Atherogenic lipid phenotype in a general group of subjects.

CONTEXT: The atherogenic lipid phenotype is a major cardiovascular risk factor, but normal values do not exist derived from 1 analysis in a general study group. OBJECTIVE: To determine normal values of all of the atherogenic lipid phenotype parameters using subjects from a general study group. DESIGN: One hundred two general subjects were used to determine their atherogenic lipid phenotype using polyacrylamide gradient gels. RESULTS: Low-density lipoprotein (LDL) size revealed 24% of subjects express LDL phenotype B, defined as average LDL peak particle size 258 A or less; however, among the Chinese subjects, the expression of the B phenotype was higher at 44% (P = .02). For the total group, mean LDL size was 265 +/- 11 A (1 SD); however, histograms were bimodal in both men and women. After excluding subjects expressing LDL phenotype B, because they are at increased cardiovascular risk and thus are not completely healthy, LDL histograms were unimodal and the mean LDL size was 270 +/- 7 A. A small, dense LDL concentration histogram (total group) revealed skewing; thus, phenotype B subjects were excluded, for the rationale described previously, and the mean value was 13 +/- 9 mg/dL (0.33 +/- 0.23 mmol/L). High-density lipoprotein (HDL) cholesterol histograms were bimodal in both sexes. After removing subjects as described previously or if HDL cholesterol levels were less than 45 mg/dL, histograms were unimodal and revealed a mean HDL cholesterol value of 61 +/- 12 mg/dL (1.56 +/- 0.31 mmol/L). HDL 2, HDL 2a, and HDL 2b were similarly evaluated. CONCLUSIONS: Approximate normal values for the atherogenic lipid phenotype, similar to those derived from cardiovascular endpoint trials, can be determined if those high proportions of subjects with dyslipidemic cardiovascular risk are excluded.

Extended-release niacin treatment of the atherogenic lipid profile and lipoprotein(a) in diabetes.

We tested the hypotheses that extended-release niacin is effective for the separate treatments of abnormalities in low-density liprotein (LDL) size, high-density lipoprotein (HDL)-2, and lipoprotein(a) [Lp(a)] without potential negative effects on glycated hemoglobin levels. The lipids that constitute the atherogenic lipid profile (ALP), such as triglycerides, small, dense LDL-cholesterol particle concentration, LDL particle size, total HDL-cholesterol (HDLc), HDL-2, and HDL-2 cholesterol concentration, as well as total LDL-cholesterol (LDLc) and Lp(a), were measured in 36 diabetic patients with primary abnormalities of LDL particle size (n = 25), HDL-2 (n = 23), and/or Lp(a) (n = 12) before and after extended-release niacin treatment. LDL particle size and HDL-2 were measured using polyacrylamide gradient gel electrophoreses and Lp(a) was measured by enzyme-linked immunosorbent assay (ELISA). After extended-release niacin, LDL peak particle diameter increased from 25.2 +/- 0.6 nm to 26.1 +/- 0.7 nm (P <.0001); small, dense LDLc concentration decreased from 30 +/- 17 mg/dL to 17 +/- 10 mg/dL (P <.0001); total HDLc increased from 42 +/- 9 mg/dL to 57 +/- 16 mg/dL (P <.0001); HDL-2 as the percent of total HDLc mass increased from 34% +/- 10% to 51% +/- 17% (P <.0001); and Lp(a) decreased from 37 +/- 10 mg/dL to 23 +/- 10 mg/dL (P <.001). Mean hemoglobin A(1c) level was improved during treatment from 7.5% +/- 1.6% to 6.5% +/- 0.9% (P <.0001). A subset of patients who had no change in hemoglobin A(1c) levels before and after treatment (6.8% +/- 1% v 6.7% +/- 1%; not significant) showed identical lipid changes. Twenty-two percent of patients were unable to tolerate extended-release niacin due to reversible side effects. These data indicate that in diabetic patients, extended-release niacin (1) is effective for separately treating diabetic dyslipidemias associated with abnormal LDL size, HDL-2, and Lp(a) independently of glycated hemoglobin levels; (2) must be used with modern and aggressive oral hypoglycemic agents or insulin treatment; and (3) is a major drug for the treatment of diabetic dyslipidemias because of its broad spectrum of effectiveness for the ALP and Lp(a).