Claudine Jurkovitz

Effect of PCI on Quality of Life in Patients with Stable Coronary Disease

BACKGROUND It has not been clearly established whether percutaneous coronary intervention (PCI) can provide an incremental benefit in quality of life over that provided by optimal medical therapy among patients with chronic coronary artery disease. METHODS We randomly assigned 2287 patients with stable coronary disease to PCI plus optimal medical therapy or to optimal medical therapy alone. We assessed angina-specific health status (with the use of the Seattle Angina Questionnaire) and overall physical and mental function (with the use of the RAND 36-item health survey [RAND-36]). RESULTS At baseline, 22% of the patients were free of angina. At 3 months, 53% of the patients in the PCI group and 42% in the medical-therapy group were angina-free (P<0.001). Baseline mean (+/-SD) Seattle Angina Questionnaire scores (which range from 0 to 100, with higher scores indicating better health status) were 66+/-25 for physical limitations, 54+/-32 for angina stability, 69+/-26 for angina frequency, 87+/-16 for treatment satisfaction, and 51+/-25 for quality of life. By 3 months, these scores had increased in the PCI group, as compared with the medical-therapy group, to 76+/-24 versus 72+/-23 for physical limitation (P=0.004), 77+/-28 versus 73+/-27 for angina stability (P=0.002), 85+/-22 versus 80+/-23 for angina frequency (P<0.001), 92+/-12 versus 90+/-14 for treatment satisfaction (P<0.001), and 73+/-22 versus 68+/-23 for quality of life (P<0.001). In general, patients had an incremental benefit from PCI for 6 to 24 months; patients with more severe angina had a greater benefit from PCI. Similar incremental benefits from PCI were seen in some but not all RAND-36 domains. By 36 months, there was no significant difference in health status between the treatment groups. CONCLUSIONS Among patients with stable angina, both those treated with PCI and those treated with optimal medical therapy alone had marked improvements in health status during follow-up. The PCI group had small, but significant, incremental benefits that disappeared by 36 months. (ClinicalTrials.gov number, NCT00007657.)

Anemia and Renal Insufficiency Are Independent Risk Factors for Death among Patients with Congestive Heart Failure Admitted to Community Hospitals: A Population-Based Study

The purpose of this retrospective cohort study was to examine the associations among chronic kidney disease, anemia, and risk of death among patients with heart failure. Retrospective cohort study. Patients with a principal diagnosis of heart failure (ICD9 codes 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, and 428.xx) were included. Chronic kidney disease (CKD) was defined as a serum creatinine >1.4 mg/dl for women and >1.5 mg/dl for men. There were 665 eligible patients in the sample with a mean (SD) age of 75.7 (10.9) yr; 60% were women, 71% were white, and 38% had CKD. On admission, a hematocrit > or =40% was found for 30.3% of the patients; 22.9% had a hematocrit between 36% and 40%, 33.2% between 30% and 35%, and 13.6% had a hematocrit of <30%. The 1-yr death rates among individuals with and without CKD were 44.9% and 31.4%, respectively (relative risk [RR], 1.43; 95% confidence interval [CI], 1.17 to 1.75). The mortality at 1 yr was 31.2% for individuals with a hematocrit > or =40%; 33.8% (RR, 1.08; 95% CI. 0.79 to 1.47) for hematocrit 36 to 39%; 36.7% (RR, 1.17; 95% CI, 0.89 to 1.54) for hematocrit between 30 and 35%; and 50.0% (RR, 1.60; 95% CI, 1.19 to 2.16) for those with a hematocrit <30% (chi(2) for trend was 7.37; P = 0.007). Both hematocrit and serum creatinine were independently associated with increased risk of death during follow-up after controlling for other patient risk factors. In conclusion, CKD and anemia are frequent among older patients with heart failure and are independent predictors of subsequent risk of death.

Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting.

The ubiquitin-proteasome proteolytic system is stimulated in conditions causing muscle atrophy. Signals initiating this response in these conditions are unknown, although glucocorticoids are required but insufficient to stimulate muscle proteolysis in starvation, acidosis, and sepsis. To identify signals that activate this system, we studied acutely diabetic rats that had metabolic acidosis and increased corticosterone production. Protein degradation was increased 52% ( P < 0.05), and mRNA levels encoding ubiquitin-proteasome system components, including the ubiquitin-conjugating enzyme E214k, were higher (transcription of the ubiquitin and proteasome subunit C3 genes in muscle was increased by nuclear run-off assay). In diabetic rats, prevention of acidemia by oral NaHCO3 did not eliminate muscle proteolysis. Adrenalectomy blocked accelerated proteolysis and the rise in pathway mRNAs; both responses were restored by administration of a physiological dose of glucocorticoids to adrenalectomized, diabetic rats. Finally, treating diabetic rats with insulin for ≥24 h reversed muscle proteolysis and returned pathway mRNAs to control levels. Thus acidification is not necessary for these responses, but glucocorticoids and a low insulin level in tandem activate the ubiquitin-proteasome proteolytic system.The ubiquitin-proteasome proteolytic system is stimulated in conditions causing muscle atrophy. Signals initiating this response in these conditions are unknown, although glucocorticoids are required but insufficient to stimulate muscle proteolysis in starvation, acidosis, and sepsis. To identify signals that activate this system, we studied acutely diabetic rats that had metabolic acidosis and increased corticosterone production. Protein degradation was increased 52% (P < 0.05), and mRNA levels encoding ubiquitin-proteasome system components, including the ubiquitin-conjugating enzyme E214k, were higher (transcription of the ubiquitin and proteasome subunit C3 genes in muscle was increased by nuclear run-off assay). In diabetic rats, prevention of acidemia by oral NaHCO3 did not eliminate muscle proteolysis. Adrenalectomy blocked accelerated proteolysis and the rise in pathway mRNAs; both responses were restored by administration of a physiological dose of glucocorticoids to adrenalectomized, diabetic rats. Finally, treating diabetic rats with insulin for >/=24 h reversed muscle proteolysis and returned pathway mRNAs to control levels. Thus acidification is not necessary for these responses, but glucocorticoids and a low insulin level in tandem activate the ubiquitin-proteasome proteolytic system.

Association of High Serum Creatinine and Anemia Increases the Risk of Coronary Events: Results from the Prospective Community-Based Atherosclerosis Risk in Communities (ARIC) Study

Coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with chronic kidney disease or anemia. The purpose of this study was to examine whether the association between renal function and risk of CHD is modified by hemoglobin (Hgb) status. Analyses were based on data from the Atherosclerosis Risk in Communities study, a community-based study of risk factors for CHD in middle-aged people. People with known CHD at baseline were excluded from the analysis. Participants were followed for 9 yr for the occurrence of CHD. Anemia was defined as Hgb <13 g/dl in men and <12 g/dl in women. Cox proportional hazards models were used to assess the relative risk (RR) of CHD occurrence according to Hgb status, after adjusting for other risk factors (demographics, lipids, diabetes, hypertension, smoking, body mass index, and carotid intima-media thickness). A total of 13,329 participants were included. The interaction between Hgb concentration and serum creatinine (Scr) was significant (P = 0.02). Among people with anemia, a Scr >/=1.2 mg/dl in women or >/=1.5 mg/dl in men was associated with a higher risk of CHD (RR, 2.74; 95% confidence interval, 1.42 to 5.28) than those with normal Scr. In contrast, among those without anemia, this association was not noted (RR, 1.20; 95% confidence interval, 0.86 to 1.67). In conclusion, this study indicates that high Scr is associated with almost a threefold risk of CHD among middle-aged people with anemia, whereas no increased risk is found in people with high Scr in the absence of anemia.

Prevalence of CKD and Comorbid Illness in Elderly Patients in the United States: Results From the Kidney Early Evaluation Program (KEEP)

BACKGROUND Elderly individuals with chronic kidney disease (CKD) have high rates of comorbid conditions, including cardiovascular disease and its risk factors, and CKD-related complications. In individuals aged > or = 65 years, we sought to describe the prevalence of CKD determined from laboratory test results in the Kidney Early Evaluation Program (KEEP; n = 27,017) and National Health and Nutrition Examination Survey (NHANES) 1999-2006 (n = 5,538) and the prevalence of diagnosed CKD determined from billing codes in the Medicare 5% sample (n = 1,236,946). In all 3 data sources, we also explored comorbid conditions and CKD-related complications. METHODS CKD was identified as decreased estimated glomerular filtration rate (<60 mL/min/1.73 m(2)) or increased albumin-creatinine ratio in KEEP and NHANES; CKD was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes in Medicare. Investigated comorbid conditions included diabetes, hypertension, high cholesterol level, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and cancer, and CKD-related complications included anemia, hypocalcemia, hyperphosphatemia, and hyperparathyroidism. RESULTS The prevalence of CKD was approximately 44% in both KEEP and NHANES participants, and the prevalence of diagnosed CKD was 7% in Medicare beneficiaries. In all 3 data sets, the prevalence of CKD or diagnosed CKD was higher in participants aged > or = 80 years and those with comorbid conditions. For KEEP and NHANES participants, the prevalence of most comorbid conditions and CKD complications increased with decreasing estimated glomerular filtration rate. For participants with CKD stages 3-5, a total of 29.2% (95% CI, 27.8-30.6) in KEEP and 19.9% (95% CI, 17.0-23.1) in NHANES had anemia, 0.7% (95% CI, 0.4-0.9) and 0.6% (95% CI, 0.3-1.3) had hypocalcemia, 5.4% (95% CI, 4.7-6.1) and 6.4% (95% CI, 5.1-8.0) had hyperphosphatemia, and 52.0% (95% CI, 50.4-53.6) and 30.0% (95% CI, 25.9-34.3) had hyperparathyroidism, respectively. CONCLUSIONS CKD is common in the elderly population and is associated with high frequencies of concomitant comorbid conditions and biochemical abnormalities. Because CKD is not commonly diagnosed, greater emphasis on physician education may be beneficial.

Chronic kidney disease, prevalence of premature cardiovascular disease, and relationship to short-term mortality

BACKGROUND Chronic kidney disease (CKD) is recognized as an independent cardiovascular disease (CVD) risk state, particularly in the elderly, and has been defined by levels of estimated glomerular filtration rate (eGFR) and markers of kidney damage. The relationship between CKD and CVD in younger and middle-aged adults has not been fully explored. METHODS Community volunteers completed surveys regarding past medical events and underwent blood pressure and laboratory testing. Chronic kidney disease was defined as an eGFR <60 mL x min(-1) x 1.73 m(-2) or urine albumin-creatinine ratio (ACR) > or =30 mg/g. Premature CVD was defined as self-reported myocardial infarction or stroke at <55 years of age in men and <65 years of age in women. Mortality was ascertained by linkage to national data systems. RESULTS Of 31 417 participants, the mean age was 45.1 +/- 11.2 years, 75.5% were female, 36.8% African American, and 21.6% had diabetes. A total of 20.6% were found to have CKD, with the ACR and eGFR being the dominant positive screening tests in the younger and older age deciles, respectively. The prevalences of premature myocardial infarction (MI), stroke, or death, and the composite were 5.3%, 4.7%, 0.8%, 9.2%, and 2.5%, 2.2%, 0.2%, 4.2% for those with and without CKD, respectively (P < .0001 for composite). Multivariable analysis found CKD (OR 1.44, 95% CI 1.27-1.63), age (OR 1.05 [per year], 95% CI 1.04-1.06), hypertension (OR 1.61, 95% CI 1.40-1.84), diabetes (OR 2.03, 95% CI 1.79-2.29), smoking (OR 1.91, 95% CI 1.66-2.21), and less than high school education (OR 1.59, 95% CI 1.37-1.85) as the most significantly associated factors for premature CVD or death (all P < .0001). Survival analysis found those with premature MI or stroke and CKD had the poorest short-term survival over the next 3 years after screening. CONCLUSIONS Chronic kidney disease is an independent predictor of MI, stroke, and death among men and women younger than age 55 and 65 years, respectively. These data suggest the biologic changes that occur with kidney failure promote CVD at an accelerated rate that cannot be fully explained by conventional risk factors or older age. Screening for CKD by using both the ACR and eGFR can identify younger and middle-aged individuals at high risk for premature CVD and near-term death.

CKD and cardiovascular disease in screened high-risk volunteer and general populations: the Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999-2004.

BACKGROUND Chronic kidney disease (CKD) is recognized as an independent cardiovascular disease risk state. The relationship between CKD and cardiovascular disease in volunteer and general populations has not been explored. METHODS The National Kidney Foundation Kidney Early Evaluation Program (KEEP) is a community-based health-screening program to raise kidney disease awareness and detect CKD for early disease intervention in individuals 18 years or older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension. KEEP volunteers completed surveys and underwent blood pressure and laboratory testing. Estimated glomerular filtration rate (eGFR) was computed, and urine albumin-creatinine ratio (ACR) was measured. In KEEP, CKD was defined as eGFR less than 60 mL/min/1.73 m(2) or ACR of 30 mg/g or greater. Cardiovascular disease was defined as self-reported myocardial infarction or stroke. Data were compared with National Health and Nutrition Examination Survey (NHANES) 1999-2004 data for prevalence of cardiovascular disease risk factors and cardiovascular outcomes. RESULTS Of 69,244 KEEP participants, mean age was 53.4 +/- 15.7 years, 68.3% were women, 33.0% were African American, and 27.6% had diabetes. Of 17,061 NHANES participants, mean age was 45.1 +/- 0.27 years, 52% were women, 11.2% were African American, and 6.7% had diabetes. In KEEP, 26.8% had CKD, and in NHANES, 15.3%. ACR was the dominant positive screening test for younger age groups, and eGFR, for older age groups, for both populations. Prevalences of myocardial infarction or stroke were 16.5% in KEEP and 15.1% in NHANES (P < 0.001) and 7.8% in KEEP and 3.7% in NHANES (P < 0.001) for individuals with and without CKD, respectively. In adjusted analysis of both KEEP and NHANES data, CKD was associated with a significantly increased risk of prevalent myocardial infarction or stroke (odds ratio, 1.34; 95% confidence interval, 1.25 to 1.43; odds ratio, 1.37; 95% confidence interval, 1.10 to 1.70, respectively). In KEEP, short-term mortality was greater in individuals with CKD (1.52 versus 0.33 events/1,000 patient-years). CONCLUSIONS CKD is independently associated with myocardial infarction or stroke in participants in a voluntary screening program and a randomly selected survey population. Heightened concerns regarding risks in volunteers yielded greater cardiovascular disease prevalence in KEEP, which was associated with increased short-term mortality.

Cost-Effectiveness of Percutaneous Coronary Intervention in Optimally Treated Stable Coronary Patients

Background—The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluations) trial compared the effect of percutaneous coronary intervention (PCI) plus optimal medical therapy with optimal medical therapy alone on cardiovascular events in 2287 patients with stable coronary disease. After 4.6 years, there was no difference in the primary end point of death or myocardial infarction, although PCI improved quality of life. The present study evaluated the relative cost and cost-effectiveness of PCI in the COURAGE trial. Methods and Results—Resource use was assessed by diagnosis-related group for hospitalizations and by current procedural terminology code for outpatient visits and tests and then converted to costs by use of 2004 Medicare payments. Medication costs were assessed with the Red Book average wholesale price. Life expectancy beyond the trial was estimated from Framingham survival data. Utilities were assessed by the standard gamble method. The incremental cost-effectiveness ratio was expressed as cost per life-year and cost per quality-adjusted life-year gained. The added cost of PCI was approximately

Population-Based Screening for Family History of End-Stage Renal Disease among Incident Dialysis Patients

10 000, without significant gain in life-years or quality-adjusted life-years. The incremental cost-effectiveness ratio varied from just over

Intravascular Radiation Therapy after Balloon Angioplasty of Narrowed Femoropopliteal Arteries to Prevent Restenosis: Results of the PARIS Feasibility Clinical Trial

168 000 to just under