Autoantibodies against oxidized LDL are associated with severe chest pain attacks in patients with coronary heart disease.

Autoantibodies against oxidized low-density lipoprotein (oxLDL) predict the progression of atherosclerosis. Several studies have shown that oxLDL is present in atherosclerotic lesions and that several factors present in active atherosclerotic plaques can oxidatively modify LDL. Oxidation of LDL induces production of autoantibodies against oxLDL (oxLDLab) that can be measured using an EIA test. Our aim was to see whether oxLDLab are associated with severe chest pain attacks in coronary heart disease (CHD) patients. Patients having two- or three-vessel CHD, as assessed by coronary angiography, and their siblings were recruited into the study (n = 568, mean age 55.8 years, range 29.3-83.2 years). Nondiabetic patients having a history of severe chest pain attacks had significantly higher oxLDLab levels (0.611 +/- 0.56) than those who did not have a history of severe chest pain attacks (0.487 +/- 0.40) (p = 0.027), even though age, cholesterol level, body mass index, and blood pressure were similar in both groups. However, no difference was found in oxLDLab levels in diabetic patients with or without a history of severe chest pain attacks. Increased levels of oxLDL autoantibodies are associated with severe chest pain attacks in nondiabetic patients with CHD.

The Leu7Pro polymorphism of the neuropeptide Y gene regulates free fatty acid metabolism.

The Leu7Pro polymorphism in the signal peptide of the preproneuropeptide Y (NPY) has been associated with dyslipidemias and free fatty acid (FFA) levels during exercise. The association of this polymorphism with insulin sensitivity has not been studied. In this study, the Leu7Pro polymorphism was determined in 2 groups of nondiabetic middle-aged subjects (n = 266 and n = 295). Insulin sensitivity was measured with the hyperinsulinemic euglycemic clamp (n = 266) or with an intravenous glucose tolerance test (IVGTT, n = 295). First-phase insulin secretion was determined as insulin area under the curve (AUC) during the first 10 minutes of the IVGTT. FFAs were measured both in the fasting state and during the hyperinsulinemic clamp. The Leu7Pro polymorphism of the NPY gene was not associated with the rates of whole body glucose uptake, insulin sensitivity index, insulin secretion during the IVGTT, or insulin AUC during the oral glucose tolerance test. However, the Pro7 allele was associated with low FFA levels both in the fasting state (P =.043) and during the hyperinsulinemic clamp (P =.003). In conclusion, the Leu7Pro polymorphism of the NPY gene associates with alterations in FFA metabolism but does not have an impact on insulin sensitivity, insulin secretion, or glucose metabolism.

Cardiac adrenergic innervation is affected in asymptomatic subjects with very early stage of coronary artery disease.

UNLABELLED: The aim of this study was to investigate whether, in subjects with a very early stage of coronary artery disease without hemodynamically significant coronary artery stenoses, cardiac adrenergic innervation is already affected. METHODS: Quantitative coronary angiography and dual-isotope SPECT with 123I-metaiodobenzylguanidine (MIBG) and 99mTc-sestamibi (MIBI) were conducted to assess the function of cardiac adrenergic innervation and myocardial perfusion, respectively, in 30 asymptomatic volunteers with a high familial risk for coronary artery disease. Regional quantitative analysis of MIBG uptake and washout rates was performed using the SPECT data from the anteroseptal, lateral, and inferior myocardial regions, which represented vascular supply by the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and right coronary artery (RCA), respectively. RESULTS: The average severity of stenoses was 33% +/- 11% in the LAD, 29% +/- 14% in the LCX, and 26% +/- 19% in the RCA. The severity of stenosis was not related to MIBI uptake in any corresponding myocardial region at rest or during exercise. However, the degree of LAD stenosis correlated directly with delayed MIBG uptake (r = 0.43; P < 0.05) and inversely with MIBG washout (r = -0.34; P = 0.06) of the anteroseptal myocardium. When subjects were divided into tertiles according to the separate severity of stenosis for each coronary artery, delayed MIBG uptake in the anteroseptal region was significantly lower in the lowest LAD tertile (0.34 +/- 0.05) than in the middle (0.41 +/- 0.06; P < 0.01) or highest (0.43 +/- 0.05; P < 0.001) LAD tertile. Correspondingly, delayed MIBG uptake in the lateral region was also lower in the lowest LCX tertile than in the middle tertile (0.34 +/- 0.04 vs. 0.41 +/- 0.06, respectively; P < 0.01). Washout rate was also higher in the lowest LAD tertile (44% +/- 7%) than in the middle (36% +/- 10%; P < 0.05) or highest LAD tertile (34% +/- 8%; P < 0.01). CONCLUSION: The degree of coronary artery stenosis was associated directly with MIBG uptake and inversely with MIBG washout. This finding suggests that the function of cardiac adrenergic nerve endings is modified even in mild coronary artery disease before denervation occurs.