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Mark J Sarnak

Publications and source records attributed to Mark J Sarnak.

51 records · Page 3Linked to original sources

Impact of chronic kidney disease and anemia on hospitalization expense in patients with left ventricular dysfunction.

To estimate the independent effects of kidney disease, anemia, and the treatment effects of angiotensin-converting enzyme (ACE) inhibitors on hospitalization cost in patients with heart failure, we used data from the prevention and treatment trials of the Studies of Left Ventricular Dysfunction trial and retrospectively estimated the relative effects of decreased kidney function, as measured by estimated glomerular filtration rate (GFR) at enrollment, and anemia, as measured by hematocrit levels at enrollment, on hospital utilization and expense. Independent of the effects of age, gender, New York Heart Association (NYHA) class, ejection fraction, and the presence of diabetes mellitus, GFR was significantly related to hospitalization expense (percent change in hospitalization expense -16.8%, 95% confidence interval [CI] -11.9% to -21.5%) for GFR >/=90 ml/min/1.73 m(2) compared with GFR <60 ml/min/1.73 m(2)). Similarly, hematocrit levels were significantly related to hospitalization expense (percent change in hospitalization expense -19.9%, 95% CI -10.2% to -28.6%) for hematocrit >/=36% compared with hematocrit <33%). The beneficial effect of the ACE inhibitor enalapril was significantly related to hospitalization expense independent of the effects of GFR and hematocrit (percent change in hospitalization expense -6.8%, 95% CI -3.6% to -9.9% for treatment vs the placebo group), and the beneficial effect was preserved when independently estimated for subgroups with decreased kidney function. Adjusted mean expense per patient per month (PPPM) in the enalapril group was $708 versus $792 in the placebo group. Comparing survivors, enalapril generated annual cost savings greater than the average wholesale price of the drug at Studies of Left Ventricular Dysfunction mean dosage levels. Adjusted expected hospitalization expense varied from $636 PPPM for patients in the lowest hematocrit-GFR risk class (hematocrit >/=36%, GFR >/=90 ml/min/1.73 m(2)) to $1,127 PPPM for those in the highest risk class (hematocrit <33%, GFR <60 ml/min/1.73 m(2)). For patients who survived with reduced kidney function and anemia, ACE inhibitor therapy with enalapril reduced hospitalization expense more than the additional expense of the drug therapy. Thus, kidney disease and anemia are independent risk factors for hospitalization cost in patients with heart failure, and the beneficial effect of ACE inhibitors on hospitalization expense appears to be preserved within kidney disease and anemia subgroups.

Aged↗

Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community.

OBJECTIVES: The goal of this study was to determine whether the level of kidney function is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) outcomes in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of subjects aged 45 to 64 years. BACKGROUND: The level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD, but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community. METHODS: Cox proportional-hazards regression was used to evaluate the association of glomerular filtration rate (GFR) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects. We searched for nonlinear relationships between GFR and ASCVD. RESULTS: During a mean follow-up time of 6.2 years, 965 (6.3%) of subjects had ASCVD events. Subjects with GFR of 15 to 59 ml/min/1.73 m(2) (n = 444, hazard ratio 1.38 [1.02, 1.87]) and 60 to 89 ml/min/1.73 m(2) (n = 7,665, hazard ratio 1.16 [1.00, 1.34]) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m(2). Each 10 ml/min/1.73 m(2) lower GFR was associated with an adjusted hazard ratio of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), and 1.06 (0.99, 1.13) for ASCVD, de novo ASCVD, and recurrent ASCVD, respectively. A nonlinear model did not fit the data better than a linear model. CONCLUSIONS: The level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study.

Arteriosclerosis↗

Cardiovascular complications in chronic kidney disease.

The risk for cardiovascular disease (CVD) morbidity and mortality remains alarmingly high in all stages of chronic kidney disease (CKD). CVD often begins before end-stage renal disease (ESRD), and patients with reduced kidney function are more likely to die of CVD than to develop ESRD. Three pathological forms of CVD should be considered in patients with CKD: alterations in cardiac geometry, including left ventricular hypertrophy, atherosclerosis, and arteriosclerosis. All are highly prevalent in patients with CKD. Although patients with CKD share many of the same risk factors for CVD as the general population, there are a number of uremia-related risk factors, such as anemia and alterations in calcium/phosphorus metabolism, that also play a role in promoting CVD. Treatment of both traditional and uremia-related risk factors should be initiated in the earlier stages of CKD. Additional clinical trials with a goal to reduce CVD are urgently needed in CKD.

Adult↗

Relationship between C-reactive protein, albumin, and cardiovascular disease in patients with chronic kidney disease.

BACKGROUND: C-Reactive protein (CRP) level is elevated in kidney failure and may be related to malnutrition and cardiovascular disease (CVD). Data are limited regarding relationships between CRP levels and glomerular filtration rate (GFR), nutritional indices, and CVD in patients with earlier stages of kidney disease. METHODS: CRP was assayed from samples from the Modification of Diet in Renal Disease (MDRD) Study (n = 801). CRP distributions were compared between the MDRD Study and National Health and Nutrition Examination Survey (NHANES; 1999 to 2000). Associations between CRP level and GFR, nutritional indices, serum albumin levels, and CVD risk factors were examined in the MDRD Study. RESULTS: Geometric means of CRP, adjusted for age and sex, were similar in NHANES (0.23 mg/dL) and the MDRD Study (0.22 mg/dL). In the MDRD Study, CRP level was related directly to measures of body fat and CVD risk factors, inversely with serum albumin level and energy intake, and unrelated to GFR. In multivariable analysis adjusting for other determinants of serum albumin level, high CRP level (>0.6 mg/dL) was associated with a 0.07-g/dL (0.7-g/L; 95% confidence interval [CI], 0.03 to 0.12) lower mean serum albumin level. After adjusting for traditional CVD risk factors, the odds of CVD were 1.73 (95% CI, 1.07 to 2.78) times greater in subjects with a high CRP level. CONCLUSION: GFR level does not appear to influence CRP level in the earlier stages of chronic kidney disease. CRP levels are independently associated with serum albumin level and CVD prevalence. Inflammation may be involved in the pathophysiological state of malnutrition and CVD in the earlier stages of predominantly nondiabetic kidney disease.

Adolescent↗

Level of kidney function as a risk factor for cardiovascular outcomes in the elderly.

BACKGROUND: There is a high prevalence of both reduced kidney function as well as cardiovascular disease (CVD) in the elderly. We evaluated whether the level of kidney function is an independent risk factor for CVD outcomes in the Cardiovascular Health Study (CHS), a cohort of subjects whose age at baseline was 65 years old or older. METHODS: Cox proportional-hazards regression was used to evaluate the association of predicted glomerular filtration rate (GFR) with CVD after adjustment for the major CVD risk factors. We searched for nonlinear relationships between GFR and CVD, as well as interactions between level of kidney function and major CVD risk factors on CVD. RESULTS: A total of 4893 subjects with predicted GFR of 15 to 130 mL/min/1.73 m2 were included in the analysis. Fifty-six percent were female and the mean age was 73.4 years. Of the subjects, 549 (11.2%) died and 1229 (25.1%) experienced CVD events in 5.05 years of follow-up. Each 10 mL/min/1.73 m2 lower GFR was associated with an adjusted hazard ratio for CVD, de novo CVD, recurrent CVD and all-cause mortality of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), 1.04 (0.99, 1.09), and 1.06 (1.00, 1.12), respectively. There was no significant interaction between level of GFR and other traditional CVD risk factors on CVD outcomes. A linear model best described the relationship between GFR and CVD. CONCLUSION: The level of GFR is an independent risk factor for CVD, de novo CVD, and all-cause mortality in the elderly.

Aged↗

Anemia as a risk factor for cardiovascular disease.

In the present review we examine the physiologic response to chronic anemia and describe potential adverse effects of anemia on myocardial and large arterial remodeling. We present observational data demonstrating that anemia is a risk factor for cardiovascular disease (CVD) outcomes in patients with chronic kidney disease and patients with heart failure. We also present data that have evaluated the relationship of level of hematocrit to CVD outcomes in patients with ischemic heart disease and in patients in the general population. The results from the latter studies have been inconclusive and have been limited by lack of knowledge of the cause of anemia. This is potentially important because iron deficiency anemia may, in fact, improve endothelial function. We conclude that additional randomized controlled trials of treatment of anemia are needed in chronic kidney disease and patients with heart failure; however, further exploration of the cause of anemia and the effect of different types of anemia on various CVD outcomes are needed in patients with ischemic heart disease and patients in the general population.

Anemia↗

Anemia as a risk factor for cardiovascular disease in The Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVES: We investigated whether the presence of anemia is a risk factor for cardiovascular disease (CVD) outcomes in the general population. BACKGROUND: Chronic anemia is a risk factor for CVD outcomes in patients with kidney disease and in patients with heart failure, but has not been evaluated as a risk factor in the general population. METHODS: The Atherosclerosis Risk in Communities (ARIC) study was used to evaluate the relationship of anemia, defined by hemoglobin <13 g/dl in men and <12 g/dl in women, to CVD. Cox proportional hazards regression was used to adjust the relationship between anemia and CVD outcomes for other covariates in the entire study cohort, as well as in subgroups of men, women, African Americans and whites. RESULTS: A total of 14,410 subjects (6,267 men and 8,143 women) without CVD at baseline had hemoglobin levels measured. Three hundred men (4.8%) and 1,058 women (13.0%) were anemic. During an average follow-up of 6.1 years there was a total of 549 (3.8%) CVD events. The presence of anemia was independently associated with an increased risk of CVD (hazard ratio [95% confidence interval] of 1.41 [1.01, 1.95]) in the entire study cohort. In subgroup analyses the hazard ratios were in the same direction, although not statistically significant in all cases. CONCLUSIONS: Anemia is an independent risk factor for CVD outcomes in the ARIC cohort, a community cohort of subjects between the ages of 45 and 64 years.

Anemia↗

Serum C-reactive protein and leptin as predictors of kidney disease progression in the Modification of Diet in Renal Disease Study.

BACKGROUND: In vitro and in vivo data suggest that markers of inflammation and nutritional status may be risk factors for the progression of chronic kidney disease. METHODS: We investigated whether higher levels of C-reactive protein (CRP) and leptin were risk factors for progression of chronic kidney disease in the Modification of Diet in Renal Disease (MDRD) Study. Frozen samples were assayed for high sensitivity C-reactive protein (CRP) or leptin in 804 patients. CRP and leptin were then evaluated as risk factors for glomerular filtration rate (GFR) decline using univariate and multivariable analyses. RESULTS: At baseline, the mean (median) CRP in Study A (GFR between 25 and 55 mL/min/1.73 m2) and Study B (GFR between 13 and 24 mL/min/1.73 m2) were 0.48 (0.25) and 0.46 (0.20) mg/dL, respectively, while the mean (median) leptin in Study A and Study B were 15.2 (9.80) and 15.1 (7.80) ng/mL, respectively. Mean follow-up time was 2.2 years. The mean GFR decline was -4.33 and -3.65 mL/min/year in Study A and B, respectively. There was no significant association between the rate of GFR decline with the level of CRP or leptin in multivariable analysis in Study A [0.08 (-0.14, 0.30) mL/min/year slower GFR decline per twofold increase in CRP level; and 0.14 (-0.13, 0.40) mL/min/year slower GFR decline per twofold increase in leptin level], or in multivariable analysis in Study B [-0.05 (-0.28, 0.18) mL/min/year faster GFR decline per twofold increase in CRP level; and -0.12 (-0.42, 0.19) mL/min/year faster GFR decline per twofold increase in leptin level]. CONCLUSIONS: Higher serum levels of CRP and leptin are not independent risk factors for progression of non-diabetic kidney disease.

Adolescent↗

Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression.

BACKGROUND: Pathological similarities between atherosclerosis and glomerulosclerosis suggest that risk factors for the two processes may be similar. Elevated total homocysteine (tHcy) levels and low B vitamin levels are risk factors for atherosclerosis, but have not been evaluated sufficiently as risk factors for the progression of kidney disease. METHODS: Frozen samples from the Modification of Diet in Renal Disease Study were assayed for serum tHcy, cysteine, pyridoxal 5-phosphate (PLP), folate, and vitamin B12 levels in 804 participants. These factors were evaluated in both continuous and categorical analyses as risk factors for glomerular filtration rate (GFR) decline by using univariate and multivariable analyses. RESULTS: At baseline, mean tHcy levels in study A (GFR, 25 to 55 mL/min/1.73 m2) and study B (GFR, 13 to 24 mL/min/1.73 m2) were 16.9 micromol/L (median, 15.6 micromol/L) and 23.0 micromol/L (median, 20.5 micromol/L), respectively. Mean follow-up was 2.2 years. Mean GFR declines were -4.35 and -3.65 mL/min/y in studies A and B, respectively. There was no significant association between change in GFR with baseline level of tHcy in univariate (-0.26 mL/min/y per 1-SD unit increase in tHcy level; 95% confidence interval [CI], -0.67 to 0.15) or multivariable (-0.18 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.53 to 0.17) analysis in study A or univariate (0.07 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.36 to 0.51) or multivariable (0.24 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.16 to 0.64) analysis in study B. Similarly, higher cysteine levels and lower B vitamin levels were not associated with faster rates of GFR decline in multivariable analysis in either study. CONCLUSION: Higher tHcy or cysteine levels and lower folate, PLP, and vitamin B12 levels are not independent risk factors for progression of nondiabetic kidney disease.

Adolescent↗

Traditional cardiac risk factors in individuals with chronic kidney disease.

Individuals with chronic kidney disease (CKD) are at increased risk for the development and progression of cardiovascular disease (CVD). The increased risk is due to a higher prevalence of both traditional risk factors as well as nontraditional risk factors. In this review we focus on individuals at all stages of CKD and discuss modifiable traditional risk factors, namely hypertension, dyslipidemia, diabetes mellitus and poor glycemic control, smoking, and physical inactivity. The prevalence of each risk factor and its relationship with CVD is described. Treatment recommendations are provided using evidence available from populations with CKD or evidence extrapolated from the general population when there are insufficient data on individuals with CKD.

Cardiovascular Diseases↗

Management of intradialytic hypertension: the ongoing challenge.

There is no widely accepted definition of intradialytic hypertension. Arbitrary clinical definitions have included an increase in blood pressure during or immediately after hemodialysis, a rise in blood pressure during the second or third hour of dialysis, and an increase in blood pressure that is resistant to ultrafiltration. To date, no studies have evaluated the prevalence and prognostic importance of intradialytic hypertension. The pathogenesis of intradialytic hypertension is complex and is due in part to extracellular fluid volume expansion, increased cardiac output, activation of the renin-angiotensin system and the sympathetic nervous system, increased circulating vasoactive substances resulting in peripheral vasoconstriction, erythropoietin use, and fluctuations in electrolytes and removal of antihypertensive medications during the dialysis procedure. Management strategies of intradialytic hypertension are based on expert opinion using the pathophysiologic principles described above. We conclude that additional epidemiologic, basic science, and interventional studies are needed to further elucidate the prevalence, prognostic importance, pathophysiology, and potential treatment of intradialytic hypertension.

Arginine↗