摘要:

The protective effect of endogenous sex hormones is commonly believed to explain the gender gap in the risk of coronary heart disease and the diminished protection in women when menopause occurs. Recent reports indicate that iron overload, due to cessation of menstrual bleeding, may be an important factor. We therefore investigated iron stores by serum ferritin measurements in healthy premenopausal (n=113) and postmenopausal (n=46) women. Ferritin levels were higher in postmenopausal than in premenopausal women, both in blood donors (43.4 versus 23.1/xg/L, f<.001) and in nondonors (71.7 versus 32.8fig/L,P< .001). Serum ferritin was positively correlated with age (r=.36,P< .001). After age adjustment, serum ferritin was positively correlated with hemoglobin, hematocrit, serum total cholesterol, and low-density lipoprotein (LDL) cholesterol. Total cholesterol was correlated with age (r=.66,/<.001), as were LDL cholesterol (r=.6O,P< .01) and high-density lipoprotein cholesterol (r=.32,P< .01). Neither ferritin nor serum lipids were directly associated with female sex hormone levels. The mutual relation between ferritin, hemoglobin, and hematocrit probably only indicates their usefulness as measures of body iron. The parallel rise in serum ferritin, total cholesterol, and LDL cholesterol might contribute to the increased risk of coronary heart disease among postmenopausal women.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Cardiovascular risk factors in men, such as cigarette smoking, hypercholesterolemia, and hypertension, also increase risk in women, but the relative susceptibility to risk factors between the sexes is not established. Our aim was to investigate a wide range of possible etiologic factors in a single population study and identify those that were more strongly related to peripheral atherosclerosis in men or women. We studied personal factors (age and social class), lifestyle factors (smoking, exercise, alcohol intake, and dietary nutrients), and intermediary factors (obesity, diabetes, serum lipids, coagulation, and rheological factors). In the Edinburgh Artery Study in 1988 we measured cardiovascular risk factors in a random population sample of 1592 men and women aged 55 to 74 years. The ankle-brachial pressure index (ABPI), which is inversely related to the degree of peripheral atherosclerosis, was assessed in each subject. Lifetime cigarette smoking was correlated with a lower ABPI equally in men and women (r= −.27,P< .001). Dietary nutrients and alcohol intake were not related differently between the sexes with ABPI. However, recall of strenuous and moderate leisure time exercise during the age range of 35 to 45 years was related more strongly to a higher ABPI in men than in women (P< .05). Plasma fibrinogen, plasma viscosity, and blood viscosity were the only intermediary factors that had stronger univariate correlations with lower ABPI in men than in women. On multivariate analysis, the sex differences persisted for plasma fibrinogen (<.05) and blood viscosity (P< .001); high-density lipoprotein cholesterol was related to ABPI in men only (sex difference,P< .1). We conclude that most lifestyle and intermediary factors were not related differently in men and women to peripheral atherosclerosis, but elevations in plasma fibrinogen and blood viscosity were each associated with a greater risk of disease in men.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Familial combined hyperlipidemia (FCHL) is an oligogenic disorder, with family members having elevated apolipoprotein B-100 levels and either elevated plasma cholesterol or triglyceride levels or both. Obligate heterozygous parents of children with lipoprotein lipase (LPL) deficiency express a mild FCHL phenotype. Of patients with FCHL, 36% have diminished postheparin LPL activity and mass values that are comparable with those of obligate heterozygotes for LPL deficiency. It is hypothesized that heterozygosity for mutations in the LPL gene could contribute to FCHL in this subset of patients. Single-strand conformation polymorphism (SSCP) analysis, direct DNA sequencing, and Southern blot analysis were used to examine exons 1 through 9 and exon-intron junctions of the LPL gene in 20 patients with FCHL and low LPL activity and mass. One subject had a substitution (GAC–>AAC) in exon 2, changing Asp to Asn. Two subjects had a previously undescribed "silent" substitution (GTG->GTA) in exon 3 at Val'06. Three patients had a premature termination at codon 447 in exon 9 resulting in truncation of the mature protein by two amino acids. In addition to SSCP analysis, exons 4,5, and 6, where almost all mutations in LPL-deficient patients have been found, were sequenced and no additional mutations were found. Southern blot analysis of the LPL gene revealed one subject with heterozygous loss of an EcoRI site but without an abnormality in Stu I restriction fragments; this mutation is therefore unlikely to be functionally significant. The substitutions identified at codons 9 and 447 have previously been found not to affect lipolytic activity when expressed in vitro. In summary, the findings suggest that mutations in the coding sequence of the LPL gene are an infrequent cause of FCHL Other mechanisms that regulate plasma LPL activity remain to be investigated in the pathogenesis of FCHL.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Individuals with elevated levels of plasma cholesterol and triglyceride may be at higher risk for coronary artery disease than those with isolated elevations of either cholesterol or triglyceride. Sequence variation in the A-I/C-IH/A-IV gene cluster has been implicated in the etiology of some disorders associated with premature atherosclerosis and/or hypertriglyceridemias with or without elevations of cholesterol. This led to the hypothesis that allelic variation at this gene locus alters plasma lipid transport and affects susceptibility for atherosclerosis. The study population, from the Atherosclerosis Risk in Communities (ARIC) Study, consisted of 50 normolipidemic individuals, 48 subjects with elevated plasma cholesterol, 47 subjects with elevated plasma triglyceride, and 123 subjects with both elevated plasma cholesterol and triglyceride who were used to evaluate associations between anXmnI polymorphic site 2.5 kilobase pairs (kbp) upstream of the structural gene for apolipoprotein (apo) A-I, intimal-medial thickening of the extracranial carotid arteries, and several plasma lipid factors. The relative allele frequencies of the 8.3-kbp allele and the 6.6-kbp allele were .86 and .14, respectively, in the entire study population and did not differ among the lipid phenotypes. In the group with elevated plasma cholesterol and triglyceride, subjects possessing the 6.6-kbp allele exhibited a greater carotid artery intimal-medial thickness (P= .034) and higher plasma levels of apoA-I, highdensity lipoprotein (HDL) cholesterol, and HDL, cholesterol (p< .02) than subjects homozygous for the 8.3-kbp allele. In contrast, subjects with the 6.6-kbp allele displayed lower mean ratios of apolipoproteins C-II to C-III, C-II to A-IV, and E to A-IV in plasma (p< .05) and a lower mean ratio of apolipoprotein C-II to C-III in the triglyceride-rich lipoproteins (P= .026). Sequence variation in or near the genes encoding apolipoproteins A-I, C-III, and A-IV may therefore identify a group of hypercholesterolemic-hypertrigtyceridernic persons who are at higher risk for atherosclerosis than others with the same lipoprotein phenotype.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The National Cholesterol Education Program (NCEP) recommends that dietary total fat, saturated fat, and cholesterol intake be reduced to £30% of calories, <10% of calories, and <300 mg/d, respectively (step 1 diet), in the general population to reduce plasma low-density lipoprotein cholesterol (LDL-C) levels and heart disease risk. We examined the LDL-C-lowering response to such a diet (26% fat, 8% saturated fat, and 201 mg/d cholesterol) compared with an average American diet (39% fat, 15% saturated fat, and 435 mg cholesterol/d) in 153 subjects using diet periods of 4 through 24 weeks for each diet phase. The mean LDL-C reduction was 13% in men (n=93) and 7% in postmenopausal women (n=60). The effect of apolipoprotein (apo) A-IV phenotype on responsiveness was examined. LDL-C lowering in men was significantly (P< .005) less (7%) for 17 apoA-IV (1/2) subjects than for 76 apoA-IV (1/1) subjects (16%). In women, 7% lowering was observed in both 12 apoA-IV (1/2) subjects and 48 apoA-IV (1/1) subjects. ApoA-FV phenotype had a significant effect on plasma high-density lipoprotein cholesterol levels during both dietary periods; women carrying the apoA-IV-2 allele had higher levels than those homozygous for the apoA-IV-1 allele. The opposite was true for triglyceride levels, but only during the period when the subjects consumed the high-fat, high-cholesterol diet. These data indicated that apoA-IV phenotype modulates the LDL-C-lowering response to a diet meeting NCEP step 1 criteria in men and that high-density lipoprotein cholesterol and triglyceride levels are affected by this locus in women.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We attempted to ascertain the effects of polyunsaturated fatty acids by conducting two studies in normal young men, in which monounsaturated fats were replaced by polyunsaturated fats within the guidelines of the American Heart Association step 1 diet. Study A employed a randomized parallel design in which subjects first consumed an average American diet (AAD) containing 37% of calories as fat (saturated fat, 16% calories; monounsaturated fat, 14% calories; and polyunsaturated fat, 7% calories). After 3 weeks, one third of the subjects continued with the AAD, one third switched to a step 1 diet in which total fat calories were reduced to 30% by replacing saturated fat with carbohydrate, and one third switched to a polyunsaturated fat-enriched (Poly) diet with the same 30% fat calories and a reduction of monounsaturated fat from 14% to 8% and an increase of polyunsaturated fat from 7% to 13% of calories. The randomized period lasted 6 weeks. Total and low-density lipoprotein (LDL) cholesterol levels on the step 1 and Poly diets were reduced compared with levels on the AAD (P< .001). Total and LDL cholesterol did not differ between the step 1 and Poly diets, although comparison between the two diets is limited by the small study groups. Serum apolipoprotein (apo) B levels fell on the Poly diet compared with the AAD. Total highdensity lipoprotein (HDL), HDL2, and HDL, cholesterol levels were not significantly affected by the diets. Postprandial lipid and lipoprotein concentrations did not significantly differ either. In study B, a randomized crossover design was used in which all subjects ate the step 1 and Poly diets for 5 weeks each with a 4-day break between diets. In the eight subjects studied, the values for fasting plasma total, LDL, and HDL cholesterol; triglycerides; apoB; and apoA-I were essentially identical at the end of each diet period. Postprandial triglyceride areas obtained after ingestion of a large, standard fat load were also the same. Finally, LDL apoB and HDL apoA-I turnovers were unaffected by replacement of monounsaturates with polyunsaturates. In summary our results indicate that modest exchanges of monounsaturated for polyunsaturated fats do not significantly affect LDL or HDL levels or metabolism, which supports the view that reducing saturated fats is the key to lowering total and LDL cholesterol.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Human low-density lipoproteins (LDLs) comprise a spectrum of particles that vary in size, density, chemical composition, metabolic behavior, and atherogenicity. To identify determinants of this heterogeneity, we measured the percent distribution and plasma concentration of the three major LDL subtractions in 34 young healthy subjects. These parameters were correlated in univariate and multivariate analyses with various body and lifestyle factors; plasma lipids and lipoprotein; and the activities of cholestcryl ester transfer protein, lipoprotein lipase, and hepatic lipase (HL). Women (n=15) had significantly more large, buoyant LDL (LDL-I; density, 1.025 to 1.034 g/mL) and high-density lipoprotein2(HDL2) than men (n=19). Both the percentage and concentration of LDL-I were correlated negatively with very-lowdensity lipoprotein triglycerides (VLDL-TG) and HL; they were correlated positively with HDL-cholesterol (HDL-C) and HDL2. In addition, percent LDL-I was negatively correlated with plasma triglycerides, VLDL-C, LDL-C, and apolipoprotein (apo) B concentrations. The concentrations of intermediate and small, dense LDL (LDL-II and LDL-III; density, 1.034 to 1.044 and 1.044 to 1.060 g/L, respectively) UK were positively correlated with LDL-C. LDL-III concentrations were also related to plasma cholesterol and apoB concentrations and HL activity. On multivariate analyses, approximately one third of the variability in LDL-I was explained by HL and plasma triglycerides. More than 80% of the variation in LDL-II was accounted for by a model that combined LDL-C and plasma apoB with body mass index and VLDL-TG. Plasma apoB concentrations also featured in multivariate models of LDL-III and together with HL and lipoprotein(a) explained approximately one third of its variability. The activity of HL accounted for the differences in LDL-I between men and women, the reciprocal relation between LDL-I and LDL-III, and the close association of LDL-I with HDL2. These data confirm that HL is a major determinant of LDL subfraction distribution and indicate, through coordinate regulation of LDL-I and HDL2, that these two subfractions should not be considered as independent predictors of coronary risk.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We investigated whether specific lipoprotein abnormalities are present in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension and/or microalbuminuria. Fifteen normotensive normoalbuminuric (H-M-), 32 hypertensive normoalbuminuric (H+M-), and 22 hypertensive microalbuminuric (H+M+) NIDDM patients and 20 sex-, age-, and weight-matched nondiabetic control subjects were studied. Lipoprotein size was measured by nondenaturing polyacrylamide gradient gel electrophoresis; insulin sensitivity was assessed by using a euglycemic hyperinsulinemic clamp and [6,62H]glucose tracer infusion for simultaneous measurement of hepatic glucose output and wholebody glucose utilization. Total plasma and very-low-density lipoprotein cholesterol were higher in H+M+ than in control subjects (5.84±0.98 versus 4.97±0.98 and 0.57±0.54 versus 0.26±0.21 mmol/L, mean±SD,P< .05). Plasma triglycerides were higher in H+M+ than in either control or H–M– subjects (2.17±1.32 versus 1.18±0.67 and 1.30±0.59 mmol/L, respectively;P< .05). The mean low-density lipoprotein diameter was 27.2±0.8 in control, 26.7±0.8 in H-M-, 26.5±0.8 nm in H+M− (P<.05 versus control subjects), and 26.0±0.8 nm in H+M+ subjects (P< .05 versus control subjects). The mean cholesterol level of the large high-density lipoprotein particles was lower in H+M− and H+M+ (0.37 ± 0.14 and 0.36 ± 0.16 mmol/L) than in control and H-M (0.54 ± 0.41 and 0.54 ± 0.27 mmol/L,p<.05) subjects. Whereas hepatic glucose output was less inhibited in all diabetic patients than in control subjects, whole-body glucose disposal was lower in H+M+ (97 ± 13 mg/m2 per minute, mean ± SEM,p<.05) and H+M− (69 ± 12 mg/m2 per minute,p<.05) but not in H-M (277 ± 38 mg/m2 per minute) NIDDM patients than in control subjects (263 ± 45 mg/m2 per minute). Hypertension (without or with microalbuminuria) appears to be associated with small low-density lipoprotein particles and low high-density lipoprotein cholesterol2, while microalbuminuria (with hypertension) is associated with elevated triglycerides in NIDDM patients. Moreover, in NIDDM patients the presence of hypertension with or without microalbuminuria is associated with impaired extrahepatic insulin sensitivity. The atherogenic lipoprotein pattern might partially explain why NIDDM patients with microalbuminuria and hypertension are prone to cardiovascular diseases.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Persons from the Indian subcontinent have elevated coronary heart disease risk. We measured insulin resistance with the insulin suppression test in 22 Asian Indian men and women and an equal number of control subjects of European ancestry matched for age and body mass index. Asian men and women had increased glucose and insulin responses to oral glucose tolerance tests (P< .05 by ANOVA) and had approximately 60% higher steady-state plasma glucose levels during the insulin suppression test (P< .001 by ANOVA), consistent with insulin resistance. In response to mixed meals, Asian women had higher plasma free fatty acids and glycerol concentrations than women of European ancestry (P< .02 by ANOVA), whereas Asian Indian men had similar free fatty acid and glycerol levels compared with men of European ancestry despite higher plasma insulin levels. Thus, results in both sexes were consistent with resistance to insulin suppression of free fatty acid levels in Asian Indians. Asian Indians of both sexes had higher fasting plasma triglyceride (p< .01) and lower high-density lipoprotein cholesterol (p< .01) concentrations than men and women of European ancestry. Resistance to insulin-stimulated glucose uptake and to insulin suppression of free fatty acid levels in Asian Indians is associated with a number of metabolic abnormalities that are demonstrated risk factors for coronary heart disease, including increased glucose, insulin, and triglyceride concentrations and decreased high-density lipoprotein cholesterol concentrations.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Low levels of high-density lipoproteins (HDLs) may constitute an independent risk factor that may be as important as elevated low-density lipoproteins (LDLs) in coronary artery disease (CAD). Concentrations and distributions of lipids, apolipoprotein (apo) B, and apoA-I in the plasma and lipoprotein subfractions of two groups of swine, one with familial hypercholesterolemia (FHC) and the other with diet-induced hypercholesterolemia (DHC), were examined. Normolipidemic (NL) animals served as controls. All pigs carried the Lpb5 apoB mutation, which is known to influence the formation of atherosclerotic lesions. Mean concentrations of serum total cholesterol in NL, DHC, and FHC were 80.0+9.3, 774.3±54.5, and 316.5±36.1 mg/dL, respectively; HDL cholesterol (HDL-C), 33.5±1.9, 137.0±9.9, and 22.3±2.2 mg/dL; triglycerides, 33.0+16.3, 40.3±11.7, and 56.8±7.2 mg/dL; apoB, 35.7±3.1, 142.0±4.8, and 169.3+13.9 mg/dL; and apoA-I, 62.4±9.3, 170.9±6.9, and 42.6±4.8 mg/dL. The distributions of total cholesterol, apoB, and apoA-I in plasma lipoprotein subfractions were also examined. Compared with NL, FHC had fourfold and 4.7-fold increases in total cholesterol and apoB, respectively, distributed in the lower densities (d< 1.043 g/mL), and low HDL-C and apoA-I levels, resulting in a high total cholesterol/HDL-C ratio (14.4:1) and elevated triglyceride levels. DHC was characterized by 10-fold and fourfold increases in total cholesterol and apoB, respectively, resulting in an LDL particle highly enriched in cholesterol, a fourfold increase of HDL-C, an almost threefold increase in apoA-I, and a normal triglyceride level. Thus FHC but not DHC exhibited a marked resemblance to familial combined hyperlipidemia, the most common endogenous dyslipidemia in humans.

ISSN:1049-8834    

出版商:OVID    

年代:1994

数据来源: OVID