Biomedical subjects

E J Schaefer

Publications and source records attributed to E J Schaefer.

At least 199 records · Page 11Linked to original sources

PubMed1993

Diet and exercise and gemfibrozil therapy for the management of dyslipidemia: a CEN study. Clinical Experience Network.

BACKGROUND: Dyslipidemia constitutes a serious health problem that should be diagnosed and treated by the family physician. Little is known about the efficacy of typical dietary therapy for patients with abnormal cholesterol levels. This study was the first large prospective family practice evaluation of the effectiveness of diet-and-exercise therapy followed by a pharmacologic intervention for those patients who remained dyslipidemic. METHODS: Patients who met standard criteria for cardiovascular disease risk based on lipid analysis were enrolled in a typical 6-week physician-directed diet-and-exercise program. Those patients who were still dyslipidemic after that period were started on 12 weeks of pharmacologic treatment with gemfibrozil. RESULTS: Of the 2992 patients screened, 1193 were eligible for participation in the study. The diet-and-exercise program led to a modest change in lipid values (average decrease in total cholesterol of 4.1%). Only 2% of the patients achieved desirable levels of all lipid values. Seven hundred thirty-nine subjects qualified for further therapy and were treated with gemfibrozil. Seventy patients discontinued drug therapy because of adverse effects. Those who completed 12 weeks of pharmacologic therapy had an additional 5.4% reduction in total cholesterol, 3.9% reduction in low-density lipoprotein cholesterol, 30.6% reduction in triglycerides, and a 17.2% increase in high-density lipoprotein cholesterol. CONCLUSIONS: These findings suggest that in a typical clinical setting, a nonpharmacologic intervention of diet and exercise may not produce the desired overall lipid changes in the majority of dyslipidemic patients.

Cholesterol↗

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

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

Change in LDL particle size is associated with change in plasma triglyceride concentration.

Low density lipoprotein (LDL) particle size is inversely associated with plasma triglyceride concentration in cross-sectional analyses. In the present study, changes in the LDL particle size of 227 participants of the Framingham Offspring Study were analyzed longitudinally by nondenaturing gradient gel electrophoresis at two examinations that were separated by 3-4 years. All subjects had triglyceride concentrations < 400 mg/dl at both exams. Using laser scanning densitometry to assess mean LDL particle size, 56% of samples displayed a change in size: 41% had a one-band size change, 13% had a two-band change, and 2% had a three-band change. These changes in size corresponded to a 15% change in pattern type, based on pattern A and B terminology. There was a significant inverse association between change in LDL size and change in triglyceride (p < 0.0001) and glucose (p < 0.004) concentrations, body weight (p < 0.02), and age (p < 0.03). There was also a significant positive association with change in high density lipoprotein (HDL) cholesterol concentration (p < 0.0001). Change in LDL cholesterol concentration, as calculated by use of the Friedewald formula, however, showed no significant association with change in LDL size (p < 0.9). There was also no significant association with change in smoking or blood pressure, but there was a nonsignificant inverse trend associated with alcohol intake (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

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↗

PubMed1992

Plasma docosahexaenoic acid levels in various genetic forms of retinitis pigmentosa.

In 188 patients from separate families with various forms of retinitis pigmentosa (RP) and 91 normal subjects, plasma fatty acids were measured as a percentage of total plasma fatty acids, and their concentrations were determined using capillary-column gas-liquid chromatography. After controlling for the effects of age and gender, those with RP had significantly lower (P less than 0.01) mean plasma percentages and concentrations of the omega-3 fatty acids: 18:3 omega 3 (alpha-linolenic acid), 22:3 omega 3 (13,16,19 docosatriaenoic acid), and 22:6 omega 3 (docosahexaenoic acid, DHA) compared with the group of normal subjects. The mean percentages were reduced 15%, 14%, and 10%, respectively, below the mean percentages in normal subjects. Analysis by genetic type revealed that the X-linked and isolate forms of RP had significantly lower (P less than 0.01) mean percentage values for DHA (18% and 17%, respectively). Dominant and recessive forms of RP had DHA levels close to normal. Mean absolute plasma DHA concentrations in X-linked RP were not significantly different from the concentrations in the control subjects, although these levels were significantly lower in patients with isolate RP. These data identify the possibility that some forms of RP may have alterations in plasma omega-3 fatty acid metabolism resulting in decreased plasma DHA content. These observations await additional confirmation using an analysis of the fatty acid content of specific erythrocyte phospholipid classes.

Adolescent↗

PubMed1992

Measurement of human apolipoprotein B-48 and B-100 kinetics in triglyceride-rich lipoproteins using [5,5,5-2H3]leucine.

A primed-constant infusion of deuterated leucine was used in humans to determine the maximal level of enrichment at plateau of apolipoprotein (apo)B-48 and apoB-100 which are synthesized in the intestine and liver, respectively, and to compare the kinetics of these two proteins under identical conditions. Eight normal subjects (four post-menopausal females and four males) over the age of 40 were studied in the constantly fed state over a 20-h period by providing small hourly feedings of identical composition. [5,5,5-2H3]Leucine (10 mumol/kg body weight followed by 10 mumol/kg body weight per hour) was infused over 15 h intravenously. The enrichment of deuterated leucine in apoB-48 and apoB-100 triglyceride-rich lipoproteins isolated by ultracentrifugation (d less than 1.006 g/ml) was determined during the entire infusion period. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-48 was 3.96 +/- 1.41 tracer/tracee ratio (%) which was 39.7% of the plasma leucine enrichment level. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-100 was 7.23 +/- 1.17 tracer/tracee ratio (%) which was 72.5% of the plasma leucine enrichment level. Mean fractional secretion rates of triglyceride-rich lipoprotein apoB-48 and apoB-100 were 4.39 +/- 2.00 and 5.39 +/- 1.98 pools per day, respectively, with estimated residence times of 5.47 and 4.45 hours, respectively. The data indicate that in the fed state there is about a twofold difference in the plateau enrichment of an intestinally derived protein, as compared to one of hepatic origin, most likely attributable to differences in the enrichment of the intracellular leucine in the two organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Prevalence of risk factors in men with premature coronary artery disease.

The prevalence of modifiable cardiovascular risk factors (systemic hypertension, diabetes mellitus, cigarette smoking, low-density lipoprotein [LDL] cholesterol greater than or equal to 160 mg/dl and high-density lipoprotein [HDL] cholesterol less than 35 mg/dl) was determined in 321 men less than 60 years of age (mean +/- standard deviation 50 +/- 7) with premature coronary artery disease (CAD) documented at coronary angiography. The prevalence of these risk factors was markedly different than in the Framingham Offspring Study population, used here as a comparison group. In the patients with CAD, only 3% had no risk factor (other than male sex), compared with 31% in the Framingham Offspring Study subjects. Most patients with CAD (97%) had greater than or equal to 1 additional risk factor. When the patients with CAD were divided by age groups (40 to 49 years [n = 109], 50 to 59 [n = 191]), no significant differences were observed in the prevalence of risk factors between the young and older patients. The prevalence of systemic hypertension (41 vs 19%, p less than 0.001), diabetes mellitus (12 vs 1.1%, p less than 0.001), cigarette smoking (67 vs 28%, p less than 0.001) and HDL cholesterol less than 35 mg/dl (63 vs 19%, p less than 0.001) was markedly higher in the patients with CAD than in Framingham Offspring Study subjects, whereas the prevalence of LDL cholesterol greater than or equal to 160 mg/dl was not significantly different between patients with CAD and Framingham Offspring Study subjects (26 vs 26%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Prevalence of lipoprotein (a) [Lp(a)] excess in coronary artery disease.

Lipoprotein (a) [Lp(a)] is composed of 1 low-density lipoprotein (LDL) particle, to which 1 molecule of apolipoprotein (a) is covalently linked. Elevated levels of Lp(a) have been associated with coronary artery disease (CAD) and Lp(a) has been shown to be highly heritable. Our purpose was to determine the prevalence of familial Lp(a) excess in patients with CAD. We determined plasma levels of Lp(a) in 180 patients (150 men and 30 women) with angiographically documented CAD before age 60 years, and in 459 control subjects (276 men and 183 women) clinically free of cardiovascular disease. In addition, Lp(a) levels were determined in families of 102 of the CAD probands (87 men and 15 women). No gender differences in Lp(a) levels were observed between men and women (patients or control subjects). Patients with CAD had higher Lp(a) levels than did control subjects (19 +/- 21 vs 13 +/- 15 mg/dl, p less than 0.001). The prevalence of Lp(a) excess (defined as greater than 90th percentile of controls) was 17% in patients with CAD (p less than 0.05). Lp(a) levels were not correlated with cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol or apolipoproteins A-I or B. There was a weak correlation between Lp(a) and triglycerides (r = 0.166, p less than 0.05) in patients and control subjects. Stepwise discriminant analysis revealed that Lp(a) was a risk factor for the presence of CAD in men, independent of smoking, hypertension, diabetes, LDL and HDL cholesterol, or apolipoprotein A-I and B levels. Family studies revealed that Lp(a) levels are strongly genetically determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗

PubMed1991

Plasma apolipoprotein A-I, A-II, B, E and C-III containing particles in men with premature coronary artery disease.

Lipoprotein (Lp) cholesterol and apolipoproteins (apo) A-I and B levels have been shown to be better markers for the presence of coronary artery disease than total cholesterol. In this study, we determined the plasma levels of lipoprotein particles containing apo A-I only (LpA-I), apo A-I and A-II (LpA-I:A-II), apo B and C-III (LpB:C-III) and apo B and E (LpB:E) in 145 patients with coronary artery disease (mean age +/- SD, 51 +/- 7 years) and 135 healthy control men (mean age 49 +/- 11 years). Patients with CAD had lower high density lipoprotein (HDL) cholesterol and apo A-I levels and higher triglycerides and apo had lower high density lipoprotein (HDL) cholesterol and apo A-I levels and higher triglycerides and apo B levels than controls. In patients with CAD, LpA-I (0.341 +/- 0.093 vs. 0.461 +/- 148 g/l) and LpA-I:A-II (0.694 +/- 0.171 vs. 0.899 +/- 0.148 g/l) were lower, whereas LpB:E (0.372 +/- 0.204 vs. 0.235 +/- 0.184 g/l) were higher than in controls (cases vs. controls, all P less than 0.005). No significant differences were observed for LpB:C-III (0.098 +/- 0.057 vs. 0.107 +/- 0.061 g/l, p = 0.235) particles. Discriminant analysis indicates that LpA-II:A-I, LpE:B, LpA-I, and triglycerides best differentiate between cases and controls. Plasma apo C-III (0.027 +/- 0.008 vs. 0.036 +/- 0.020 g/l) and E (0.040 +/- 0.015 vs. 0.055 +/- 0.029 g/l) were lower in the CAD group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1991

The NHLBI Twin Study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a).

Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The intraclass correlation coefficient for apo A-I was significantly greater in MZ twins (0.56) than in DZ twins (0.37, P less than 0.05); however, apo A-I showed an unequal distribution in the two groups, with significantly greater total variance in DZ twins. Therefore the among-component estimate of genetic variance was applied, and the results indicated no significant heritability for apo A-I (P = 0.59). MZ and DZ twins had equal apo B variance. The intraclass correlation coefficient for apo B in MZ twins (0.71) was significantly higher than in DZ twins (0.25) (P less than 0.0001), indicating significant heritability for apo B. Plasma apo A-I levels were significantly correlated with alcohol intake (P less than 0.0001), body mass index (BMI, P less than 0.0001), and physical activity, while apo B levels were significantly correlated only with BMI (P less than 0.05). After plasma apo A-I and apo B concentrations were adjusted for all of these variables and for cigarette smoking, the analysis of variance and intraclass correlation coefficients remained virtually unchanged. The LDL type intraclass correlation coefficient was higher in MZ twins (0.58) than in DZ twins (0.32, P less than 0.005); however, greater total variance for this parameter in DZ twins was observed and after applying the among component estimate of genetic variance, no significant heritability of LDL type was observed. After adjustment for covariate effects the conclusions were not changed. Only 8.4% of MZ twin pairs, as compared with 26.7% of DZ twin pairs, were discordant for elevated lipoprotein(a) on gradient gels (P less than 0.0001). Our data indicate that there is a strong heritability for plasma apo B and lipoprotein(a), with only weak evidence for heritability of LDL type or plasma apo A-I levels within this population sample.

Aged↗

PubMed1991

Influence of placentation on high density lipoproteins in adult males: the NHLBI twin study.

Dizygotic (DZ) World War II veteran twins who participated in the National Heart Lung and Blood Institute (NHLBI) Twin Study have been reported to have greater variance than monozygotic (MZ) twins for plasma high-density lipoprotein cholesterol (HDL-C), cholesterol in the low-density fraction of HDL (HDL2-C) and apolipoprotein A-I, a major protein component of HDL. It was hypothesized that a possible source of this difference in zygosity variance could be prenatal environmental influences related to placental type. Dermatoglyphics were used to provide a retrospective index of placental type in a subset of the NHLBI MZ twins aged 59-70. The MZ twins classified as dichorionic were found to have significantly greater within-pair variability than the monochorionic MZ twins for HDL-C, HDL2-C and Apo A-I. These findings indicate that intrauterine environmental influences on HDL are manifest later in life.

Aged↗

PubMed1991

Food use and health effects of soybean and sunflower oils.

This review provides a scientific assessment of current knowledge of health effects of soybean oil (SBO) and sunflower oil (SFO). SBO and SFO both contain high levels of polyunsaturated fatty acids (PUFA) (60.8 and 69%, respectively), with a PUFA:saturated fat ratio of 4.0 for SBO and 6.4 for SFO. SFO contains 69% C18:2n-6 and less than 0.1% C18:3n-3, while SBO contains 54% C18:2n-6 and 7.2% C18:3n-3. Thus, SFO and SBO each provide adequate amounts of C18:2n-6, but of the two, SBO provides C18:3n-3 with a C18:2n-6:C18:3n-3 ratio of 7.1. Epidemiological evidence has suggested an inverse relationship between the consumption of diets high in vegetable fat and blood pressure, although clinical findings have been inconclusive. Recent dietary guidelines suggest the desirability of decreasing consumption of total and saturated fat and cholesterol, an objective that can be achieved by substituting such oils as SFO and SBO for animal fats. Such changes have consistently resulted in decreased total and low-density-lipoprotein cholesterol, which is thought to be favorable with respect to decreasing risk of cardiovascular disease. Also, decreases in high-density-lipoprotein cholesterol have raised some concern. Use of vegetable oils such as SFO and SBO increases C18:2n-6, decreases C20:4n-6, and slightly elevated C20:5n-3 and C22:6n-3 in platelets, changes that slightly inhibit platelet generation of thromboxane and ex vivo aggregation. Whether chronic use of these oils will effectively block thrombosis at sites of vascular injury, inhibit pathologic platelet vascular interactions associated with atherosclerosis, or reduce the incidence of acute vascular occlusion in the coronary or cerebral circulation is uncertain. Linoleic acid is needed for normal immune response, and essential fatty acid (EFA) deficiency impairs B and T cell-mediated responses. SBO and SFO can provide adequate linoleic acid for maintenance of the immune response. Excess linoleic acid has supported tumor growth in animals, an effect not verified by data from diverse human studies of risk, incidence, or progression of cancers of the breast and colon. Areas yet to be investigated include the differential effects of n-6- and n-3-containing oil on tumor development in humans and whether shorter-chain n-3 PUFA of plant origin such as found in SBO will modulate these actions of linoleic acid, as has been shown for the longer-chain n-3 PUFA of marine oils.(ABSTRACT TRUNCATED AT 400 WORDS)

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