Biomedical subjects

J M Ordovas

Publications and source records attributed to J M Ordovas.

At least 19 recordsLinked to original sources

PubMed1995

Body weight and low-density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet.

OBJECTIVE: To assess the effects of a diet restricted in fat, saturated fat, and cholesterol, under weight-maintenance and ad libitum conditions on body weight and plasma lipid levels in hypercholesterolemic subjects. DESIGN: Dietary intervention study. SETTING AND PARTICIPANTS: Twenty-seven free-living, healthy middle-aged and elderly men (n = 13, age range, 41 to 81 years) and women (n = 14, age range, 52 to 79 years) with moderate hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 3.36 mmol/L [130 mg/dL]) participated in the study. INTERVENTION: Subjects underwent three dietary phases. First, subjects were provided with a diet similar to the average US diet (baseline diet; 35.4% total fat, 13.8% to 14.1% saturated fat, and 30 to 35 mg/1000 kJ [128 to 147 mg/1000 kcal] cholesterol). During the second dietary phase, subjects consumed a low-fat diet (15.1% total fat, 5.0% saturated fat, 17 mg/1000 kJ [73 mg/1000 kcal] cholesterol). During the baseline and low-fat diet phases, which lasted 5 to 6 weeks each, the energy intake was adjusted to keep body weight constant. During the third diet phase (low-fat ad libitum diet) subjects were given the same low-fat diet for 10 to 12 weeks, but could adjust their intake between 66% and 133% of the energy required to maintain body weight. MAIN OUTCOME MEASURES: Body weight and plasma lipid levels. RESULTS: Consumption of the low-fat diet under weight-maintenance conditions had significant lowering effects on plasma total cholesterol (TC), LDL-C, and high-density lipoprotein cholesterol (HDL-C) levels (mean change, -12.5%, -17.1%, and -22.8%, respectively). This diet significantly increased plasma triglyceride levels (+47.3%) and the TC/HDL-C ratio (+14.6%). In contrast, consumption of the low-fat ad libitum diet was accompanied by significant weight loss (3.63 kg), by a mean decrease in LDL-C (124.3%), and by mean triglyceride levels and TC/HDL-C ratio that were not significantly different from values obtained at baseline. CONCLUSIONS: Our results indicate that a low-fat ad libitum diet promotes weight loss and LDL-C lowering without adverse effects on triglycerides or the TC/HDL-C ratio in middle-aged and elderly men and women with moderate hypercholesterolemia.

Aged↗

PubMed1995

Lovastatin inhibits diet induced atherosclerosis in F1B golden Syrian hamsters.

3-Hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase inhibitors are the drugs most commonly prescribed in the US to lower blood cholesterol. Previous studies have shown their efficacy in reducing plasma low density lipoprotein (LDL) cholesterol. However, little is known about their effects on preventing diet induced atherosclerosis. We have investigated the changes in lipoprotein profiles and extent of atherogenesis in hamsters (F1B strain) consuming an atherogenic diet with and without lovastatin. Thirty-six animals were randomized into 3 groups of 12 animals each, with similar plasma cholesterol levels. One group of animals received a basal chow diet, and the other two groups a basal diet plus 10% (w/w) coconut oil and 0.05% cholesterol. After 2.5 weeks, one of the groups received the latter diet supplemented with lovastatin (25 mg/kg/day). A second study was carried out in which animals received the same diets, but lovastatin was given during the 10 week period at a dose of 12.5 mg/kg/day. At the end of the experimental period, animals were sacrificed and lipoprotein cholesterol, liver enzymes, and aortic foam cell development were determined. Animals fed the high fat diet plus lovastatin had significantly lower levels of non-high density lipoprotein (HDL) cholesterol than those fed the unsupplemented high fat diet. No differences were observed in mean levels of this parameter between animals fed the low fat diet and those receiving lovastatin. The amount of aortic lipid staining was significantly less in the lovastatin and low fat groups when compared to the unsupplemented high fat groups. These results indicate that lovastatin can prevent diet induced aortic lipid deposition in this animal model.

Analysis of Variance↗

PubMed1995

Effect of apolipoprotein E and A-IV phenotypes on the low density lipoprotein response to HMG CoA reductase inhibitor therapy.

Our purpose was to assess the effect of apolipoprotein (apo) E and apo A-IV isoform variation on low density lipoprotein (LDL) cholesterol lowering response to the HMG CoA reductase inhibitor, pravastatin. Plasma samples were obtained from participants (apo E, n = 97; apo A-IV, n = 144) in the PLAC-I (Pravastatin Limitation of Atherosclerosis in Coronary Arteries Study-1). The mean LDL cholesterol reduction in these subjects who were randomized to pravastatin 40 mg/day was 28%. Subjects with the APOE*2 allele (n = 12) had significantly (P = 0.04) greater reductions at 36% than subjects homozygous for the APOE*3 allele (n = 66, 27%) or those with the APOE*4 allele (n = 19, 26%). No significant effect of apo A-IV phenotype on LDL cholesterol lowering in response to pravastatin was noted. A meta-analysis utilizing published data from 4 previously published studies as well as our own data with a total sample size of 625 subjects was carried out. This analysis indicates that the presence of the APOE*2 allele was associated with a significantly greater (P < 0.05) LDL-cholesterol lowering response at 37% than those subjects homozygous for the APOE*3 allele at 35%, while those with the APOE*4 allele had a significantly lower response (P < 0.05), at 33%. These data are consistent with the concept that apo E phenotype modulates the LDL cholesterol lowering response observed with the use of HMG CoA reductase inhibitors.

Alleles↗

PubMed1995

Diets enriched in unsaturated fatty acids enhance apolipoprotein A-I catabolism but do not affect either its production or hepatic mRNA abundance in cynomolgus monkeys.

To determine the mechanisms whereby dietary fatty acids influence high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations, ten cynomolgus monkeys were fed each of three experimental diets enriched in saturated (SAT), monounsaturated (MONO), or polyunsaturated (POLY) fatty acids in a crossover design consisting of three 13-week periods, with each animal serving as its own control. Each diet contained 30% of energy as fat with 0.22 mg cholesterol/kcal and differed solely by the isocaloric substitution of fatty acids as 18% of total energy calories. The replacement of dietary saturated fatty acids with either monounsaturated or polyunsaturated fatty acids, respectively, resulted in significant reductions of plasma total cholesterol (-17%; -30%), HDL cholesterol (-32%; -41%), and apo A-I (-37%; -44%) concentrations, while no significant differences were noted in plasma lipid or apo A-I concentrations when the MONO and POLY phases were compared. Although the MONO and POLY diets were similar in their effects on plasma lipids and apolipoproteins, the HDL of monkeys fed the POLY diet, as compared with either the SAT or the MONO diets, contained more cholesteryl ester and phospholipid but less total protein, resulting in a significantly lower total lipid to protein constituent ratio. Metabolic experiments revealed that the significantly lower plasma apo A-I concentrations observed during both the MONO and POLY phases relative to SAT were directly attributable to enhanced HDL apo A-I catabolism. Conversely, neither HDL apo A-I production rates nor hepatic apo A-I mRNA concentrations were significantly affected by dietary fatty acid perturbation in this study. Taken together, these data indicate that fractional catabolic rate is the predominant mechanism by which dietary fatty acids differentially modulate circulating concentrations of HDL apo A-I in this species when all other dietary variables are held constant.

Animals↗

PubMed1995

Gender differences in the development of hyperlipemia and atherosclerosis in hybrid hamsters.

In response to a diet enriched in saturated fat and cholesterol (CH), male Syrian hamsters develop hyperlipemia and changes of early atherosclerosis. However, it has not been determined if female hamsters are equally susceptible to an atherogenic diet. Male and female hamsters of the F1B hybrid strain (Bio Breeders, Fitchburg, MA) were fed either a chow diet or this diet (HiFat) with added saturated fat (10% coconut oil) and CH (0.05%) for up to 12 weeks. Female hamsters ate significantly more than males, and with the HiFat diet gained threefold more weight than males. However, with the HiFat diet, serum triglycerides (TGs) and CH were markedly increased only in male hamsters. Furthermore, only in males was there a significant increase in stainable fat in the aorta that corresponded to an increase in subintimal foam cells. In freely feeding males, the largest percentage increase in serum CH was in the TG-rich fraction of lipoproteins. After females were castrated, serum TG and CH levels increased to the same extent as in males. These studies demonstrate a profound gender difference in response to an atherogenic diet in these hamsters that has parallels to the lipid patterns of humans and their susceptibility to atherosclerosis.

Animals↗

PubMed1995

Lipoprotein concentrations in normolipidemic males consuming oleic acid-rich diets from two different sources: olive oil and oleic acid-rich sunflower oil.

The effects on plasma lipid concentrations of two oleic acid-rich diets, prepared with two different plant oils--olive oil and sunflower oil high in monounsaturated fatty acids (MUFAs)-- were compared with a National Cholesterol Education Program (NCEP) I diet. Twenty-one healthy, normolipidemic, young males consumed an NCEP-I diet (30% of energy as fat) during a 25-d period. Subjects were then assigned to two 4-wk study periods, according to a randomized, crossover design. Group one was placed on an olive oil-enriched diet (40% fat, 22% MUFAs), followed by a 4-wk period of a sunflower oil-enriched diet (40% fat, 22% MUFAs). In group two, the order of the diets was reversed. Both MUFA dietary periods resulted in an increase in high-density-lipoprotein (HDL) cholesterol (7% for the olive oil diet and 4% for the sunflower oil diet) and in apolipoprotein (apo) A-I (9% for both) compared with the NCEP-I diet. Low-density-lipoprotein (LDL) cholesterol and apo B concentrations (x +/- SEM) were lower (P < 0.05) during the sunflower oil diet (2.40 +/- 0.11 mmol/L, 0.85 +/- 0.04 mg/L) than during the olive oil diet (2.64 +/- 0.15 mmol/L, 0.93 +/- 0.05 mg/L). No significant differences were observed in these variables between the sunflower oil and NCEP-I (2.48 +/- 0.13 mmol/L, 0.89 +/- 0.04 mg/L) diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Efficacy of a National Cholesterol Education Program Step 2 diet in normolipidemic and hypercholesterolemic middle-aged and elderly men and women.

We tested the effects of a National Cholesterol Education Program (NCEP) Step 2 diet (30% of calories or less as total fat, less than 7% saturated fat, and less than 200 mg cholesterol per day) on plasma lipid levels in normocholesterolemic and hypercholesterolemic middle-aged and elderly men and women. Thirty-two subjects were studied. Eight normolipidemic subjects (6 men and 2 women, mean age 56 +/- 13 years) with LDL cholesterol levels of less than 4.14 mmol/L (160 mg/dL) were given a baseline diet similar in composition to the diet currently consumed in the United States (35% of calories as total fat and 14% as saturated fat, with 147 mg cholesterol per 1000 kcal) for 6 weeks. Subjects were then placed on an NCEP Step 2 diet (26% total fat, 4% saturated fat, 45 mg cholesterol per 1000 kcal) for 24 weeks. In addition, 24 subjects (12 men and 12 women, mean age 62 +/- 12 years) with moderate hypercholesterolemia (LDL cholesterol levels of 4.14 mmol/L or above) were given a baseline diet for 6 weeks and then the NCEP Step 2 diet for 6 weeks. Energy intakes were adjusted to keep body weight constant throughout the study. In both normolipidemic and hypercholesterolemic subjects, consumption of the NCEP Step 2 diet was associated with significant changes in levels of total cholesterol (-20% and -16%, respectively), LDL cholesterol (-21% and -18%, respectively), and HDL cholesterol (-16% and -15%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease.

The prevalence of abnormalities of lipoprotein cholesterol and apolipoproteins A-I and B and lipoprotein (a) [Lp(a)] was determined in 321 men (mean age 50 +/- 7 years) with angiographically documented coronary artery disease and compared with that in 901 control subjects from the Framingham Offspring Study (mean age 49 +/- 6 years) who were clinically free of coronary artery disease. After correction for sampling in hospital, beta-adrenergic medication use and effects of diet, patients had significantly higher cholesterol levels (224 +/- 53 vs. 214 +/- 36 mg/dl), triglycerides (189 +/- 95 vs. 141 +/- 104 mg/dl), low density lipoprotein (LDL) cholesterol (156 +/- 51 vs. 138 +/- 33 mg/dl), apolipoprotein B (131 +/- 37 vs. 108 +/- 33 mg/dl) and Lp(a) levels (19.9 +/- 19 vs. 14.9 +/- 17.5 mg/dl). They also had significantly lower high density lipoprotein (HDL) cholesterol (36 +/- 11 vs. 45 +/- 12 mg/dl) and apolipoprotein A-I levels (114 +/- 26 vs. 136 +/- 32 mg/dl) (all p less than 0.005). On the basis of Lipid Research Clinic 90th percentile values for triglycerides and LDL cholesterol and 10th percentile values for HDL cholesterol, the most frequent dyslipidemias were low HDL cholesterol alone (19.3% vs. 4.4%), elevated LDL cholesterol (12.1% vs. 9%), hypertriglyceridemia with low HDL cholesterol (9.7% vs. 4.2%), hypertriglyceridemia and elevated LDL cholesterol with low HDL cholesterol (3.4% vs. 0.2%) and Lp(a) excess (15.8% vs. 10%) in patients versus control subjects, respectively (p less than 0.05). Stepwise discriminant analysis indicates that smoking, hypertension, decreased apolipoprotein A-I, increased apolipoprotein B, increased Lp(a) and diabetes are all significant (p less than 0.05) factors in descending order of importance in distinguishing patients with coronary artery disease from normal control subjects. Not applying a correction for beta-adrenergic blocking agents, sampling bias and diet effects leads to a serious underestimation of the prevalence of LDL abnormalities and an overestimation of HDL abnormalities in patients with coronary artery disease. However, 35% of patients had a total cholesterol level less than 200 mg/dl after correction; of those patients, 73% had an HDL cholesterol level less than 35 mg/dl.

Apolipoproteins↗

PubMed1992

Effect of cyclosporin on plasma lipoproteins in bone marrow transplantation patients.

The effects of cyclosporin and prednisone on plasma lipid and lipoprotein levels were studied in 20 allogeneic bone-marrow transplantation patients receiving cyclosporin plus prednisone therapy, and in 14 allogeneic patients treated only with cyclosporin during 100 days. Eighteen autologous bone-marrow patients not requiring cyclosporin were used as a control group. Patients were studied 5 days prior to transplantation, and on days 30, 60, and 100 after transplantation. To determine the reversibility of the changes, lipid parameters were analyzed 30 days after completion of the treatment. Nutritional supplementation, conditioning regimens, and concomitant medications were not significantly different between groups. Furthermore, no significant differences in age, weight, lipid, or lipoprotein levels were found at baseline. Our results indicate that cyclosporin therapy induces a reversible increase of plasma cholesterol, LDL-cholesterol, triglycerides, VLDL-triglycerides, and apolipoprotein B and a decrease of HDL-cholesterol, HDL2-cholesterol, and apolipoprotein A-I. The addition of prednisone to cyclosporin therapy induces a higher increase in plasma cholesterol mainly due to an increase in HDL-cholesterol. Total cholesterol/HDL-cholesterol ratio increased significantly in patients treated only with cyclosporin. No differences were found in this ratio in patients treated with prednisone compared to those submitted to autologous bone-marrow transplantation. Lipid changes observed in this study were reversible 30 days after cessation of cyclosporin treatment.

Adult↗

PubMed1992

The MspI restriction fragment length polymorphism 3' to the apolipoprotein A-II gene: relationships with lipids, apolipoproteins, and premature coronary artery disease.

In previous studies, a restriction fragment length polymorphism (RFLP) has been identified using MspI restriction endonuclease in the 3' region of the apo A-II gene. The rare variant site for this MspI (M2) has been reported to be associated with higher levels of HDL cholesterol and apo A-II. We have studied the frequency and lipid associations of this RFLP in a population of 168 coronary artery disease (CAD) male and female patients, who had more than 50% narrowing of one or more arteries prior to age 60 years, as well as 255 aged-matched males and females from the Framingham Offspring Study. We also studied 31 kindreds in which the proband had premature CAD. The frequency of the M2 allele was higher in CAD cases (0.20) than in the controls (0.13) (P less than 0.05). In general, those subjects carrying the M2 allele had lower HDL cholesterol and apo A-I plasma levels; however, this difference was only significant (P less than 0.02 and 0.002, respectively) in females with CAD. No cosegregation of the M2 allele with hypoalphalipoproteinemia was found in 31 kindreds studied. However, in both generations there was a trend for those subjects carrying the M2 allele to have lower HDL cholesterol levels than those carrying the M1 allele. Sequence analysis of the apo A-II gene of subjects homozygous for either the M1 (n = 1) or the M2 allele (n = 2) revealed that this RFLP is due to a T----C single base mutation 528 bp 3' to the apo A-II gene. In the subjects homozygous for the M2 allele no other mutations were found within the coding region of the apo A-II gene that could result in changes in the primary sequence of the protein. These data indicate that the MspI RFLP 3' to the apo A-II gene is somewhat more frequent in the CAD group. However, there was no significant association between this RFLP and any of the parameters examined. In conclusion, this DNA marker lacks the specificity to be clinically useful for CAD risk assessment in the population studied.

Adult↗

PubMed1992

Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women.

The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, total cholesterol, very-low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-I and B levels and LDL particle size were assessed in 20 postmenopausal women with a previous hysterectomy and various forms of dyslipidemia (LDL cholesterol > or = 4.14 mmol/L [160 mg/dL] and/or HDL cholesterol < or = 1.03 mmol/L [40 mg/dL]). All subjects were studied while on a standard cholesterol-lowering diet, and were sampled in the fasting state before beginning estrogen therapy and after a mean of 13 weeks of estrogen therapy. Lipids were measured by standardized enzymatic techniques, apos were measured by enzyme-linked immunoassays, and LDL particle size was measured by gradient gel electrophoresis. Mean values for plasma lipid parameters (mmol/L) at baseline and during estrogen replacement were as follows: triglyceride, 2.11 and 2.75 (30% increase); total cholesterol, 7.45 and 6.52 (13% decrease); VLDL cholesterol, 1.09 and 1.22 (12% increase); LDL cholesterol, 5.09 and 3.70 (27% decrease); and HDL cholesterol, 1.27 and 1.58 (24% increase). Mean values for apo A-I were 163 and 254 mg/dL (56% increase), and for apo B they were 170 and 148 mg/dL (13% decrease). The LDL particle score was 4.09 and 4.52 (11% smaller). Changes in all parameters were statistically significant (P = .05) except for VLDL cholesterol. These data indicate that estrogen replacement is effective in decreasing LDL cholesterol and apo B concentrations and increasing HDL cholesterol and apo A-I concentrations in dyslipidemic postmenopausal women, but it should not be used in patients with baseline fasting triglyceride levels higher than 2.82 mmol/L (250 mg/dL) unless it is accompanied by a progestin. Our data indicate that this form of estrogen replacement could lower the risk of coronary artery disease (CAD) by more than 50% in these women, based on favorable alterations in plasma lipoproteins.

Aged↗

PubMed1992

Effect of dietary monounsaturated fatty acids on plasma lipoproteins and apolipoproteins in women.

To determine the effects of dietary fat saturation on plasma lipoproteins, we studied 21 free-living normolipidemic women (13 pre- and 8 postmenopausal) on three consecutive diet periods. During the first 4 wk they consumed a saturated diet rich in palm oil and butter [19% saturated fatty acids (S), 14% monounsaturated fatty acids (M), and 3.5% polyunsaturated fatty acids (P)], followed by 6 wk of a monounsaturated diet rich in olive oil (11% S, 22% M, and 3.6% P), and 6 wk of a polyunsaturated diet rich in sunflower oil (10.7% S, 12.5% M, and 12.8% P). Compared with the diet rich in saturated fatty acids, both diets rich in unsaturated fatty acids had similar lowering effects on total and low-density-lipoprotein cholesterol. High-density lipoprotein cholesterol and apolipoprotein A-I were higher in the monounsaturated-rich period than in the polyunsaturated-rich (10.5% and 12.7% respectively, P less than 0.001) and the saturated-rich period (5.3%, and 7.9%, respectively, P less than 0.05). These effects were independent of menopause status. Our data show that at this level of fat intake (36% as calories), a monounsaturated-rich diet results in a less atherogenic lipid profile than either polyunsaturated- or saturated-rich diets.

Adult↗

PubMed1992

LDL particle size distribution. Results from the Framingham Offspring Study.

Using 2-16% gradient gel electrophoresis, we examined low density lipoprotein (LDL) particle size in relation to plasma lipoproteins in 1,168 women and 1,172 men from the Framingham Offspring Study. In addition, we studied the effect of dietary intake on LDL size in a subset of the population. Seven LDL size peaks were identified, with the largest, LDL 1, being found in the density range 1.019-1.033 g/ml; LDL 2 and LDL 3 in d = 1.033-1.038 g/ml; LDL 4 and LDL5 in d = 1.038-1.050 g/ml; and the smallest, LDL 6 and 7, in d = 1.050-1.063 g/ml. Seventy-seven percent of the population had one major and at least one minor LDL peak. Secondary LDL peaks accounted for 23% of the total LDL relative area, based on laser scanning densitometry. LDL size distribution was skewed toward larger LDL particles in women (prevalence of LDL 1, 30% and of LDL 2, 31%), whereas men exhibited a more symmetric distribution (prevalence of LDL 3, 42%). The prevalence of small (< 255 A), dense (d > 1.038 g/ml) LDL particles 4-7 was 33% in men, 5% in premenopausal women, and 14% in postmenopausal women. In agreement with previous reports, small, dense LDL particles were significantly (p < 0.0001) associated with increased triglyceride and apolipoprotein (apo) B levels and decreased HDL cholesterol and apo A-I levels. In addition, we found a significant (p < 0.0001) association between LDL cholesterol and LDL size. The highest LDL cholesterol levels were found among women with LDL 4 (148 mg/dl) and men with LDL 3-5 (138 mg/dl). In addition, the presence of LDL 3 or 4 as secondary peaks was significantly associated with higher LDL cholesterol levels, while smaller secondary LDL peaks were associated with higher triglyceride levels. We also found that compared with subjects with optimal LDL cholesterol levels (< 130 mg/dl), individuals with high-risk LDL cholesterol levels (> or = 160 mg/dl) had 1) a higher prevalence of LDL 3 and 4 (women only) and a lower prevalence of LDL 1 and 2 (women only) and 2) 11% higher LDL cholesterol to apo B ratios, even when matched for LDL particle size. Furthermore, low saturated fat and cholesterol intakes were significantly associated (p < 0.01) with smaller LDL particles. Therefore, the identification of small, dense LDL particles per se may not be a good indicator of coronary artery disease risk in population studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Apolipoproteins↗

PubMed1992

Low density lipoprotein particle size and coronary artery disease.

Decreased plasma low density lipoprotein (LDL) particle size has been associated with premature coronary artery disease (CAD). We examined LDL particle size by 2-16% gradient gel electrophoresis in 275 men with CAD (greater than 75% cross-sectional-area stenosis) and 822 controls. Seven major LDL size bands (with LDL-1 [d = 1.025-1.033 g/ml] being the largest and LDL-7 [d = 1.050-1.063 g/ml, the smallest]) were identified. Because most subjects had two or more adjacent LDL bands, an LDL score was calculated for each subject, with the relative area in each band taken into consideration. Four major LDL particle size groups were classified in the present studies: large LDL, intermediate LDL, small LDL, and very small LDL. The use of beta-blockers was significantly associated with smaller LDL particles. After adjusting for use of this medication, small LDL particles were still more prevalent in CAD patients (39%) compared with controls (27%). The prevalence of large LDL particles was lower in CAD patients (3%) than in controls (24%). Intermediate LDL particles were the most prevalent in both groups, 49% in CAD patients and 46% in controls. The difference in LDL particle size between CAD patients and controls was not independent but was highly associated (p less than 0.0001) with elevated triglyceride levels and decreased high density lipoprotein (HDL) cholesterol levels. Significantly higher LDL cholesterol levels were found in subjects with intermediate and small LDL particles than in those with large or very small LDL particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Prevalence of cardiovascular risk factors in rural and urban Costa Rica.

BACKGROUND: Coronary artery disease (CAD) is becoming more prevalent in developing countries, particularly in the urban areas, in contrast to the CAD mortality trends observed in some industrialized nations. METHODS AND RESULTS: We determined the prevalence of cardiovascular risk factors (hypertension, diabetes, smoking, obesity, total cholesterol greater than or equal to 240 mg/dl and greater than or equal to 200 less than or equal to 239 mg/dl, low density lipoprotein (LDL) cholesterol greater than or equal to 160 mg/dl and greater than 130 less than or equal to 159 mg/dl, and high density lipoprotein (HDL) cholesterol less than 35 mg/dl) in 222 men and 243 women from rural and urban areas of Puriscal, Costa Rica, using the American Cholesterol Education Program guidelines. Urban Puriscal men had a significantly (p less than 0.05) higher prevalence of borderline high-risk total cholesterol (26% versus 14%), borderline high-risk LDL cholesterol (21% versus 11%), smoking (32% versus 13%), and higher prevalence of low HDL cholesterol (34% versus 24%), hypertension (16% versus 13%), diabetes (4.5% versus 2.7%), obesity (21% versus 14%), and saturated fat intake greater than 15% of calories (14% versus 7%) than rural men from Puriscal. No significant differences between rural and urban women were found for any of the cardiovascular risk factors. Urban Puriscal residents were also more sedentary than rural Puriscal residents. CONCLUSIONS: These data indicate that modifiable risk factors are more prevalent in urban than in rural Puriscal, Costa Rica, particularly in men.

Adult↗

PubMed1992

Familial lipoprotein disorders in patients with premature coronary artery disease.

BACKGROUND: Genetic lipoprotein disorders have been associated with premature coronary artery disease (CAD). METHODS AND RESULTS: The prevalence of such disorders was determined in 102 kindreds (n = 603 subjects) in whom the proband had significant CAD documented by angiography before the age of 60 years. Fasting plasma cholesterol, triglyceride, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, and lipoprotein (a) [Lp(a)] values above the 90th percentile and high density lipoprotein (HDL) cholesterol and apo A-I below the 10th percentile of age- and sex-specific norms were defined as abnormal. An abnormality was noted in 73.5% of probands compared with 38.2% in age-matched controls (p less than 0.001), with a low HDL cholesterol level (hypoalphalipoproteinemia) being the most common abnormality (39.2% of cases). In these kindreds, 54% had a defined phenotypic familial lipoprotein or apolipoprotein disorder. The following frequencies were observed: Lp(a) excess, 18.6% (includes 12.7% with no other dyslipidemias); hypertriglyceridemia with hypoalphalipoproteinemia, 14.7%; combined hyperlipidemia, 13.7% (11.7% with and 2.0% without hypoalphalipoproteinemia); hyperapobetalipoproteinemia (elevated apo B only), 5%; hypoalphalipoproteinemia, 4%; hypercholesterolemia (elevated LDL only), 3%; hypertriglyceridemia, 1%; decreased apo A-I only, 1%. Overall, 54% of the probands had a familial dyslipidemia; unclassifiable lipid disorders (spouse also affected) were found in 3%. No identifiable familial dyslipidemia was noted in 43% of kindreds of those; nearly half (45%) had a sporadic lipid disorder. Parent-offspring and proband-spouse correlations for these biochemical variables revealed that lipoprotein and apolipoprotein levels are in part genetically determined, with Lp(a) showing the highest degree of parent-offspring correlation. CONCLUSIONS: Our data indicate that more than half of patients with premature CAD have a familial lipoprotein disorder, with Lp(a) excess, hypertriglyceridemia with hypoalphalipoproteinemia, and combined hyperlipidemia with hypoalphalipoproteinemia being the most common abnormalities.

Coronary Disease↗

PubMed1992

Effects of dietary fats and cholesterol on liver lipid content and hepatic apolipoprotein A-I, B, and E and LDL receptor mRNA levels in cebus monkeys.

The effects of the long-term administration of the dietary fats coconut oil and corn oil at 31% of calories with or without 0.1% (wt/wt) dietary cholesterol on plasma lipoproteins, apolipoproteins (apo), hepatic lipid content, and hepatic apoA-I, apoB, apoE, and low density lipoprotein (LDL) receptor mRNA abundance were examined in 27 cebus monkeys. Relative to the corn oil-fed animals, no significant differences were noted in any of the parameters of the corn oil plus cholesterol-fed group. In animals fed coconut oil without cholesterol, significantly higher (P less than 0.05) plasma total cholesterol (145%), very low density lipoprotein (VLDL) + LDL (201%) and high density lipoprotein (HDL) (123%) cholesterol, apoA-I (103%), apoB (61%), and liver cholesteryl ester (263%) and triglyceride (325%) levels were noted, with no significant differences in mRNA levels relative to the corn oil only group. In animals fed coconut oil plus cholesterol, all plasma parameters were significantly higher (P less than 0.05), as were hepatic triglyceride (563%) and liver apoA-I (123%) and apoB (87%) mRNA levels relative to the corn oil only group, while hepatic LDL receptor mRNA (-29%) levels were significantly lower (P less than 0.05). Correlation coefficient analyses performed on pooled data demonstrated that liver triglyceride content was positively associated (P less than 0.05) with liver apoA-I and apoB mRNA levels and negatively associated (P less than 0.01) with hepatic LDL receptor mRNA levels. Liver free and esterified cholesterol levels were positively correlated (P less than 0.05) with liver apoE mRNA levels and negatively correlated (P less than 0.025) with liver LDL receptor mRNA levels. Interestingly, while a significant correlation (P less than 0.01) was noted between hepatic apoA-I mRNA abundance and plasma apoA-I levels, no such relationship was observed between liver apoB mRNA and plasma apoB levels, suggesting that the hepatic mRNA of apoA-I, but not that of apoB, is a major determinant of the circulating levels of the respective apolipoprotein. Our data indicate that a diet high in saturated fat and cholesterol may increase the accumulation of triglyceride and cholesterol in the liver, each resulting in the suppression of hepatic LDL receptor mRNA levels. We hypothesize that such elevations in hepatic lipid content differentially alter hepatic apoprotein mRNA levels, with triglyceride increasing hepatic mRNA concentrations for apoA-I and B and cholesterol elevating hepatic apoE mRNA abundance.

Animals↗

PubMed1991

Hepatic expression of apolipoprotein A-I gene in rats is upregulated by monounsaturated fatty acid diet.

The effect of the degree of dietary fat saturation on the hepatic expression of apolipoprotein A-I mRNA was studied in male rats. Animals were maintained for two months on a high fat diet (40% w/w) containing 0.1% cholesterol. Two groups of control animals received either chow diet or chow plus 0.1% cholesterol, while experimental groups received their fat supplement as coconut, corn or olive oil respectively. Dietary cholesterol did not affect apolipoprotein A-I mRNA levels as compared to control animals. Corn oil fed animals had significantly higher levels of hepatic apolipoprotein A-I mRNA than those receiving cholesterol, or coconut oil plus cholesterol. Olive oil fed animals had significantly higher levels of hepatic apolipoprotein A-I mRNA when compared to all other dietary groups. Our data indicate that monounsaturated fatty acids supplied as olive oil play a major role in regulating the hepatic expression of apolipoprotein A-I in male rats.

Animals↗