Alan K. Berger

Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO)

Cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) is high, and the presence of CKD worsens outcomes of cardiovascular disease (CVD). CKD is associated with specific risk factors. Emerging evidence indicates that the pathology and manifestation of CVD differ in the presence of CKD. During a clinical update conference convened by the Kidney Disease: Improving Global Outcomes (KDIGO), an international group of experts defined the current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death. Although optimal strategies for prevention, diagnosis, and management of these complications likely should be modified in the presence of CKD, the evidence base for decision making is limited. Trials targeting CVD in patients with CKD have a large potential to improve outcomes.

Aspirin, beta-blocker, and angiotensin-converting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction

OBJECTIVES We sought to examine the use and impact of standard medical therapies in patients with end-stage renal disease (ESRD) faced with an acute myocardial infarction (AMI). BACKGROUND The poor prognosis of patients in this high-risk population has become increasingly well recognized. METHODS Using the ESRD database and the Cooperative Cardiovascular Project (CCP) database, we identified AMI patients who were receiving either peritoneal dialysis or hemodialysis before admission. The early administration of aspirin and beta-blockers was compared between ESRD and non-ESRD patients and the effect of these therapies on 30-day mortality was evaluated with logistic regression models. RESULTS The cohort consisted of 145,740 patients without ESRD and 1,025 patients with ESRD. Aspirin (67.0% vs. 82.4%, p < 0.001), beta-blockers (43.2% vs. 50.8%, p < 0.001), and angiotensin-converting enzyme (ACE) inhibitors (38.5% vs. 60.3%, p < 0.001) were less likely to be administered to ESRD patients than to non-ESRD patients. The benefit of these therapies on 30-day mortality was similar among ESRD patients (aspirin: relative risk [RR] 0.64; 95% confidence interval [CI] 0.50 to 0.80; beta-blocker: RR 0.78; 95% CI 0.60 to 0.99; ACE inhibitor: RR 0.58; 95% CI 0.42 to 0.77) and non-ESRD patients (aspirin: RR 0.57; 95% CI 0.55 to 0.58; beta-blocker: RR 0.70; 95% CI 0.68 to 0.72; ACE inhibitor: RR 0.64; 95% CI 0.63 to 0.66). CONCLUSIONS End-stage renal disease patients are far less likely than non-ESRD patients to be treated with aspirin, beta-blockers, and ACE inhibitors during an admission for AMI. The lower rates of usage for these medications, particularly aspirin, may contribute to the increased 30-day mortality. These findings demonstrate a marked opportunity to improve care in this population.

Acute Myocardial Infarction Complicated by Atrial Fibrillation in the Elderly Prevalence and Outcomes

BACKGROUND Although atrial fibrillation (AF) is a common complication of acute myocardial infarction (MI), patient characteristics and association with outcomes remain poorly defined in the elderly. METHODS AND RESULTS We evaluated 106 780 Medicare beneficiaries > or =65 years of age from the Cooperative Cardiovascular Project treated for acute MI between January 1994 and February 1996 to determine the prevalence and prognostic significance of AF complicating acute MI in elderly patients. Patients were categorized on the basis of the presence of AF, and those with AF were further subdivided by time of AF (present on arrival versus developing during hospitalization). AF and non-AF patients were compared by univariate analysis, and logistic regression modeling was used to identify clinical predictors of AF. The influence of AF on outcomes was evaluated by unadjusted Kaplan-Meier survival curves and logistic regression models. AF was documented in 23 565 patients (22. 1%): 11 510 presented with AF and 12,055 developed AF during hospitalization. AF patients were older, had more advanced heart failure, and were more likely to have had a prior MI and undergone coronary revascularization. AF patients had poorer outcomes, including higher in-hospital (25.3% versus 16.0%), 30-day (29.3% versus 19.1%), and 1-year (48.3% versus 32.7%) mortality. AF remained an independent predictor of in-hospital (odds ratio [OR], 1. 21), 30-day (OR, 1.20), and 1-year (OR, 1.34) mortality after multivariate adjustment. Patients developing AF during hospitalization had a worse prognosis than patients who presented with AF. CONCLUSIONS AF is a common complication of acute MI in elderly patients and independently influences mortality, particularly when it develops during hospitalization.

Race, sex, poverty, and the medical treatment of acute myocardial infarction in the elderly

BACKGROUND Race, sex, and poverty are associated with the use of diagnostic cardiac catheterization and coronary revascularization during treatment of acute myocardial infarction (AMI). However, the association of sociodemographic characteristics with the use of less costly, more readily available medical therapies remains poorly characterized. METHODS AND RESULTS We evaluated 169 079 Medicare beneficiaries >/=65 years of age treated for AMI between January 1994 and February 1996 to determine the association of patient race, sex, and poverty with the use of medical therapy. Multivariable regression models were constructed to evaluate the unadjusted and adjusted influence of sociodemographic characteristics on the use of 2 admission (aspirin, reperfusion) and 2 discharge therapies (aspirin, beta-blockers) indicated during the treatment of AMI. Therapy use varied by patient race, sex, and poverty status. Black patients were less likely to undergo reperfusion (RR 0.84, 95% CI 0. 78, 0.91) or receive aspirin on admission (RR 0.97, 95% CI 0.96, 0. 99) and beta-blockers (RR 0.94, 95% CI 0.88, 1.00) at discharge. Female patients were less likely to receive aspirin on admission (RR 0.98, 95% CI 0.97, 0.99) and discharge (RR 0.98, 95% CI 0.96, 0.99). Poor patients were less likely to receive aspirin (RR 0.97, 95% CI 0. 96, 0.98) or reperfusion (RR 0.97, 95% CI 0.93, 1.00) on admission and aspirin (RR 0.98, 95% CI 0.96, 1.00), or beta-blockers (RR 0.95, 95% CI 0.91, 0.99) on discharge. CONCLUSIONS Medical therapies are currently underused in the treatment of black, female, and poor patients with AMI.

Thrombolytic therapy in older patients.

OBJECTIVES We compared outcomes following thrombolytic therapy and primary angioplasty with no reperfusion therapy in a population-based cohort of older patients presenting with acute myocardial infarction (AMI) and indications for acute reperfusion. BACKGROUND Evidence supporting the efficacy of acute reperfusion (thrombolytic therapy or primary angioplasty) in the elderly with suspected AMI is not as strong as it is in younger groups. METHODS From a national cohort of Medicare beneficiaries with AMI, we identified 37,983 patients age 65 or older who presented within 12 h of symptom onset with ST elevation or left bundle branch block. A total of 14,341 (37.8%) received thrombolytic therapy and 1,599 (4.2%) underwent primary angioplasty within 6 h of hospital arrival. RESULTS After adjustment for demographic, clinical, hospital and physician factors, and co-interventions, thrombolytic therapy was not associated with a better 30-day survival (odds ratio [OR] 1.01; 95% confidence interval [CI]: 0.94 to 1.09) compared with no therapy, whereas primary angioplasty was (OR 0.79; 95% CI: 0.66 to 0.94). At one year, both thrombolytic therapy (OR 0.84; 95% CI: 0.79 to 0.89) and primary angioplasty (OR 0.71; 95% CI: 0.61 to 0.83) were associated with a survival benefit. CONCLUSIONS In this national sample of older patients, those who received thrombolytic therapy or primary angioplasty had lower mortality at one year compared with those who did not receive a reperfusion strategy. However, only primary angioplasty was associated with better survival at 30 days. Our findings should heighten interest in further investigating the best approach to the treatment of older patients with suspected AMI and ST segment elevation or left bundle branch block.

Pulse pressure and risk of cardiovascular events in the systolic hypertension in the elderly program

Pulse pressure has been related to higher risk of cardiovascular events in older persons. Isolated systolic hypertension is common among the elderly and is accompanied by elevated pulse pressure. Treatment of isolated systolic hypertension may further increase pulse pressure if diastolic pressure is lowered to a greater extent than systolic pressure. Little is known regarding pulse pressure as a predictor of cardiovascular outcomes in elderly persons with isolated systolic hypertension, and the influence of treatment on the pulse pressure effect. We assessed the relation between pulse pressure, measured throughout the follow-up period, and the incidence of coronary heart disease (CHD), heart failure (HF), and stroke in 4,632 participants in the Systolic Hypertension in the Elderly Program, a 5-year randomized, placebo-controlled clinical trial of treatment of isolated systolic hypertension in older adults. In the treatment group, a 10-mm Hg increase in pulse pressure was associated with a statistically significant 32% increase in risk of HF and a 24% increase in risk of stroke after controlling for systolic blood pressure and other known risk factors, as well as with a 23% increase in risk of HF and a 19% increase in risk of stroke after controlling for diastolic blood pressure and other risk factors. Pulse pressure was not significantly associated with HF or stroke in the placebo group, nor with incidence of CHD in either the placebo or treatment group. These results suggest that pulse pressure is a useful marker of risk for HF and stroke among older adults being treated for isolated systolic hypertension.

Gender disparity in cardiac procedures and medication use for acute myocardial infarction.

OBJECTIVE Determine if gender bias is present in contemporary management of acute myocardial infarction (AMI). BACKGROUND Despite major advances in medicine, disparities in healthcare still persist. Previous studies on gender bias in the diagnosis and treatment of AMI are inconsistent and may not represent more contemporary practice. METHODS AND RESULTS Data were collected from the Minnesota Heart Survey, a population-based study of patients presenting with AMI in 2001-02. In-hospital diagnostic and therapeutic approaches were compared between women and men using logistic regression models. We identified 1242 women and 1378 men with an AMI defined by either positive cardiac biomarkers or ST-elevation on electrocardiogram. There were no differences in the prescription of aspirin, beta-blockers, ACE inhibitors or angiotensin receptor blockers. Women were 46% less likely than men to undergo investigative coronary angiography [OR = 0.54 (0.45-0.64)]. After accounting for confounders, women remained less likely to be referred for angiography [OR = 0.73 (0.57-0.94)]. Revascularization rates, were similar between women and men [OR = 0.96 (0.72-1.28)]. However, women were more likely to undergo PCI [OR = 1.41 (1.07-1.86)] whereas men were more likely to have coronary artery bypass grafting (CABG) [OR = 0.57 (0.39-0.84)]. When severity of coronary artery disease (CAD) was incorporated into the model, gender no longer influenced the modality of coronary revascularization. CONCLUSIONS There is no evidence of gender bias in the pharmacologic treatment of AMI. Evidence of gender bias persists in the referral of patients for coronary angiography but not in the subsequent use of coronary revascularization.

The combination of propranolol and magnesium does not prevent postoperative atrial fibrillation

BACKGROUND Atrial fibrillation is a common complication of cardiovascular surgery. Beta-blockers have been shown to decrease the incidence of postoperative atrial fibrillation. However, the use of magnesium is more controversial. It was our hypothesis that adjunctive magnesium sulfate would improve the efficacy of beta-blockers alone in the prevention of postoperative atrial fibrillation. METHODS We prospectively randomized 167 coronary artery bypass patients (mean age 61+/-10 years, 115 men) to receive propranolol alone (20 mg four times daily) or propranolol and magnesium (18 g over 24 hours). Magnesium was begun intraoperatively, and propranolol was started on admission to the intensive care unit. RESULTS Using an intention-to-treat analysis, the incidence of postoperative atrial fibrillation was 19.5% in the propranolol-treated patients and 22.4% in propranolol + magnesium-treated patients (p = 0.65). Because combination therapy resulted in an excess of postoperative hypotension, which required withholding doses of propranolol, an on-treatment analysis was also performed. In this analysis, the incidence of atrial fibrillation was still not significantly different (18.5% in propranolol-treated patients and 10.0% in propranolol + magnesium-treated patients, p = 0.20). CONCLUSIONS Adjunctive magnesium sulfate, in combination with propranolol, does not decrease the incidence of postoperative atrial fibrillation.

Effect of diabetes mellitus and insulin use on survival after acute myocardial infarction in the elderly (The Cooperative Cardiovascular Project)

Using data from a retrospective cohort study of Medicare beneficiaries hospitalized with an acute myocardial infarction (AMI), we evaluated the role of diabetes mellitus on 30-day and 1-year mortality. We classified subjects as nondiabetics, diabetics controlled with diet alone, diabetics receiving an oral hypoglycemic agent, and diabetics on insulin at time of admission. We compared baseline admission characteristics of subgroups using chi-square and Wilcoxon rank-sum tests and evaluated the effect of each diabetic state using sequential logistic models. We identified 80,832 nondiabetic patients, 9,862 diet-controlled diabetic patients, 14,664 diabetics receiving an oral hypoglycemic agent, and 12,241 diabetic patients on insulin therapy. Although mean age was similar among the groups, prevalence of hypertension, prior AMI, prior congestive heart failure, and prior revascularization were higher among diabetic patients, particularly those taking insulin. Diabetic patients, particularly those taking insulin, were less likely to receive aspirin and beta blockers and to undergo coronary revascularization. Diabetic patients had higher 30-day and 1-year mortality than nondiabetic patients. After adjustment for demographics, clinical and hospital characteristics, and treatment strategies, insulin-treated diabetics had the highest risk of mortality, followed by diabetics receiving oral hypoglycemic agents, followed by diet-controlled diabetics. Thus, diabetes is highly prevalent among elderly patients with an AMI. Mortality rates for these patients, particularly insulin-using diabetics, are higher than among their nondiabetic counterparts. Preventive and therapeutic strategies must be developed to ensure improved short- and long-term outcomes for elderly patients with diabetes and AMI.

Sudden cardiac death in heart failure patients with preserved ejection fraction

BACKGROUND Whereas sudden cardiac death (SCD) risk has been recognized in heart failure (HF) patients with reduced ejection fraction (HFrEF), less is known about SCD risk in HF patients with preserved EF (HFpEF). We examined the incidence and predictors of SCD in HFpEF in a large population sample. METHODS AND RESULTS Medical records of patients discharged with a primary diagnosis of HF from hospitals in Minneapolis-St Paul in 1995 and 2000 were abstracted. HFpEF was defined as EF ≥ 45%. SCD was defined as cardiac arrest or out-of-hospital death due to coronary heart disease (CHD) on death certificates. A total of 2,203 patients (age 70 ± 11 years, 53% male) were included. The 787 patients (36%) with HFpEF were older, more often female and more likely to have hypertension than the 1,416 (64%) with HFrEF. All-cause mortality (52% vs 58%; P = .01) and SCD (6% vs 14%; P < .0001) rates were lower in HFpEF than in HFrEF 5 years after hospital discharge. Age, sex, CHD, and length of index hospitalization were the only independent predictors of SCD in HFpEF. CONCLUSIONS Incidence of SCD in HFpEF is lower than in HFrEF. Present markers of SCD in HFpEF are sparse and insufficient to identify the patient at risk.