Epoetin trials: randomised controlled trials don't always mimic observational data.
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Anemia↗
Biomedical subjects
Adeera Levin
Publications and source records attributed to Adeera Levin.
Evaluation of predictive formulae for glomerular filtration rate for carboplatin dosing in gynecological malignancies.
OBJECTIVES: Carboplatin dosing is usually based on glomerular filtration rate (GFR). The Cockcroft-Gault and the Modified Diet in Renal Disease (MDRD) Study formulae are based on serum creatinine to estimate GFR when measured GFR is impractical. The MDRD formula has been shown to be more accurate in non-cancer patients with chronic renal disease. We compared the accuracy of these formulae for dosing carboplatin in patients with gynecological cancers. METHODS: Patient data were collected retrospectively at the Vancouver Centre of the British Columbia Cancer Agency, Canada. GFR estimated by formula was compared to measured GFR. Dose derived from estimated GFR was compared to dose derived from measured GFR. Bias (percentage error) and precision (absolute percentage error) were compared with two-sided paired t-test. RESULTS: A total of 96 patients were evaluable: median age 60 years, weight 62 kg, height 159 cm, baseline serum creatinine 71 micromol/l, GFR 91 ml/min. Both formulae had limited precision with a small bias for estimated GFR and dosing. Eight-five percent of patients would have received a significantly different dose if estimated GFR from any formula was used. The MDRD formula was more precise than the Cockcroft-Gault formula. CONCLUSIONS: The MDRD formula seems to be more accurate than the Cockcroft-Gault formula in this population. However, both have limited precision and measured GFR should be preferred for carboplatin dosing.
Adult↗
Anemia and the heart in chronic kidney disease.
Cardiovascular disease is highly prevalent at all stages of chronic kidney disease (CKD) and is the leading cause of morbidity and mortality. Individuals with CKD commonly have multiple risk factors for the development of cardiovascular disease, including both traditional and nontraditional risk factors. Anemia is a nontraditional cardiovascular risk factor found in CKD that contributes to the development and progression of structural abnormalities of the heart, namely left ventricular hypertrophy and dilation. In addition, a deficiency of erythropoietin per se also may have important pathophysiologic consequences. In this review we summarize the evidence from observational studies showing an association between anemia and adverse cardiac outcomes at all stages of CKD. In addition, we provide an overview of the evidence accumulating from randomized controlled trials conducted in both nondialysis and dialysis CKD populations evaluating the effect of anemia correction on cardiac outcomes such as changes in left ventricular hypertrophy.
Anemia↗
Attitudes of Canadian nephrologists toward multidisciplinary team-based CKD clinic care.
BACKGROUND: Although evidence supporting the advantages of multidisciplinary team-based chronic kidney disease (CKD) care is not well developed, many groups are advocating increased availability of this model. METHODS: The research design is a mailed survey sent to 523 members of the Canadian and Quebec Societies of Nephrology. RESULTS: After excluding 113 respondents who declared themselves to be ineligible, the response rate was 54%. Ninety-one percent of nephrologists reported that they usually or always use a CKD clinic. Decisions about when to perform CKD-related tasks were based mainly on an estimate of glomerular filtration rate, rather than time remaining before end-stage renal disease (ESRD). The ideal creatinine clearance for referral to a CKD clinic was 30 to 59 mL/min (0.50 to 0.98 mL/s), but the usual level was 20 to 29 mL/min (0.33 to 0.44 mL/s). The ideal time for referral was more than 12 months before ESRD. Renal replacement therapy discussions were initiated at a creatinine clearance of 20 to 29 mL/min (57%). Nephrologists supported promotion of home dialysis for suitable patients, but not mandating this. Nephrologists did not provide a blunt prognosis to patients who did not specifically ask. Late referral based on adequate time for ESRD preparation was reported to be 4 to 6 months (27%), 7 to 9 months (26%), or 10 to 12 months (30%). Thirty-eight percent said that optimal preparation takes 13 months or longer. CONCLUSION: The literature's common definition of less than 3 months as a cutoff value between late and early referral is not endorsed. Given that multidisciplinary team-based care is widely available in Canada, this study might inform other jurisdictions about the merits and problems associated with multidisciplinary team-based care and might shape the agenda for future empirical research.
Attitude of Health Personnel↗
Effect of early correction of anemia on the progression of CKD.
BACKGROUND: This study is designed to assess the effect of early and complete correction of anemia by using recombinant human erythropoietin (epoetin) alfa on the progression of chronic kidney disease (CKD). METHODS: Patients were randomly assigned to achieve high (13 to 15 g/dL [130 to 150 g/L]) or low (11 to 12 g/dL [110 to 120 g/L]) hemoglobin-level targets during 4 months of stabilization, followed by 36 months of maintenance. Glomerular filtration rate (GFR) decrease was measured by using iohexol clearance. Quality of life, nutrition, and safety also were monitored. RESULTS: Because of labeling changes for subcutaneous administration of epoetin alfa (Eprex; Johnson and Johnson, Schaffhausen, Switzerland), the study was terminated prematurely. There were 195 patients enrolled in each group; 108 high-hemoglobin and 133 low-hemoglobin patients entered the maintenance phase. Mean maintenance duration was 7.4 months for the high-hemoglobin group and 8.3 months for the low-hemoglobin group. GFR decrease was numerically, but not statistically significantly, lower with the high-hemoglobin group (0.058 versus 0.081 mL/min/1.73 m2/mo [< 0.01 mL/s/1.73 m2/mo]). Physical quality-of-life measures showed trends (Role-Physical, P = 0.055; Physical Function, P = 0.083) or statistically significant improvement (Vitality, P = 0.042) with high hemoglobin levels at the end of the stabilization phase. Adverse events were similar between groups. Cardiovascular adverse events occurred in 25% of the high-hemoglobin and 18% of the low-hemoglobin patients (P = 0.137). Neither epoetin dosage nor hemoglobin level was associated with cardiovascular adverse events or death. CONCLUSION: These data suggest that normalization of hemoglobin levels in patients with CKD is safe. Longer duration studies are needed to clarify efficacy benefits with high hemoglobin levels.
Adolescent↗
Analysis of cardiovascular disease and kidney outcomes in multidisciplinary chronic kidney disease clinics: complex disease requires complex care models.
PURPOSE OF REVIEW: Chronic kidney disease is recognized as being highly prevalent in the population, and associated with morbidity and mortality relative to the general population. The complexity of patients and the multiplicity of interventions required to maintain health has forced clinicians to develop different models of healthcare delivery. This publication reviews the current literature on specific interventions to reduce progression of chronic kidney disease and cardiovascular disease, and studies the examination of outcomes of patients exposed to different healthcare delivery models. Specifically we examine the rationale and outcomes of those seen in multidisciplinary clinics. RECENT FINDINGS: Current evidence supports the use of rennin-angiotensin system blockers, reduction of blood pressure and proteinuria and phosphate control. Additional less robust studies support the need for attention to anemia, hyperparathryoidism, and other more "kidney specific" risk factors. The attendance of identified chronic kidney disease patients at multidisciplinary clinics appears to improve survival once dialysis is started. Despite aggressive management, not all patients are able to meet clinical targets associated with improved outcomes. SUMMARY: The recognition of the complexity of chronic kidney disease care and the need to develop and test models of care in addition to the single interventions is a challenge for both researchers and clinicians. Current data support the use of multidisciplinary clinics in improving outcomes of referred patients. Future research will help to refine and define appropriate care models for this growing chronic kidney disease population.
Calcium↗
Surveillance cultures of tunneled cuffed catheter exit sites in chronic hemodialysis patients are of no benefit.
Catheter-related infections are a major cause of morbidity and mortality in hemodialysis (HD) patients. This study evaluated the utility of surveillance swab cultures (Ssc) of tunneled cuffed catheter (TCC) exit sites as a prediction and prevention strategy for infection. A 6-month prospective-controlled trial with 94 chronic HD patients with a TCC who received monthly Ssc and were stratified by dialysis day into topical therapy based on Ssc results (Group A) or no therapy (Group B). Outcomes were exit site infection (ESI) and catheter-associated bacteremia (CAB). The overall monthly prevalence of positive Ssc was 14.9%. There was no difference in the number of positive Ssc (17.7% vs. 11.6%, p > 0.05) or ESI (19.6% vs.16.3%, p > 0.05) between Groups A and B, respectively. Catheter-associated bacteremia was higher in Group A (17.7% vs. 4.7%, p = 0.05). There were significantly more ESI in the patients treated for a positive Ssc. In Group A, the incidence of ESI was significantly higher in those treated for a positive vs. negative Ssc (55% vs. 12%, p = 0.009) and CAB rates trended higher with positive Ssc (22.2% vs. 16.7%, p > 0.05). The strategy of treating positive surveillance cultures is not beneficial. Positive Ssc do not predict the occurrence of catheter-related infection, and treatment of these cultures may lead to increased infection rates.
Aged↗
Kidneys, hearts, hormones and immunomodulators: integrated understandings.
The biological processes governing vascular endothelial cell health are complex and highly redundant. The mechanisms involved in cell injury and repair remain an area of intense study. This paper attempts to review current knowledge regarding hormones such as vitamin D, erythropoietin and aldosterone within the context of what we understand of the inflammatory cascade. This is not a comprehensive review of vascular biology, and many important details and background information have been omitted due to space and complexity considerations. The integration of exocrine and endocrine functions within the kidney, the intimate relationship of those functions with vascular health, and the clinical observations of high prevalence of cardiovascular disease in chronic kidney disease warrant a better understanding of this area by clinicians and basic researchers.
Cardiovascular Diseases↗
Renal safety of 1-hour pamidronate infusion for breast cancer and multiple myeloma patients: comparison between clinical trials and population-based database.
PURPOSE: The American Society of Clinical Oncology recommends infusion of pamidronate over 2 hours to avoid renal deterioration, although there are data to suggest that 1-hour infusions may be safe. METHODS: Prevalence of renal deterioration with 1-hour pamidronate infusions from a population database was compared to renal deterioration with 2-hour pamidronate infusions, in randomised, controlled, trials. A cost-minimisation analysis, comparing the 1- and 2-hour pamidronate infusions, and the 15-minute infusion of zoledronic acid, was performed with a sensitivity analysis that varied the opportunity cost of time in the treatment room. RESULTS: Renal deterioration occurred in 7.7% of 169 patients with multiple myeloma and metastatic breast cancer. There is no evidence that this differs from the 10% reported in randomised, controlled, trials (one-tailed binomial test, P = 0.3874). A subgroup analysis showed that renal deterioration occurred in 15 and 1.1% of patients with multiple myeloma and metastatic breast cancer, respectively. The median increase in serum creatinine was 13 and 7% in the multiple myeloma and breast cancer groups, respectively. The respective costs/dose (drug/labour/supplies) of pamidronate and zoledronic acid are 325 dollars and 610 dollars. Cost neutrality occurs if the opportunity cost of chair time is 6.33 dollars/minute for pamidronate 1-hour versus zoledronic acid, and 2.71 dollars/minute for pamidronate 2-hour versus zoledronic acid. If a median 4 dollars/minute is used, the respective costs of pamidronate 1-hour, 2-hour, and zoledronic acid infusions are 685 dollars, 925 dollars, and 790 dollars/cycle. CONCLUSIONS: Prevalence of renal deterioration with 1-hour pamidronate infusions from a population database was not significantly different to 2-hour pamidronate infusions in clinical trials. Our findings suggest further support for the safety of 1-hour pamidronate infusions. Pamidronate via 1-hour infusion is less expensive than zoledronic acid.
Aged↗
Kidney function and mortality among patients with left ventricular systolic dysfunction.
Kidney disease has emerged as a risk factor for mortality in heart failure populations. The objective of this study was to determine the impact of different stages of kidney dysfunction (defined using the Kidney Disease Outcomes Quality Initiative [K/DOQI] classification system) and changes in kidney function on mortality in a cohort of patients with heart failure. A retrospective analysis was conducted of data from the randomized controlled trials Studies of Left Ventricular Dysfunction. A total of 6640 participants with asymptomatic and symptomatic heart failure were studied. Estimated GFR (eGFR) were calculated and then categorized according to the K/DOQI classification system into the following categories: > or =90, 60 to 89, 30 to 59, and 15 to 29 ml/min per 1.73 m2. Reduction in eGFR from baseline was calculated and subsequently categorized according to rate of decline (<5, 5 to 10, 11 to 15, and >15 ml/min per 1.73 m2 per year). Independent of baseline differences, lower levels of eGFR were associated with a higher total mortality compared with those with eGFR > or =90 ml/min (30 to 59 ml/min per 1.73 m2: hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.10 to 1.59, P = 0.004; 15 to 29 ml/min per 1.73 m2: HR 2.54, 95% CI 1.54 to 4.19, P < 0.001). eGFR deteriorated rapidly (>15 ml/min per 1.73 m2 per year) in 12% of participants. This decline was associated with a significant increase in mortality compared with slower decline (<5 ml/min per 1.73 m2 per year), despite adjustments for baseline kidney function, baseline heart failure, or change in heart failure (HR 5.63; 95% CI 4.90 to 6.46; P < 0.0001). The levels of eGFR from the K/DOQI classification system are associated with mortality in a well-characterized heart failure population. Rate of decline in kidney function is a strong predictor of increased mortality in this population, independent of worsening heart failure and baseline kidney function.
Adult↗
Prognostic value of troponin T and I among asymptomatic patients with end-stage renal disease: a meta-analysis.
BACKGROUND: The prognostic usefulness of troponin enzymes in end-stage renal disease (ESRD) patients is controversial. To resolve this uncertainty of troponin as a prognostic tool, we conducted a systematic review to quantify the association between elevated troponin I or T and long-term total mortality among ESRD patients not suspected of having acute coronary syndrome. METHODS AND RESULTS: We conducted an unrestricted search from the MEDLINE, EMBASE, and DARE bibliographic databases to December 2004 using the terms troponin.mp. or exp troponin and exp kidney, exp renal, exp kidney disease exp renal replacement therapy. We also manually searched review articles and bibliographies to supplement the search. Studies were included if they were prospective observational studies, used cardiac-specific troponin assays, and evaluated long-term risk of death or cardiac events for asymptomatic ESRD patients. Two authors independently abstracted data on study and patient characteristics. Studies findings were stratified according to troponin T or I levels. We used a random-effects model to pool study results and tested for heterogeneity using chi2 testing and used funnel-plot inspection to evaluate the presence of publication bias. Data from 28 studies (3931 patients) published between 1999 and December 2004 were included in this review. Patients received dialysis for a median duration of 4 years, with a mean follow-up of 23 months. From the pooled analysis, elevated troponin T (>0.1 ng/mL) was significantly associated with increased all-cause mortality (relative risk, 2.64; 95% CI, 2.17 to 3.20). Although the prognostic effect sizes were all consistent with a positive relationship between troponin T and mortality, there was significant heterogeneity in the magnitude of these effect sizes (P=0.015). The funnel plot showed evidence of publication bias. Elevated troponin T was also strongly associated with increased cardiac death. Studies evaluating troponin I included a wide variety of assays and differing cut points, rendering synthesis of the study findings difficult. CONCLUSIONS: Elevated troponin T (>0.1 ng/mL) identifies a subgroup of ESRD patients who have poor survival and a high risk of cardiac death despite being asymptomatic. These findings suggest that troponin T is a promising risk stratification tool and may help frame therapeutic decisions. The clinical interpretation of elevated troponin I levels, however, remain unclear, largely because of the lack of standardization of assays.
Biomarkers↗
Haemoglobin at time of referral prior to dialysis predicts survival: an association of haemoglobin with long-term outcomes.
Haemoglobin (Hgb) levels are known to be associated with numerous adverse outcomes in both chronic kidney disease (CKD) and non-CKD patients. This analysis evaluates the association of baseline haemoglobin levels on survival in CKD patients, who are followed by nephrologists, irrespective of glomerular filtration rate (GFR), prior to initiation of renal replacement therapy (RRT) and erythropoietin hormone replacement therapy. Analysis of data from the provincial database (PROMIS, Patient Registration and Outcome Management Information System) in British Columbia, Canada, was undertaken. Records used for the analysis included all CKD patients at first registration: GFR <60 ml/min/1.73 m(2), not yet on dialysis, starting from May 1998 to October 2002, and who had complete data (defined as age and gender, diabetic status, eGFR and Hgb levels). The primary objective of this study was to determine the association of Hgb and survival controlling for eGFR at first registration value, age, gender and diabetic status. Multivariate Cox proportional hazards analysis with time to death as outcome variable was performed. The cohort included 3028 patients: the mean age was 65 years, 28% were diabetic, and the mean eGFR in the cohort was 21 ml/min/1.73 m(2). The cohort is representative of the BC CKD and dialysis population regarding ethnicity: 64% Caucasian, 32% Asian. Median follow-up was 27 months, 1 year survival was 0.92, 2 year survival was 0.85. Hgb at initial registration is a statistically independent predictor of survival (RR = 0.875 for every 10 g/l, 95% CI: 0.835-0.917, P = 0.0001), after adjusting for age, gender, diabetic status and baseline eGFR. Further analysis, controlling for RRT, demonstrated a similar association between Hgb and survival (RR = 0.853 for every 10 g/l, 95% CI: 0.799-0.910, P = 0.0001), after adjusting for above variables. Substantial variation in Hgb values exists at all GFR levels. These findings underscore the importance of evaluating Hgb at all GFR levels, and the need to study the impact of modification of Hgb at different GFR levels on survival.
Aged↗
Successful reintroduction of a different erythropoiesis-stimulating agent after pure red cell aplasia: relapse after successful therapy with prednisone.
We report a 3-year case history that describes a 78-year-old woman with recurrent transfusion-dependent pure red cell aplasia (PRCA) secondary to recombinant epoetin use that was responsive to immunosuppressant therapy. The patient had kidney disease of unknown aetiology (estimated glomerular filtration rate of 13 ml/min/1.73 m2) and was not on dialysis. After 16 months of therapy with subcutaneous Eprex, she developed anti-erythropoietin antibody-confirmed PRCA and was started on high dose prednisone (50 mg per day). Within 5 months, the patient's serum was clear of antibodies and, under the cover of low dose prednisone (5-7.5 mg per day), therapy with a different erythropoiesis-stimulating compound (Aranesp) was initiated due to persistent fatigue and anaemia. At 3 months of therapy, the serum anti-erythropoietin antibodies remained negative and, due to the patient's requests, and after discussion, prednisone therapy was discontinued. Unfortunately, 3 months after cessation of prednisone, a recurrence of PRCA was confirmed by the development of profound anaemia and reappearance of anti-erythropoietin antibodies in the patient's serum. High dose prednisone (50 mg per day) was reinstituted, whereupon, 2 months later, antibodies were again confirmed to be negative. This case report demonstrates the responsiveness of PRCA to simple immunosuppressive therapy, and the ability to introduce different erythropoiesis-stimulating agents in the presence of such therapy. It appears that there may be problems associated with discontinuation of immunosuppressive therapy in the presence of sustained erythropoiesis-stimulating agent therapy in those in whom the condition has occurred previously.
Aged↗
Cystatin C, serum creatinine, and estimates of kidney function: searching for better measures of kidney function and cardiovascular risk.
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Biomarkers↗
Cardiovascular events and investigation in patients who are awaiting cadaveric kidney transplantation.
The optimal strategy for cardiovascular (CV) disease surveillance in kidney transplant candidates is uncertain. In this observational study of 604 wait-listed patients in British Columbia, the risk for CV event in diabetic and nondiabetic candidates was 12.7 and 4.5% per year, respectively. CV event rates were relatively constant during the first 3 yr of wait-listing (5.3 to 6.6 per 100 patient-years; 95% confidence interval [CI], 3.7 to 9.3) but rose dramatically during the peritransplantation period (39.6/100 patient-years; 95% CI, 20.6 to 76.1) and remained high throughout the first posttransplantation year (4.0 per 100 patient-years; 95% CI, 2.2 to 7.5). The results of noninvasive cardiac investigations before wait-listing were not predictive of the time to CV event after wait-listing. The practice of surveillance cardiac investigation in wait-listed patients on the basis of ongoing clinical assessment of cardiac risk resulted in fewer investigations (n = 171) than with the recommended practice of periodic screening on the basis of waiting time alone (n = 530) and was not associated with an increased frequency of CV events (CV event rate in patients with and without the recommended frequency of investigation was 9.9 [95% CI, 7.1 to 13.7] and 6.7 [95% CI, 5.2 to 8.7] per 100 patient-years). It is concluded that transplant candidates are at high risk for CV events particularly during the perioperative period. Initial cardiac investigations have limited value in guiding the timing of patient reevaluation after wait-listing. Periodic surveillance cardiac investigation after wait-listing may be unnecessary and requires further study.
Adult↗
C-reactive protein levels in patients on maintenance hemodialysis: reliability and reflection on the utility of single measurements.
BACKGROUND: Single C-reactive protein (CRP) values have been associated with death and cardiovascular disease in dialysis patients. We prospectively obtained multiple CRP values in stable patients, hypothesizing that values would remain stable in the absence of disease and that a single CRP value would be a reliable marker of risk. METHODS: Four CRP values per week for three consecutive weeks were obtained in 10 clinically stable patients receiving conventional HD. Using prespecified cutoffs of 2.2 and 4.4 mg/l, the frequency of risk misclassification relative to the lowest CRP value obtained was determined. Within and between patient variability was also calculated. RESULTS: The median age was 54 years, and the average duration of dialysis was 41 months. Nine out of ten patients had at least one abnormal CRP value (>2.2 mg/l), six had all values elevated, and seven had an abnormal median CRP. The overall coefficient of reliability was 0.63 (95% CI 0.42-0.87). The misclassification rate varied with cutoff, and ranged from 0-83% and 0-58% using upper limit of normal (ULN) and twice ULN, respectively. The within patient variability was 0.37 for the entire cohort, and 0.33 when three patients with intercurrent acute inflammation were excluded. CONCLUSIONS: CRP exhibits short term variability in HD patients, resulting in a risk of misclassification depending on sampling time and chosen cutoff point. Single CRP values must be interpreted with caution, and multiple measurements, or use of other biomarkers, should be considered.
Aged↗
Executing change in the management of chronic kidney disease: perspectives on guidelines and practice.
In this era of escalating information, costly technology, and an increasing prevalence of chronic complex diseases in an aging population, a systematic approach to execute changes in the care of patients with kidney disease must be developed. Specifically, there is a need to facilitate the translation of research and clinical guidelines into the delivery of quality clinical care. At present in nephrology, there is some knowledge of disease processes, accumulating knowledge about risk factors for progression, and knowledge about how to best deliver care to those with a chronic disease. The current health care environment is not suited to either the care of chronic conditions or to prevention. Information technology should facilitate shared models of care delivery for chronic conditions and allow opportunities to add new knowledge and deliver good care to complex patient groups. To execute change in the management of patients with CKD, medical students, healthcare professionals, and established physicians need to be educated about the prevalence and consequences of CKD. These educational initiatives should be done in the context of cases or specific patients especially for established practitioners, and should be simplified to make analogies to familiar concepts. The concept that CKD is a risk factor for cardiovascular disease, and needs to be managed (as does diabetes and dyslipidemia), should be more clearly articulated. Basic and clinical research in kidney disease has been enhanced by discoveries in vascular biology, diabetes, and cardiology. Much of the clinical research has been limited, however, by lack of clear definition of CKD. The development of the new K/DOQI staging system that defines and classifies the severity of kidney disease may improve the execution of ongoing robust clinical trials. Incorporating this classification system into the clinical practice of all physicians by automatic laboratory reporting of estimates of GFR raises awareness and improves communication between all medical professionals. Collaborative management of CKD patients between different physicians and multidisciplinary teams, in conjunction with the ongoing investigation of treatments and treatment strategies by both clinician and researchers, may well lead to improved outcomes for patients with CKD. Executing change in the management of CKD requires an increased awareness on the part of all clinicians, including nephrologists, regarding the prevalence and importance of the problem of earlier stages of kidney disease. The systematic evaluation of all patients and incorporation of simplified definitions and classification systems should enhance the ability to improve the outcomes of patients with kidney disease irrespective of time of identification.
Guideline Adherence↗
Multiple risk factor intervention in chronic kidney disease: management of cardiac disease in chronic kidney disease patients.
This article describes the relationship between CVD and CKD, the current state of knowledge regarding medical interventions, and underscores the importance of attending to both CVD and kidney disease aspects in each individual. The burden of cardiac disease in CKD patients is high with severe LVH, dilated cardiomyopathy and coronary artery disease occurring frequently. This predisposes to congestive heart failure, angina, myocardial infarction, and death. Multiple risk factors for cardiac disease exist and include hypertension, diabetes, smoking, anemia, abnormal calcium and phosphate metabolism, inflammation, and LVH. The efficacy of risk factor intervention has not been established in these populations, although there is good evidence for good blood pressure control, partial correction of anemia, treatment of dyslipidemia, cessation of tobacco use, correction of divalent abnormalities, and aspirin us. Appropriate use of ACE inhibitors, beta-blockers, and statins should be encouraged.
Cardiovascular Diseases↗