Blood lipid distributions in older persons. Prevalence and correlates of hyperlipidemia.

Wallace RB, Colsher PL.

Department of Preventive Medicine and Environmental Health, University of Iowa, Iowa City 52242.

Distributions of blood total cholesterol, triglyceride, low-density-lipoprotein (LDL) cholesterol, and high-density-lipoprotein (HDL) cholesterol levels are presented for a geographically defined cohort of rural elderly Iowans, 71 to 102 years old. Cross-sectionally, women had higher levels of total and LDL cholesterol than men did, levels that declined with increasing age. Mean HDL cholesterol levels were also higher in women than in men, but remained relatively constant across the age range. Age- and sex-specific total, LDL, and HDL cholesterol levels were lower among participants residing in long-term-care facilities. HDL but not total cholesterol levels were lower in cigarette smokers and those with chronic illnesses, physical dependence, and poorer performance on physical function tests, and higher among those consuming alcohol. If subjected to the screening guidelines of the National Cholesterol Education Program, a majority of this population, having total cholesterol levels of 5.2 mmol/L (200 mg/dL) or higher, would require further evaluation for possible hyperlipidemia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1342257&dopt=Abstract cholesterol




A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons.

Rainwater DL, Blangero J, Hixson JE, Birnbaum S, Mott GE, VandeBerg JL.

Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78228-0147.

A polymorphic Pvu II site was mapped to intron 5 of LCAT, the gene encoding baboon lecithin: cholesterol acyltransferase (LCAT). In a study of 83 baboons, heterozygous baboons (Pv1/Pv2) had significantly higher LCAT enzyme activity levels than did baboons homozygous for the more common allele (Pv1/Pv1). LCAT genotype explained 6% of the total variation in LCAT enzyme activity. To test for allelic effects on cholesterol metabolism, we compared serum concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I). We also compared distributions of cholesterol and apo A-I among three HDL size classes (HDL1, HDL2, and HDL3). All measurements were obtained for each baboon after long-term feeding of a basal diet low in cholesterol and fat and again after 7 weeks on an atherogenic diet. Heterozygous baboons had significantly lower serum levels of total cholesterol than did homozygotes. In addition, we detected significant effects of LCAT genotype on size distributions of HDL cholesterol and apo A-I on both diets but did not detect any genotype-by-diet interaction. Heterozygotes had increased amounts of cholesterol and apo A-I in HDL3 particles and lower amounts of cholesterol and apo A-I in the larger HDL size classes by comparison with homozygotes. Overall, the LCAT polymorphism explained a significant proportion of total variation in cholesterol (4-10%) and apo A-I (13%) distributions on both diets. Thus, the results indicate that the LCAT polymorphism is associated with significant differences in LCAT enzyme activity and with alterations in HDL compositions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1350465&dopt=Abstract cholesterol




Time-dependent change in the effect of probucol in subjects with elevated cholesterol.

Fujimura A, Ohashi K, Ebihara A.

Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.

A time-dependent change in the cholesterol-lowering effect of probucol has been evaluated in 20 subjects with elevated cholesterol. Probucol 500 mg was given once daily at 07.00 h (day trial) or 19.00 h (night trial) for 3 months according to a crossover design. Fasting blood samples were obtained during the control period and at the end of each treatment period. Serum concentrations of total and HDL-cholesterol were significantly decreased by both the treatments with probucol [total cholesterol (mmol.l-1): control 6.58; day trial 5.41; night trial 5.10; HDL-cholesterol (mmol.l-1): control 1.35; day trial 1.06; night trial 0.96]. These parameters were significantly lower in the night trial than in the day trial. The data indicate that the cholesterol-lowering effect of probucol varies with its time of administration in subjects with elevated cholesterol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1425896&dopt=Abstract cholesterol




Altered pattern of lipid metabolism in patients with lung cancer.

Dessi S, Batetta B, Pulisci D, Spano O, Cherchi R, Lanfranco G, Tessitore L, Costelli P, Baccino FM, Anchisi C, et al.

Istituto Patologia Sperimentale, Cagliari, Italia.

Cholesterol distribution in tumoral tissues and lipid composition in the plasma compartment were determined in patients affected by different histologic types of lung cancer. The results showed that tumoral lung tissues contained 2-fold more total cholesterol and 3.5-fold more esterified cholesterol than normal lung tissues. In the patients the alterations in intracellular cholesterol were also associated with peculiar changes in cholesterol distribution in the plasma compartment. Serum high-density lipoprotein (HDL) cholesterol levels were markedly lower in than in controls. No significant changes in other lipid parameters were observed in these patients. We suggest that the reduced levels of serum HDL cholesterol observed in patients with lung tumors may be a consequence of the disease, probably mediated by the greater utilization of cholesterol for new membrane biogenesis and by the accumulation of esterified cholesterol in tumoral tissues.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1465281&dopt=Abstract cholesterol




Pathophysiology of elevated ascites fluid cholesterol in malignant ascites. Increased ascites to serum relation of proteins and lipoproteins in patients with peritoneal carcinomatosis as compared to patients with cirrhosis of the liver.

Jungst D, Xie Y, Gerbes AL.

Department of Medicine II, Ludwig-Maximilians-University of Munich, Federal Republic of Germany.

The existence of marked elevations of ascitic fluid cholesterol has been observed in patients with peritoneal carcinomatosis compared to patients with cirrhosis and has been found useful in differential diagnosis. This finding could be caused by an enhanced movement of plasma lipoproteins into the peritoneal cavity. To test this hypothesis we determined the fasting concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, apolipoprotein-A1 (apo-A1) and apolipoprotein-B (apo-B) in serum and ascites of 17 patients with cirrhosis and 16 patients with peritoneal carcinomatosis. The movement of proteins from plasma to ascites was calculated from the ascites/serum concentration ratios of six different sized proteins with a molecular mass ranging from 54 kDa to 971 kDa. Mean values (mg/dl) for total cholesterol (92.6 vs. 21.0), HDL-cholesterol (15.6 vs. 1.8), LDL-cholesterol (63.4 vs. 16.1), apo-A1 (50.2 vs. 13.6) and apo-B (41.2 vs. 12.9) in ascites were significantly higher in peritoneal carcinomatosis than in cirrhosis. These differences could only partially be explained by the higher serum concentrations of these parameters in peritoneal carcinomatosis, but were mainly due to a lower selectivity for the movement of plasma proteins and lipoproteins into ascites (mean ascites/serum (A/S) ratio: 0.30-0.77) in peritoneal carcinomatosis as compared to cirrhosis (mean ascites/serum ratio: 0.11-0.21). In both groups about 85% of the total cholesterol in serum and ascites consisted of HDL- and LDL-cholesterol. These findings support the hypothesis that elevations in ascitic cholesterol in peritoneal carcinomatosis compared to cirrhosis are mainly caused by the increased movement of plasma HDL and LDL into the peritoneal cavity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1500688&dopt=Abstract cholesterol




Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease.

Ridker PM, Stampfer MJ, Rifai N.

Brigham and Women's Hospital, 900 Commonwealth Ave E, Boston, MA 02215, USA. pridker partners.org

CONTEXT: Several novel risk factors for atherosclerosis have recently been proposed, but few comparative data exist to guide clinical use of these emerging biomarkers. OBJECTIVE: To compare the predictive value of 11 lipid and nonlipid biomarkers as risk factors for development of symptomatic peripheral arterial disease (PAD). DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study using plasma samples collected at baseline from a prospective cohort of 14 916 initially healthy US male physicians aged 40 to 84 years, of whom 140 subsequently developed symptomatic PAD (cases); 140 age- and smoking status-matched men who remained free of vascular disease during an average 9-year follow-up period were randomly selected as controls. MAIN OUTCOME MEASURE: Incident PAD, as determined by baseline total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol-HDL-C ratio, triglycerides, homocysteine, C-reactive protein (CRP), lipoprotein(a), fibrinogen, and apolipoproteins (apo) A-I and B-100. RESULTS: In univariate analyses, plasma levels of total cholesterol (P<.001), LDL-C (P =.001), triglycerides (P =.001), apo B-100 (P =.001), fibrinogen (P =.02), CRP (P =.006), and the total cholesterol-HDL-C ratio (P<.001) were all significantly higher at baseline among men who subsequently developed PAD compared with those who did not, while levels of HDL-C (P =.009) and apo A-I (P =.05) were lower. Nonsignificant baseline elevations of lipoprotein(a) (P =.40) and homocysteine (P =.90) were observed. In multivariable analyses, the total cholesterol-HDL-C ratio was the strongest lipid predictor of risk (relative risk [RR] for those in the highest vs lowest quartile, 3.9; 95% confidence interval [CI], 1.7-8.6), while CRP was the strongest nonlipid predictor (RR for the highest vs lowest quartile, 2.8; 95% CI, 1.3-5.9). In assessing joint effects, addition of CRP to standard lipid screening significantly improved risk prediction models based on lipid screening alone (P<.001). CONCLUSIONS: Of 11 atherothrombotic biomarkers assessed at baseline, the total cholesterol-HDL-C ratio and CRP were the strongest independent predictors of development of peripheral arterial disease. C-reactive protein provided additive prognostic information over standard lipid measures.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11368701&dopt=Abstract cholesterol




High density lipoprotein cholesterol and total cholesterol in children with asthma and allergic rhinitis.

Shenoi A, Kumar L, Sarihyan S, Gangully NK.

Department of Paediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Serum high density lipoprotein cholesterol and total cholesterol were studied in 15 children with allergic rhinitis, 45 asymptomatic asthmatic children and 16 children with acute asthmatic attacks. The latter were also studied in their asymptomatic phase. Two control groups of children with minor anatomical defects and those with acute pneumonia with respiratory distress were also studied. The serum concentrations of high density lipoprotein cholesterol were significantly higher (p less than 0.001) and those of total cholesterol lower (p less than 0.001) in children with respiratory allergy when compared to controls. The concentration of high density lipoprotein cholesterol increased and that of total cholesterol decreased during acute asthma.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1515759&dopt=Abstract cholesterol




Serum cholesterol in Wisconsin epidemiologic study of diabetic retinopathy.

Klein BE, Moss SE, Klein R, Surawicz TS.

University of Wisconsin, Department of Ophthalmology, Madison 53792.

OBJECTIVE--To describe serum total and high-density lipoprotein (HDL) cholesterol in a sample of people with diabetes. RESEARCH DESIGN AND METHODS--Subjects were those who participated in the 1984-1986 Wisconsin Epidemiologic Study of Diabetic Retinopathy. Data were from three groups of subjects: 304 younger-onset and 185 older-onset people taking insulin and 162 older-onset individuals not taking insulin. Serum lipids, duration of diabetes, glycosylated hemoglobin, diastolic blood pressure, sex, age, serum creatinine, units of insulin per kilogram per day, smoking status, serum C-peptide level, and alcohol use were analyzed statistically. RESULTS--In subjects taking insulin, glycosylated hemoglobin was correlated most strongly with total cholesterol. In those not taking insulin, C-peptide was correlated most strongly. In subjects taking insulin, the units used per day (fewer) and sex (female) were significantly associated with higher HDL cholesterol, and in both older-onset groups, serum C-peptide was significantly associated with lower HDL cholesterol. Mean total cholesterol levels were generally higher and mean HDL cholesterol levels were generally lower than those found in a nondiabetic comparison group. CONCLUSION--By the National Cholesterol Education Program guidelines, 17% of younger-onset and 30% of older-onset insulin users and 32% of older-onset subjects not taking insulin were in the high-risk range for total cholesterol. Lower levels of glycosylated hemoglobin might result in lower cholesterol levels.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1547687&dopt=Abstract cholesterol




Liver mevalonate 5-pyrophosphate decarboxylase is responsible for reduced serum cholesterol in stroke-prone spontaneously hypertensive rat.

Sawamura M, Nara Y, Yamori Y.

Department of Pathology, Shimane Medical University, Izumo, Japan.

Spontaneously hypertensive rat (stroke-prone) (SHRSP) has an interestingly low serum cholesterol level due to a reduced biosynthesis of cholesterol in the liver (Iritani, N., Fukuda, E., Nara, Y., and Yamori, Y. (1977) Atherosclerosis 28, 217-222). In this study, we examined the mechanism underlying the reduction of hepatic cholesterol biosynthesis in the rat. Our initial findings in SHRSP, as compared with normotensive Wistar Kyoto rat (WKY), showed that 1) the incorporation of [14C]acetate into cholesterol in the liver slices was markedly less, 2) 3-hydroxyl-3-methylglutaryl (HMG) CoA reductase activity was not reduced, and 3) the incorporation of [3H]mevalonic acid into both cholesterol and squalene was significantly less. The above initial findings suggested that the reduction in the hepatic cholesterol biosynthesis took place in one or more enzymatic processes starting with mevalonic acid and continuing to squalene. When the incorporation of [3H]mevalonic acid into phosphomevalonate derivatives was studied using an ion exchange column, only the radioactivity incorporated into isopentenyl-pyrophosphate (isopentenyl-PP) was less in SHRSP. Furthermore, the specific activity of diphosphomevalonate (mevalonate-PP) decarboxylase in the liver-soluble fractions was reduced 50% in SHRSP as compared with WKY. Kinetic studies using liver crude extracts indicated a lower Vmax value in SHRSP (SHRSP, 0.47; WKY, 2.05 nmol/min/mg), and an unchanged Km value (SHRSP, 18.2; WKY, 19.6 microM). The activity of mevalonate-PP decarboxylase was also found to be reduced in other tissues, including the brain, testis, small intestine, and cultured vascular smooth muscle cells. From the above observations, we concluded that the lower activity of mevalonate-PP decarboxylase was responsible for the reduced cholesterol biosynthesis in the liver of SHRSP.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1556116&dopt=Abstract cholesterol