Safety of iodinated intravenous contrast medium administration in sickle cell disease.

BACKGROUND: Increased sickling of erythrocytes following intravenous iodinated contrast has been described in patients with sickle cell disease. In vitro, the effect is correlated with the tonicity, viscosity, acidity, and ionic nature of contrast media. Less erythrocyte sickling is observed in vitro with second-generation low- and iso-osmolar contrast agents. Clinical impact of these newer intravenous contrast agents has not been investigated. PURPOSE: To review adverse outcomes following contrast administration in a cohort of patients with sickle cell disease. METHODS: Inpatients with sickle cell disease who received iodinated intravenous were identified. Medical records were reviewed for evidence of worsening crisis and occurrence of adverse events within 48 hours of contrast administration. Data points were further analyzed with the goal of identifying predictors of adverse outcome. RESULTS: There were 132 imaging studies that met inclusion criteria in 79 patients, mostly with homozygous hemoglobin S. The low-osmolar contrast Optiray (Coviden Imaging Inc., Hazelwood, Mo) was used in 45%. Administration of fluids, Mucomyst (Bristol-Myers Squibb, New York, NY), oxygen, or blood transfusion preceded 58% of studies. Minor adverse events followed 16% of studies, with new or worsening pain being most common (12%). Contrast-induced nephropathy occurred in 1.5%, resolving in all cases. Prehydration was associated with a decreased incidence of adverse events (P=.02). CONCLUSION: Adverse events related to intravenous contrast occur in sickle cell disease patients at a rate similar to the general population, without an increase in contrast-induced nephropathy. Subjective reports of new or worsening pain crisis do not translate to objective findings. Beneficial diagnostic imaging can be performed without increased risk of serious complication in this population.

Management of clopidogrel hypersensitivity without drug interruption.

Clopidogrel hypersensitivity affects up to 6% of treated patients, often leading to discontinuation of the drug. Conventional desensitization protocols incorporate a washout period off medication that may be problematic after percutaneous coronary intervention because premature discontinuation of dual antiplatelet therapy is a major risk factor for stent thrombosis. The purpose of this study was to evaluate a strategy for treating clopidogrel hypersensitivity without drug interruption using corticosteroids and antihistamines to facilitate development of physiologic tolerance. The study population consisted of 25 consecutive patients who developed clopidogrel hypersensitivity after percutaneous coronary intervention and were managed with suppressive therapy using corticosteroids and antihistamines. Treatment success (resolution of hypersensitivity symptoms without interrupting clopidogrel) was assessed, in addition to duration of clopidogrel therapy and adverse cardiac events during late follow-up (mean 670 ± 630 days). The cohort included 19 men and 6 women with a mean age of 62 ± 9 years. Drug-eluting stents were used in 16 patients (64%). Clopidogrel hypersensitivity occurred 6 ± 2 days after drug initiation. Treatment included corticosteroids (5 patients), antihistamines (5 patients), or corticosteroids and antihistamines (15 patients). Patients treated with corticosteroids received tapering courses for a mean of 10 ± 8 days. Treatment was successful with sustained symptom resolution in 22 of 25 patients (88%). Clopidogrel therapy was continued in successfully desensitized patients for 417 ± 369 days and in patients with drug-eluting stents for 529 ± 376 days. There were no deaths, myocardial infarctions, or stent thrombosis during extended follow-up. In conclusion, clopidogrel hypersensitivity can be successfully treated using short-course corticosteroids and antihistamines without interrupting drug therapy. This technique enables long-term continuation of clopidogrel and confers a low risk of adverse cardiac events.

Clopidogrel hypersensitivity: clinical challenges and options for management.

Over 90 million patients have been prescribed clopidogrel since its US FDA approval in 1997. Clopidogrel hypersensitivity affects up to 6% of patients, most commonly in the form of a pruritic rash. Symptoms are severe enough to result in drug discontinuation in 1.5% of patients. Premature discontinuation of clopidogrel is problematic following percutaneous coronary intervention because of the risk of stent thrombosis leading to myocardial infarction and death. Accordingly, the management of patients with clopidogrel hypersensitivity is of significant clinical importance. Conventional clopidogrel desensitization protocols, while successful in most patients, employ a washout period off medication to enable accurate detection of a reaction during the desensitization. However, interruption of therapy is potentially hazardous in patients with recent stent placement. Our clinical experience demonstrates that clopidogrel hypersensitivity can be successfully treated without drug interruption using short-course corticosteroids and antihistamines to enable the development of physiologic tolerance while the medication is continued. The role of newer agents, such as prasugrel, as surrogate therapy in patients with clopidogrel hypersensitivity is yet to be defined.

Correlation of oral glucose tolerance test-derived estimates of insulin sensitivity with insulin clamp measurements in an African-American cohort.

The purpose of this study was to determine which measures obtained from an oral glucose tolerance test (OGTT) are the best estimates of insulin sensitivity measured directly using the euglycemic hyperinsulinemic clamp procedure. Data were examined from a study conducted on 307 young adult African-American men and women. An OGTT with insulin measurements was conducted after a 12-hour overnight fast. The euglycemic hyperinsulinemic clamp was used to measure insulin-stimulated glucose uptake (M) directly. Pearson's correlation analyses were performed to examine the relationship of OGTT-derived parameters with insulin sensitivity measured using the clamp. There were consistent statistically significant correlations between calculated estimates of insulin sensitivity (fasting insulin/fasting glucose, summed insulin/summed glucose, homeostasis model assessment [HOMA], Quantitative Insulin Sensitivity Check Index [QUICKI]) with insulin sensitivity measured by the insulin clamp (P <.001). The calculated estimates that correlated most strongly with clamp measured insulin sensitivity were QUICKI and the logarithm of summed insulin during the OGTT. These data indicate that fasting and OGTT-derived plasma insulin and glucose concentrations can be used to estimate insulin sensitivity in young adult African-Americans when it is not feasible to conduct the insulin clamp procedure. Calculated indices that include log transformation of plasma insulin concentration improve the estimation of insulin sensitivity.

Obesity and high blood pressure: a clinical phenotype for the insulin resistance syndrome in African Americans.

The high prevalence of insulin resistance syndrome in African Americans predisposes this population to higher morbidity and mortality from cardiovascular disease. To test the hypothesis that the combination of obesity and high blood pressure (BP) represents the physical phenotype of insulin resistance syndrome, 337 African-American men and women aged 32+/-4 years were examined and classified into four groups (nonobese-normal BP, nonobese-high BP, obese-normal BP, obese-high BP), according to presence or absence of obesity and high BP. Mean values of glucose, insulin, lipids, urinary albumin excretion, and clamp-derived insulin sensitivity were determined for each group. Prevalence of prediabetes (24.4%), diabetes (19.2%), and insulin resistance syndrome (87.2%) were highest in the obese-high BP group (p<0.001). Mean triglycerides, urinary albumin excretion, fasting glucose, fasting insulin, and insulin resistance were highest in the obese-high BP group (p<0.001). Subjects with both obesity and high BP showed greater expression of lipid and glucose abnormalities, higher urinary albumin excretion, and greater prevalence of prediabetes, undetected type 2 diabetes, and insulin resistance syndrome.

Obesity, smoking, and multiple cardiovascular risk factors in young adult African Americans.

OBJECTIVES: To examine the associations between the combination of obesity and tobacco use and total cardiovascular risk score in young adult African Americans. DESIGN: A cross-sectional study of 323 African-American men (N = 117) and women (N = 206) aged 20-46 years. METHODS: Age, height, weight, and data on smoking behavior were obtained, as well as measurements of blood pressure, serum lipids, and measurements from an oral glucose tolerance test (OGTT). A cardiovascular risk score was calculated from the above data. RESULTS: Fasting insulin, fasting blood glucose, and blood glucose at 120 minutes of OGTT were significantly higher in obese (body mass index [BMI] > or = 30 kg/m2) men. Obese men also had significantly higher LDL cholesterol, lower HDL cholesterol and higher total risk scores. Obese women had significantly higher blood pressure, higher fasting insulin, lower LDL cholesterol, and higher total risk scores. Among the members of this cohort, 65% of men and 79% of women were obese and/or smoked. Of those who were obese and/or smoked, 68% of the men and 82% of the women had at least one other cardiovascular risk factor. CONCLUSIONS: The modifiable risk factors of obesity and smoking were present in a large majority of these young adult African Americans in association with other cardiovascular risk factors.

Glucose tolerance and cardiovascular risk in young adult African Americans.

BACKGROUND: Patients with type 2 diabetes have higher rates of cardiovascular events. Among African Americans, there is a higher prevalence of both cardiovascular disease and type 2 diabetes. Few studies have examined longitudinally the change in glucose tolerance in younger adult African Americans. METHODS: To examine the longitudinal relationship of glucose tolerance with other cardiovascular risk factors, 30 African American men and women aged 20 to 43 years were examined twice at an interval of 4 to 5 years. Cardiovascular risk factors, glucose tolerance, and insulin sensitivity (determined from euglycemic hyperinsulinemic clamp procedure) were assessed at each examination. Known diabetics were excluded from initial enrollment. The relationship of glucose tolerance status (normal, impaired, or diabetic glucose tolerance) to body mass index, blood pressure, cholesterol, and insulin sensitivity were further investigated. RESULTS: Initial oral glucose tolerance test identified 24 of 130 (18.5%) subjects with impaired glucose tolerance and 2 of 130 (1.5%) subjects with diabetes. Of the remaining 104 subjects with normal glucose tolerance, subsequent 5-year examination detected 31 (29.8%) with impaired glucose tolerance and 5 (4.8%) with diabetes. Those who later developed diabetes had higher mean systolic blood pressure (133 versus 121, P = 0.037) at exam 1. By exam 2, those with abnormal glucose tolerance had worse cardiovascular risk profiles and increased insulin resistance (P < 0.001). CONCLUSION: Conversion to abnormal glucose tolerance is relatively frequent in young adult African Americans. Deterioration in glucose tolerance may be preceded by higher systolic blood pressure and is accompanied by worsening of other cardiovascular risk factors and insulin resistance.

The association between hypertension and other cardiovascular risk factors in young adult African Americans.

Hypertension is a major cause of cardiovascular disease in African Americans. The excess morbidity and mortality due to cardiovascular disease in African Americans compared to Caucasians is not well explained. The purpose of this study was to examine the association between hypertension and other cardiovascular risk factors in young adult African Americans. A risk factor scoring system was developed, based on national guidelines for obesity, smoking, cholesterol levels, glucose tolerance, and blood pressure. Data from a previously studied cohort of 206 women and 117 men were analyzed for the association of hypertension with other risk factors. Among women, risk factor intensification is due to impaired glucose tolerance and obesity. Among men, intensification appears to be related to all major risk factor categories. These findings indicate that among hypertensive African Americans there is an amplification of other risk factors. The data also support the clinical management of multiple risk factors as well as the achievement of blood pressure control.