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Biomedical subjects

Peter A McCullough

Publications and source records attributed to Peter A McCullough.

At least 19 recordsLinked to original sources
PubMed2007

Statin therapy in renal disease: harmful or protective?

Chronic kidney disease (CKD) creates one of the highest-risk atherosclerotic states that can occur in human beings. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has gained widespread acceptance in the general population for the purposes of lowering low-density lipoprotein cholesterol (LDL-C) and reducing the future risks of myocardial infarction, stroke, and cardiac death. In patients with CKD, these benefits are believed to be enjoyed to the same or greater degrees. Reductions in LDL-C with statins may be associated with a reduced progression of CKD. Importantly, recent studies suggest statins are associated with a reduction in rates of acute renal failure after cardiopulmonary bypass surgery and exposure to iodinated contrast. In patients with end-stage renal disease (ESRD), recent data suggest that the annual rate of coronary artery calcification can be attenuated or reduced with LDL-C reduction. However, two large trials demonstrating LDL-C reduction with statins and with these drugs have failed to demonstrate a reduction in cardiovascular events in ESRD. Thus, the potential benefits of statins and LDL-C reduction in CKD have to be considered in light of evidence suggesting a reduced benefit if any, in patients with ESRD. In addition, studies suggest that there are higher adverse drug effects with statins in CKD.

Acute Kidney Injury↗
PubMed2006

Reduction in predicted coronary heart disease risk after substantial weight reduction after bariatric surgery.

In recent years, bariatric surgery has become an increasingly used therapeutic option for morbid obesity. The effect of weight loss after bariatric surgery on the predicted risk of coronary heart disease (CHD) has not previously been studied. We evaluated baseline (preoperative) and follow-up (postoperative) body mass index, CHD risk factors, and Framingham risk scores (FRSs) for 109 consecutive patients with morbid obesity who lost weight after laparoscopic Roux-en-Y gastric bypass surgery. Charts were abstracted using a case-report form by a reviewer blinded to the FRS results. The study included 82 women (75%) and 27 men (25%) (mean age 46 +/- 10 years). Mean body mass index values at baseline and follow-up were 49 +/- 8 and 36 +/- 8 kg/m(2), respectively (p <0.0001). During an average follow-up of 17 months, diabetes, hypertension, and dyslipidemia resolved or improved after weight loss. Thus, the risks of CHD as predicted by FRS decreased by 39% in men and 25% in women. The predicted 10-year CHD risks at baseline and follow-up were 6 +/- 5% and 4 +/- 3%, respectively (p < or =0.0001). For those without CHD, men compared favorably with the age-matched general population, with a final 10-year risk of 5 +/- 4% versus an expected risk of 11 +/- 6% (p <0.0001). Likewise, women achieved a level below the age-adjusted expected 10-year risk of the general population, with a final risk of 3 +/- 3% versus 6 +/- 4% (p <0.0001). In conclusion, weight loss results in a significant decrease in FRS 10-year predicted CHD risk. Bariatric surgery decreases CHD risk to rates lower than the age- and gender-adjusted estimates for the general population. These data suggest substantial and sustained weight loss after bariatric surgery may be a powerful intervention to decrease future rates of myocardial infarction and death in the morbidly obese.

Bariatric Surgery↗
PubMed2006

Caloric expenditure in the morbidly obese using dual energy X-ray absorptiometry.

Total caloric expenditure is the sum of resting energy expenditure (REE) and caloric expenditure during physical activity. In this study, we examined total caloric expenditure in 25 morbidly obese patients (body mass index>or=35 kg/m(2)) using dual energy X-ray absorptiometry (DXA) scanning and cardiorespiratory exercise testing. Our results show average REE for all individuals was 2027+/-276 kcal/d and mean net caloric expenditure during 30 min of exercise was 115+/-16 kcals. Assuming the mean of all input values, a strict 1500 kcal/d diet combined with 150 min per wk of structured physical activity, the projected weight change was -7% (8.8+/-6.2 kg) for 6 mo. We conclude that morbidly obese individuals should be able to achieve only a modest weight loss by following minimal national guidelines. These data suggest that more aggressive energy expenditure and caloric restriction targets for long periods of time are needed to result in significant weight loss in this population.

Absorptiometry, Photon↗
PubMed2006

A meta-analysis of the renal safety of isosmolar iodixanol compared with low-osmolar contrast media.

OBJECTIVES: We sought to compare the nephrotoxicity of isosmolar contrast medium (IOCM) iodixanol with low-osmolar contrast media (LOCM) and to identify predictors of contrast-induced nephropathy (CIN). BACKGROUND: Contrast-induced nephropathy is a serious complication of diagnostic and interventional procedures. METHODS: Pooled individual patient data (n = 2,727) from 16 double-blind, randomized, controlled trials in which patients received either intra-arterial IOCM iodixanol (n = 1,382) or LOCM (n = 1,345) were included. Patients were stratified according to chronic kidney disease (CKD), diabetes mellitus (DM), or both. Outcome measures were the maximum increase in serum creatinine (Cr) over baseline and the incidence of postprocedural CIN. RESULTS: The maximum Cr increase within 3 days after contrast medium (CM) administration was significantly smaller in the iodixanol group compared with the LOCM group (0.06 mg/dl vs. 0.10 mg/dl, p < 0.001), particularly in patients with CKD (0.07 mg/dl vs. 0.16 mg/dl, p = 0.004) and CKD + DM (0.10 mg/dl vs. 0.33 mg/dl, p = 0.003). Contrast-induced nephropathy, defined as an increase in Cr > or =0.50 mg/dl within 3 days after CM administration, occurred less frequently in the iodixanol group than in the LOCM group in all patients (1.4% vs. 3.5%, p < 0.001), in CKD patients (2.8% vs. 8.4%, p = 0.001), and in CKD + DM patients (3.5% vs. 15.5%, p = 0.003). Independent predictors of CIN included CKD, CKD + DM, and use of LOCM. CONCLUSIONS: This meta-analysis of pooled data from 2,727 patients indicates that use of the IOCM iodixanol is associated with smaller rises in Cr and lower rates of CIN than LOCM, especially in patients with CKD or CKD + DM.

Contrast Media↗
PubMed2006

Strategies to reduce the risk of contrast-induced nephropathy.

In view of the clinical importance of contrast-induced nephropathy (CIN), numerous potential risk-reduction strategies have been evaluated. Adequate intravenous volume expansion with isotonic crystalloid (1.0-1.5 mL/kg per hr) for 3-12 hours before the procedure and continued for 6-24 hours afterward can lessen the probability of CIN in patients at risk. There are insufficient data on oral fluids (as opposed to intravenous volume expansion) as a CIN-prevention strategy. No adjunctive medical or mechanical treatment has been proved to be efficacious in reducing risk for CIN. Prophylactic hemodialysis and hemofiltration have not been validated as effective strategies. The CIN Consensus Working Panel considered that, of the pharmacologic agents that have been evaluated, theophylline, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), ascorbic acid, and prostaglandin E(1) deserve further evaluation. N-acetylcysteine is not consistently effective in reducing the risk for CIN. Fenoldopam, dopamine, calcium channel blockers, atrial natriuretic peptide, and l-arginine have not been shown to be effective. Use of furosemide, mannitol, or an endothelin receptor antagonist is potentially detrimental. Nephrotoxic drugs should be withdrawn before contrast administration in patients at risk for CIN.

Acute Kidney Injury↗
PubMed2006

Contrast medium use.

Various properties of iodinated contrast media (osmolality, ionic versus nonionic, and viscosity) may contribute to contrast-induced nephropathy (CIN). Therefore, the choice of contrast medium affects the risk for CIN. There is good evidence that low-osmolar contrast media are less nephrotoxic than high-osmolar contrast media in patients at increased risk for CIN who receive intra-arterial iodinated contrast. Current evidence suggests that nonionic isosmolar contrast presents the lowest risk for CIN in patients with chronic kidney disease (CKD), particularly in those patients with diabetes mellitus. Intra-arterial administration of contrast media may be associated with a greater risk for CIN above that observed with intravenous administration. The use of gadolinium or CO(2) as alternative contrast media to avoid the risk of nephrotoxicity cannot be substantiated by clinical trials and therefore cannot be recommended. Most studies show that, within a class, higher volumes (>100 mL) of iodinated contrast medium are associated with a higher risk for CIN. However, in patients at high risk, such as those with CKD and diabetes, even small volumes of contrast medium can have adverse effects on renal function.

Acute Kidney Injury↗
PubMed2006

Risk prediction of contrast-induced nephropathy.

In order to make appropriate decisions about clinical management, it is important for physicians to be able to stratify patients according to their risk for contrast-induced nephropathy (CIN). The most important risk marker for nephropathy after exposure to iodinated contrast media is preexisting renal impairment. The risk of CIN is elevated and becomes clinically important in patients with chronic kidney disease characterized by an estimated glomerular filtration rate <60 mL/min per 1.73 m(2). In patients with renal impairment, diabetes mellitus amplifies the risk of CIN and complicates postprocedure management. Other markers associated with an increased risk of CIN include cardiovascular disease, periprocedural hemodynamic instability, use of nephrotoxic drugs, and anemia. The effect of risk factors is additive, and the presence of multiple risk factors in the same patient can create a very high risk for CIN and acute renal failure requiring dialysis. Risk models incorporating baseline and periprocedural characteristics have been developed using data from large databases of percutaneous coronary intervention patients. These schemes are potentially valuable, but at present the most practical approach to risk prediction is based on a simple model incorporating renal function and diabetes mellitus.

Cardiovascular Diseases↗
PubMed2006

Baseline renal function screening.

Renal impairment at baseline (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2)) is the most important risk marker to predict the risk of contrast-induced nephropathy (CIN) in patients receiving iodinated contrast media. Hence, it is important to assess renal function before administration of contrast medium to ensure that appropriate steps are taken to reduce the risk. Serum creatinine alone does not provide a reliable measure of renal function, hence the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) recommends that clinicians should use an eGFR calculated from the serum creatinine as an index of renal function. The CIN Consensus Working Panel agreed that eGFR should be determined before contrast administration, using the abbreviated Modification of Diet in Renal Disease (MDRD) formula, recommended by K/DOQI as the preferred equation for the calculation of eGFR in adults. Where a serum creatinine measurement or eGFR is not available, a simple survey or questionnaire can be used before contrast agent administration to identify patients at higher risk for CIN compared with the general population. In emergency situations, where the benefit of very early imaging outweighs the risk of waiting, the CIN Consensus Working Panel agreed that the procedure can be performed without assessment of renal function.

Consensus Statements as Topic↗
PubMed2006

High-risk situations and procedures.

With the wider use of imaging and interventional techniques that require the use of iodinated contrast media in seriously ill patients, many clinical situations occur where patients may be at increased risk for contrast-induced nephropathy (CIN). There is little guidance for clinicians in these areas. The aim of this review is to assess the available literature. Acute renal failure is a common complication following coronary artery bypass surgery, and exposure to contrast medium may increase the risk for this condition, although there is insufficient evidence to make a definitive statement. Evidence is also limited for patients with liver disease: in those undergoing transarterial chemoembolization, cirrhosis may be a risk factor for renal failure. There is some evidence that periprocedural hypotension may be a risk factor for CIN after percutaneous coronary intervention, but no published information was identified on the significance of shock or hypotension in other groups of patients. The published evidence on the risk of CIN in renal transplant recipients is inconsistent. In emergency situations, the course of action is usually dictated by clinical circumstances; the renal status of a patient is likely to be unknown and it is important to ensure adequate volume expansion, especially after the procedure. In all clinical situations that are potentially associated with a high risk for CIN, the decision to administer contrast medium is a matter for clinical judgment, based on the clinical status of the patient and the expected benefits of the investigation or procedure.

Acute Kidney Injury↗
PubMed2006

Pathophysiology of contrast-induced nephropathy.

Contrast-induced nephropathy (CIN) is the third leading cause of acute kidney injury in hospitalized patients and is associated with significant patient morbidity. The pathogenesis of CIN is complex and not fully understood, but iodinated contrast agents induce intense and prolonged vasoconstriction at the corticomedullary junction of the kidney. Moreover, high-osmolar dyes directly impair the autoregulatory capacity of the kidney through a loss of nitric oxide production. These effects, coupled with direct tubular toxicity of contrast media, lead to overt acute tubular necrosis and the syndrome of CIN.

Acute Kidney Injury↗
PubMed2006

Epidemiology and prognostic implications of contrast-induced nephropathy.

Contrast-induced nephropathy (CIN), usually defined as an increase in serum creatinine of 0.5 mg/dL (44.2 mumol/L), or a 25% increase from the baseline value 48 hours after the procedure, is a common and potentially serious complication of the use of iodinated contrast media in patients at risk of acute renal injury. It is an important cause of hospital-acquired renal failure, responsible for approximately 11% of cases. CIN may be difficult to distinguish from cholesterol embolization, another cause of postprocedure renal impairment. The reported incidence of CIN varies depending on the patient population studied. The impact of postprocedural renal impairment on clinical outcomes has been evaluated most extensively in patients undergoing percutaneous coronary intervention. CIN is associated with increased mortality both in hospital and at 1 year. A higher incidence of in-hospital and late cardiovascular events, as well as longer hospital stays, has been reported in patients developing CIN. In a small proportion of patients, CIN is severe enough to require dialysis, and these patients have a particularly poor prognosis. Many of the risk markers for CIN are also predictive of a worse prognosis.

Acute Kidney Injury↗
PubMed2006

Impact of body mass index on outcomes of enhanced external counterpulsation therapy.

OBJECTIVES: We evaluated the association of baseline body mass index (BMI) on the outcomes of enhanced external counterpulsation (EECP) therapy for chronic stable angina. BACKGROUND: We are in the midst of a pandemic of obesity, which is complicating the care of patients with coronary artery disease (CAD). METHODS: We examined 2730 patients enrolled from 2002 to 2004 in the IEPR-2. Baseline and outcome variables were stratified by the entry BMI in kilograms per meter squared. RESULTS: Obesity (BMI > 30 kg/m2) was common (40.6%) among patients with severe CAD referred for EECP. Within the total cohort, 2.6% was underweight (BMI < or = 20 kg/m2) and 4.5% was morbidly obese (BMI > 40 kg/m2). Prevalence of diabetes, hypertension, dyslipidemia, and heart failure (HF) was higher in obese patients. However, the rates of baseline angina and prior revascularization were similar among the groups. The peak diastolic augmentation ratio was similar between groups during the first (0.7 +/- 0.4 for lowest and highest BMI) and last hours of treatment (0.9 +/- 0.5 and 0.8 +/- 0.5). The cumulative hours of treatment, the change in angina class, and the Duke Activity Status Index were similar for all BMI groups. There was a greater reduction in weekly anginal episodes from baseline across ascending levels of BMI (-6.3 +/- 13.6 to -9.7 +/- 15.8, P = .03). The rates of discontinuation for clinical events were highest (14.3%) with skin breakdown being the most frequent cause (10.1%) in the underweight. The rates of clinical events including myocardial infarction, HF, and death trended higher across ascending levels of BMI (P = .52). Multivariate analysis found that older age, history of stroke, history of HF, and diabetes, but not BMI, were predictors of clinical events. CONCLUSIONS: More than 40% of patients with severe CAD referred for EECP were obese. Underweight patients had higher rates of discontinuation of treatment mainly because of skin breakdown. Symptomatic benefit of EECP was similar among all BMI groups. However, despite symptomatic improvement, there was a nonsignificant trend for higher rates of myocardial infarction, HF, and death as BMI increased.

Aged↗
PubMed2006

How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study.

BACKGROUND: B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNP > or = 100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis. METHODS: The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results. RESULTS: Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively (P < .05 for all comparisons except 35 vs 25). B-type natriuretic peptide cut-points to maintain 90% sensitivity for a HF diagnosis were 170 pg/mL for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL in severely/morbidly obese patients. CONCLUSIONS: Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP > or = 54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNP > or = 170 pg/mL) could be used to increase specificity.

Acute Disease↗
PubMed2006

Gray zone BNP levels in heart failure patients in the emergency department: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study.

OBJECTIVES: The study purpose was to examine "gray zone" B-type natriuretic peptide (BNP) levels (100-500 pg/mL) in terms of associated clinical factors, perceived severity, and outcomes in patients with established congestive heart failure (CHF). BACKGROUND: Although gray zone BNP levels may have diagnostic ambiguity, the implications of these levels in patients with an established diagnosis of CHF have not been examined. METHODS: REDHOT was a national prospective study in which 464 patients seen in the emergency department with dyspnea had BNP levels drawn. Entrance criteria included a BNP > 100 pg/mL; however, physicians were blinded to the actual BNP level. Patients were followed up for 90 days. RESULTS: Thirty-three percent had gray zone BNP levels. There was no difference in perceived New York Heart Association class (P = .32) or admission rates (P = .76) between the gray zone and non-gray zone groups; 62% of patients with a gray zone BNP were identified as class III or IV CHF. Despite this perceived severity, the 90-day event rate was lower in the gray zone group (19.2% vs 32.9%, respectively, P = .002). Although patients in the gray zone had more symptoms of concomitant pulmonary disease, multivariate analysis could not demonstrate any variable that worsened the prognosis of patients with a gray zone BNP level. CONCLUSIONS: In patients with established CHF, those with gray zone BNP levels have a better prognosis than those with non-gray zone levels despite being perceived by physicians as having New York Heart Association class III or IV CHF.

Aged↗
PubMed2006

Impact of the history of congestive heart failure on the utility of B-type natriuretic peptide in the emergency diagnosis of heart failure: results from the Breathing Not Properly Multinational Study.

PURPOSE: B-type natriuretic peptide is known to correlate with hemodynamic state, presence and severity of congestive heart failure, and prognosis. Although low-range B-type natriuretic peptide less than 100 pg/mL has a high negative predictive value (90%), and high-range B-type natriuretic peptide greater than 500 pg/mL has a high positive predictive value (87%), there remains some ambiguity in the interpretation of results in the medium range (100-500 pg/mL). We hypothesized that taking into account the history of congestive heart failure along with other clinical variables would be helpful in this range of B-type natriuretic peptide levels. METHOD: The Breathing Not Properly Multicenter Study was an international, 7-center, prospective study including 1475 patients with a mean age of 63 years (57% were male, and 54% were female); 35% of patients with a history of congestive heart failure were enrolled, and a final diagnosis of congestive heart failure was made in 46%. The index criteria was defined as positive if any 2 index findings (ie, history of coronary artery disease, lower extremity edema, pulmonary edema, cephalization of the pulmonary arteries, and cardiomegaly) were present. RESULTS: The interval likelihood ratios (LR) for low, medium, and high B-type natriuretic peptide ranges are 0.13, 1.85, and 8.1, respectively. For medium B-type natriuretic peptide levels a positive history of congestive heart failure makes the diagnosis of congestive heart failure more probable with a cumulative LR of 4.3. Also in this range a positive index criterion was strongly indicative of congestive heart failure even in the absence of a history of congestive heart failure (LR 3.3). Where there are both a positive history of congestive heart failure and a positive index criteria for the medium B-type natriuretic peptide group, the cumulative LR (10.2) is similar to that of a high B-type natriuretic peptide level (8.1). CONCLUSION: Even in the medium range (100-500 pg/mL), when using the history of congestive heart failure and index criteria, B-type natriuretic peptide can be a powerful diagnostic tool in the hands of clinicians in the emergency department.

Aged↗
PubMed2006

B-type natriuretic peptide (BNP) levels and ethnic disparities in perceived severity of heart failure: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study of BNP levels and emergency department decision making in patients presenting with shortness of breath.

BACKGROUND: Previous studies have shown that in patients presenting to the emergency department (ED) with heart failure, there is a disconnect between the perceived severity of congestive heart failure (CHF) by physicians and the severity as determined by B-type natriuretic peptide (BNP) levels. Whether ethnicity plays a role in this discrepancy is unknown. METHODS AND RESULTS: The Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) was a 10-center trial of 464 patients seen in the ED with acute dyspnea and BNP level higher than 100 pg/mL on arrival. Physicians were blinded to BNP levels. Patients were followed for 90 days after discharge. A total of 151 patients identified themselves as white (32.5%) and 294 as black (63.4%). Of these, 90% were hospitalized. African Americans were more likely to be perceived as New York Heart Association class I or II than whites (P = .01). Blacks who were discharged from the ED had higher median BNP levels than whites who were discharged (1293 vs. 533, P = .004). The median BNP of blacks who were discharged was actually higher than the median BNP of blacks who were admitted (1293 vs. 769, P = .04); the same did not hold true for whites. BNP was predictive of 90-day outcome in both blacks and whites; however, perceived severity of CHF, race, and ED disposition did not contribute to the prediction of events. CONCLUSION: In patients presenting to the ED with heart failure, the disconnect between perceived severity of CHF and severity as determined by BNP levels is most pronounced in African Americans.

Black or African American↗