):555-62. DOI:10.1016/S0895-7061(99)00030-8 · 3.40 Impact Factor
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    S H Jee, J He, P K Whelton, I Suh, M J Klag
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    ABSTRACT: We sought to assess the effect of coffee consumption on blood pressure in humans. Our data sources included a MEDLINE search of the literature published before December 1997, bibliography review, and expert consultation. We selected controlled trials in which coffee consumption was the only difference between the intervention and control groups, mean blood pressure change was reported for each group or period, and treatment lasted for >24 hours. Of 36 studies initially identified, 11 (522 participants) met these inclusion criteria. Information on sample size, study design, participant characteristics (gender, race, age, baseline blood pressure, and antihypertensive medications), and treatment results were abstracted by 3 reviewers using a standardized protocol. Treatment effect of coffee consumption on blood pressure was estimated with the use of a random-effects model. In the 11 trials, median duration was 56 days (range, 14 to 79 days), and median dose of coffee was 5 cups/d. Systolic and diastolic blood pressure increased by 2.4 (range, 1.0 to 3.7) mm Hg and 1.2 (range, 0.4 to 2.1) mm Hg, respectively, with coffee treatment compared with control. Multiple linear regression analysis identified an independent, positive relationship between cups of coffee consumed and subsequent change in systolic blood pressure, independent of age of study participants and study design characteristics. The effect of coffee drinking on systolic and diastolic blood pressure was greater in trials with younger participants. Our findings provide support for a relationship between coffee consumption and higher blood pressure. Trials of coffee cessation of longer duration and in persons with hypertension should be performed.
    Hypertension 03/1999; 33(2):647-52. DOI:10.1161/01.HYP.33.2.647 · 7.63 Impact Factor
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    ABSTRACT: Treatment and prevention of cardiovascular disease in the general population has benefited greatly from the identification of cardiovascular disease risk factors. Given the particularly high risk of cardiovascular disease and total mortality among patients with chronic renal insufficiency (CRI) and end-stage renal disease (ESRD), it is important to assess the role of traditional and nontraditional risk factors for cardiovascular disease. This review discusses the foundations of risk factor epidemiology and briefly summarizes the evidence regarding cardiovascular risk factors in renal disease. Diabetes and hypertension have a very high prevalence in patients with CRI. Patients with CRI and ESRD also have a higher frequency of cardiac dysfunction and left ventricular hypertrophy, which further increase the risk of cardiovascular disease. Finally, patients with renal disease have a higher prevalence of less established risk factors, including low HDL, and high triglycerides, lipoprotein(a), and homocysteine, where prospective studies and clinical trials are needed to provide a scientific basis for reduction of cardiovascular risk among patients with renal disease.
    Journal of the American Society of Nephrology 01/1999; 9(12 Suppl):S24-30. · 9.47 Impact Factor

Publication Stats

6k Citations
812.78 Total Impact Points

Institutions

  • 1991–2006
    • Johns Hopkins University
      • • Department of Medicine
      • • Welch Center for Prevention, Epidemiology, and Clinical Research
      Baltimore, Maryland, United States
  • 2000
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 1994–1999
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Epidemiology
      Baltimore, Maryland, United States
  • 1998
    • Centers for Disease Control and Prevention
      • National Center for Health Statistics
      Druid Hills, GA, United States
  • 1989–1998
    • Johns Hopkins Medicine
      • • Department of Medicine
      • • Welch Center for Prevention, Epidemiology and Clinical Research
      • • Department of Health Policy and Management
      Baltimore, MD, United States
  • 1997
    • Tulane University
      • Department of Epidemiology
      New Orleans, LA, United States
  • 1995
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States