Lipoprotein-Associated Phospholipase A2, Vascular Inflammation and Cardiovascular Risk Prediction

Circulating lipoprotein-associated phospholipase A2 (Lp-PLA2) is a marker of inflammation that plays a critical role in atherogenesis; its inhibition may have antiatherogenic effects. Studies from the West of Scotland Coronary Prevention Study (WOSCOPS), Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) and Rotterdam cohorts have shown that Lp-PLA2 is an independent predictor of coronary heart disease (CHD), and the association is not attenuated upon multivariate analysis with traditional risk factors and other inflammatory markers. Studies in subjects with coronary artery disease (CAD) have also shown associations between Lp-PLA2 and cardiovascular risk. At least two recent studies have shown that Lp-PLA2 is a risk predictor for stroke. Overall, epidemiological studies suggest that measurement of Lp-PLA2 in plasma may be a useful in identifying individuals at high risk for cardiovascular events

729-2 Macrophage-Monocyte Invasion is Associated with Greater Cardiac Hypertrophy in Hypertensive Rats

Cardiac hypertrophy is an adaptive response to increased wall stress in hypertension. Although the mechanisms underlying this adaptive response are not clearly understood, a genetic predisposition appears to playa role. We sought to examine the hypothesis that an inflammatory response occurs in the heart early in the course of development of hypertension. We measured blood pressure, heart weight and cardiac macrophage-monocyte invasion in 6 week old SHR and WKY rats with renal hypertension (1 Kidney-1 Clip, 1K1C) or sham-operated controls (SHAM). Macrocyte-monophage invasion was measured as the extent of immunohistochemical staining with ED1, a cytoplasmic antigen in this cell type. Measurements were made at 7 and 21 days post procedure. Renal hypertensive rats, both SHR and WKY, had higher blood pressures at both time points than SHR sham, which in turn had higher blood pressures that WKY sham rats. Heart weight/body weight ratios were highest in SHR-1 K1 C rats, followed by SHR SHAM and WKY 1K1C, and least in WKY sham rats. ED1 staining was also highest in SHR 1K-lC rats, followed by SHR sham rats, and was considerably lower in WKY rats, 1K-1C or sham. Data atthe 21 day time point are shown below:BP (mmHg)Heart wt/body wt (mg/g)ED1 (counts/HPF)SHR 1K1C2054.320.0SHR SHAM1703.415.0WKY 1K1C2033.712.5WKY SHAM1432.812.5Thus, significant monocyte-macrophage invasion is a hitherto unrecognized feature of cardiac hypertrophy in SHR rats. We speculate that growth factors released by such cells may contribute to hypertensive cardiac hypertrophy

Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: Evidence for late reinnervation

Objectives.This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation.Background.Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied <6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur >1 year after transplantation.Methods.We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (<-1 year) and late (>1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation.Results.No subject had visible I-123 MIBG uptake on imaging <1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake.Conclusions.Sympathetic reinnervation of the transplanted human heart can occur >1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure

Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: Correlation with high density lipoproteins

AbstractObjectives. This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultraound imaging.Background. Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis.Methods. Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque.Results. Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [±SD] 0.25 ± 0.16) than in the left main (0.11 ± 0.16, p < 0.001) and iliac arteries (0.02 ± 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index ⪰0.42 (left anterior descending artery) and ⪰0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery.Conclusions. In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease

Randomized Comparison of Everolimus- and Paclitaxel-Eluting Stents 2-Year Follow-Up From the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) IV Trial

ObjectivesWe sought to determine whether the differences in outcomes present between everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) IV trial at 1 year were sustained with longer-term follow-up.BackgroundIn the SPIRIT IV trial, patients undergoing percutaneous coronary intervention who were randomized to EES compared with PES experienced lower 1-year rates of target lesion failure (cardiac death, target vessel myocardial infarction [MI], or ischemia-driven target lesion revascularization [TLR]), with significant reductions in the individual rates of MI, TLR, and stent thrombosis.MethodsWe prospectively randomized 3,687 patients with up to 3 noncomplex previously untreated native coronary artery lesions to EES versus PES at 66 U.S. sites. Follow-up through 2 years is complete in 3,578 patents (97.0%).ResultsTreatment with EES compared with PES reduced the 2-year rates of TLF (6.9% vs. 9.9%, p = 0.003), all MI (2.5% vs. 3.9%, p = 0.02), Q-wave MI (0.1% vs. 0.8%, p = 0.002), stent thrombosis (0.4% vs. 1.2%, p = 0.008), and ischemia-driven TLR (4.5% vs. 6.9%, p = 0.004), with nonsignificantly different rates of all-cause and cardiac mortality. Between 1 year and 2 years, there were no significant differences in adverse event rates between the 2 stent types.ConclusionsIn the large-scale, prospective, multicenter, randomized SPIRIT IV trial, the benefits of EES compared with those of PES present at 1 year were sustained at 2 years. (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System; NCT01016041