Furcy Paultre

Plasma Sphingomyelin Level as a Risk Factor for Coronary Artery Disease

Abstract—Only a fraction of the clinical complications of atherosclerosis are explained by known risk factors. Animal studies have shown that plasma sphingomyelin (SM) levels are closely related to the development of atherosclerosis. SM carried into the arterial wall on atherogenic lipoproteins may be locally hydrolyzed by sphingomyelinase, promoting lipoprotein aggregation and macrophage foam cell formation. A novel, high-throughput, enzymatic method to measure plasma SM levels has been developed. Plasma SM levels were related to the presence of coronary artery disease (CAD) in a biethnic angiographic case-control study (279 cases and 277 controls). Plasma SM levels were higher in CAD patients than in control subjects (60±29 versus 49±21 mg/dL, respectively;P <0.0001). Moreover, the ratio of SM to SM+phosphatidylcholine (PC) was also significantly higher in cases than in controls (0.33±0.13 versus 0.29±0.10, respectively;P <0.0001). Similar relationships were observed in African Americans and whites. Plasma SM levels showed a significant correlation with remnant cholesterol levels (r =0.51, P <0.0001). By use of multivariate logistic regression analysis, plasma SM levels and the SM/(SM+PC) ratio were found to have independent predictive value for CAD after adjusting for other risk factors, including remnants. The odds ratio (OR) for CAD was significantly higher for the third and fourth quartiles of plasma SM levels (OR 2.81 [95% CI 1.66 to 4.80] and OR 2.33 [95% CI 1.38 to 3.92], respectively) as well as the SM/(SM+PC) ratio (OR 1.95 [95% CI 1.10 to 3.45] and OR 2.33 [95% CI 1.34 to 4.05], respectively). The findings indicate that human plasma SM levels are positively and independently related to CAD. Plasma SM levels could be a marker for atherogenic remnant lipoprotein accumulation and may predict lipoprotein susceptibility to arterial wall sphingomyelinase.

The Use of Areas Under Curves in Diabetes Research

Recently, several articles appearing in the diabetes literature have suggested that many investigators are unclear about a number of issues involving the use of areas under the curve (AUCs). This prompted us to reconsider issues in the calculation, use, meaning, and presentation of AUCs. We discuss five issues: 1) What is a curve and an area? 2) How should one graphically present a groups curve? 3) How should one calculate AUCs? 4) Should one subtract baseline values from outcome values before calculating AUCs? And 5) are AUCs the best way to combine multiple readings into a single index?

High Levels of Lp(a) With a Small Apo(a) Isoform Are Associated With Coronary Artery Disease in African American and White Men

Abstract—Elevated levels of lipoprotein(a) [Lp(a)] and the presence of small isoforms of apolipoprotein(a) [apo(a)] have been associated with coronary artery disease (CAD) in whites but not in African Americans. Because of marked race/ethnicity differences in the distribution of Lp(a) levels across apo(a) sizes, we tested the hypothesis that apo(a) isoform size determines the association between Lp(a) and CAD. We related Lp(a) levels, apo(a) isoforms, and the levels of Lp(a) associated with different apo(a) isoforms to the presence of CAD (≥50% stenosis) in 576 white and African American men and women. Only in white men were Lp(a) levels significantly higher among patients with CAD than in those without CAD (28.4 versus 16.5 mg/dL, respectively;P =0.004), and only in this group was the presence of small apo(a) isoforms (<22 kringle 4 repeats) associated with CAD (P =0.043). Elevated Lp(a) levels (≥30 mg/dL) were found in 26% of whites and 68% of African Americans, and of those, 80% of whites but only 26% of African Americans had a small apo(a) isoform. Elevated Lp(a) levels with small apo(a) isoforms were significantly associated with CAD (P <0.01) in African American and white men but not in women. This association remained significant after adjusting for age, diabetes mellitus, smoking, hypertension, HDL cholesterol, LDL cholesterol, and triglycerides. We conclude that elevated levels of Lp(a) with small apo(a) isoforms independently predict risk for CAD in African American and white men. Our study, by determining the predictive power of Lp(a) levels combined with apo(a) isoform size, provides an explanation for the apparent lack of association of either measure alone with CAD in African Americans. Furthermore, our results suggest that small apo(a) size confers atherogenicity to Lp(a).

Is Diabetes Mellitus a Cardiovascular Disease Risk Equivalent for Fatal Stroke in Women? Data From the Women’s Pooling Project

Background and Purpose— Diabetes mellitus is an independent risk factor for stroke and is associated with a 1.8- to ≈6-fold increased risk compared with nondiabetic subjects. Recent guidelines have classified diabetes as a coronary heart disease risk equivalent. Whether diabetes is a cardiovascular disease risk equivalent for stroke is not established. Methods— Data were pooled from 9 prospective epidemiological studies in the United States. We followed up 27 269 women (8.5% diabetic, 2.9% with prior myocardial infarction, 2.3% with prior stroke) for an average of 8.3 years, during which 238 stroke deaths were observed. Results— Both diabetic subjects without cardiovascular disease and nondiabetic subjects with history of prior stroke had a significantly increased risk of 10-year stroke mortality compared with nondiabetic subjects without prior cardiovascular disease (hazard ratio [HR], 6.77; 95% confidence interval [CI], 4.56 to 10.05; HR, 3.37; 95% CI, 2.38 to 4.77). History of prior myocardial infarction was not associated with long-term stroke mortality (HR, 0.66; 95% CI, 0.27 to 1.61). After adjustment for risk factors, diabetic subjects had similar risk compared with subjects with a history of prior stroke (HR, 1.29; P =0.43). Conclusions— Diabetic subjects without cardiovascular disease have a fatal stroke risk similar to that of nondiabetic subjects with a history of prior stroke and similar risk factor profile. This suggests that diabetes mellitus may be classified as a stroke risk equivalent and may warrant more aggressive treatment strategies in the future prevention of stroke.

Association of Blood Pressure Indices and Stroke Mortality in Isolated Systolic Hypertension

Background and Purpose— Isolated systolic hypertension (ISH), systolic blood pressure (BP) ≥160 mm Hg and diastolic BP (DBP) <90 mm Hg, is associated with stroke; however, the correlation between specific BP indices and stroke mortality in ISH is not defined. Methods— In a pooled analysis of 9 epidemiological studies, we examined whether pulse pressure (PP) was more predictive of stroke mortality than systolic BP (SBP), DBP, or mean BP (MAP) in persons with ISH. Subjects (n=682; 29% male; 77% white; mean age 63.6 years) with ISH, free of cardiovascular disease, and not on antihypertensive drug therapy at baseline were followed a mean of 13.0±7.3 years, and 54 stroke deaths occurred. The relative importance of each BP index was compared by the decrease in the −2 log likelihood (a measure of model agreement with data) because of the addition of 1 or a combination of BP indices to a Cox regression model. Hazards ratios (HRs) for fatal stroke for a 1-SD in BP index were determined. Results— PP was the best predictor of stroke mortality based on the decrease in the −2 log likelihood (10.65; P=0.001; HR=1.52), followed by SBP (7.19; P=0.007; HR=1.40), DBP (2.76; P=0.10; HR=0.80), or MAP (0.39; P=0.39; HR=1.10). Any combination of BP indices did not exceed a decrease in the −2 log likelihood of 10.72. Conclusion— These data suggest that in persons with ISH, PP is a better predictor of fatal stroke than SBP, DBP, or MAP.

Usefulness of an acute coronary syndrome pathway to improve adherence to secondary prevention guidelines

tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension. J Am Coll Cardiol 1999;33:1662–1666. 11. Prescott R. The comparison of success rates in cross-over trials in the presence of an order effect. Applied Statistics 1979:9–15. 12. Grizzle J. The two-period change over design and its use in clinical trials. Biometrics 1965:467–480. 13. Hecht H, DeBord L, Sotomayor N, Shaw R, Dunlap R, Ryan C. Supine bicycle stress echocardiography: peak exercise imaging is superior to postexercise imaging. J Am Soc Echocardiogr 1993;6:265–271. 14. Coplan N, Sacknoff D, Stachenfeld N, Gleim G. Comparison of submaximal treadmill and supine bicycle exercise. Am Heart J 1994;128:416–418. 15. Ryan T, Segar D, Sawada S, Berkovitz KE, Whang D, Dohan AM, Duchak J, White TE, Foltz J, O’Donnell JA. Detection of coronary artery disease with upright bicycle exercise echocardiography. J Am Soc Echocardiogr 1993;6:186– 197. 16. Dagianti A, Penco M, Bandiera A, Sgorbini L, Fedele F. Clinical application of exercise stress echocardiography: supine bicycle or treadmill? Am J Cardiol 1998;81(suppl):62G–67G. 17. Freeman M, Berman D, Staniloff H, Elkayam U, Maddahi J, Swan H, Forrester J. Comparison of upright and supine bicycle exercise in the detection and evaluation of extent of coronary artery disease by equilibrium radionuclide ventriculography. Am Heart J 1981:182–189. 18. Buckberg GD, Fixler DE, Archie JP, Hoffman JI. Experimental subendocardial ischemia in dogs with normal coronary arteries. Circ Res 1972;30:67–81.