L Berthou, B Staels, I Saldicco, K Berthelot, J Casey, J C Fruchart, P Denèfle, D Branellec
{"title":"Opposite in vitro and in vivo regulation of hepatic apolipoprotein A-I gene expression by retinoic acid. Absence of effects on apolipoprotein A-II gene expression.","authors":"L Berthou, B Staels, I Saldicco, K Berthelot, J Casey, J C Fruchart, P Denèfle, D Branellec","doi":"10.1161/01.atv.14.10.1657","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1657","url":null,"abstract":"<p><p>We studied the pharmacological potential of retinoids to modulate apolipoprotein (apo) A-I and apoA-II gene expression and production in vitro in the human cell line HepG2 as well as in primary cultures of adult rat hepatocytes and in vivo in the rat. In HepG2 cells, addition of all-trans retinoic acid (RA) doubled apoA-I mRNA within 24 hours and protein secreted in the culture medium after 48 hours. The induction of apoA-I mRNA by RA was completely blocked by actinomycin D, suggesting that RA acts at the transcriptional level in HepG2 cells. In primary cultures of rat hepatocytes, addition of RA increased apoA-I mRNA in a dose- and time-dependent manner as well as the secretion of apoA-I protein. Similar changes in apoA-I mRNA were observed with 9-cis RA. However, in vivo, hepatic apoA-I mRNA levels decreased after a single administration of RA at 10 mg/kg and remained low after prolonged treatment or at a higher dose, and serum apoA-I concentrations did not change. Furthermore, RA treatment did not substantially affect apoA-II mRNA levels or protein secretion either in vitro or in vivo. As a control, RA receptor-beta mRNA levels increased after RA both in vitro and in vivo. In conclusion, RA treatment selectively induces apoA-I and not apoA-II expression in vitro but not in vivo. These results therefore show additional regulatory effects of RA on apoA-I gene expression in vivo and raise questions about the usefulness of RA in the treatment of atherosclerosis.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1657-64"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18914730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L Tiret, P de Knijff, H J Menzel, C Ehnholm, V Nicaud, L M Havekes
{"title":"ApoE polymorphism and predisposition to coronary heart disease in youths of different European populations. The EARS Study. European Atherosclerosis Research Study.","authors":"L Tiret, P de Knijff, H J Menzel, C Ehnholm, V Nicaud, L M Havekes","doi":"10.1161/01.atv.14.10.1617","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1617","url":null,"abstract":"<p><p>The European Atherosclerosis Research Study was based on the comparison of offspring having a paternal history of premature myocardial infarction with age- and sex-matched control subjects. Case (n = 635) and control (n = 1259) subjects aged 18 through 26 years were recruited from 14 universities of 11 European countries. The allele distributions of apolipoprotein (apo) E polymorphism differed between populations, with a clear-cut gradient for allele epsilon 4 frequency decreasing from 0.18 in Finland to 0.11 in the south of Europe, following the gradient of coronary heart disease mortality rates. The association of apoE polymorphism with plasma total cholesterol, low-density lipoprotein cholesterol, apoB, and apoE levels was consistent with the now well-identified effects of epsilon 2 and epsilon 4 alleles on these traits. Both epsilon 2 and epsilon 4 alleles equally increased the level of triglycerides, and epsilon 2 had a lowering effect on lipoprotein(a) concentration. There were also weak effects of epsilon 2 and epsilon 4 on high-density lipoprotein cholesterol, apoA-I, and apoA-I-containing lipoprotein levels that paralleled those on apoE levels. The main finding of this study was the significant association of the apoE polymorphism with a paternal history of myocardial infarction. The association was consistent across regions, except in the south. When excluding this region, the population-adjusted odds ratios by reference to phenotype E3/3 were estimated as 0.23, 0.61, 0.78, 1.16, and 1.33 for E2/2, E3/2, E4/2, E4/3, and E4/4, respectively. The apoE locus largely explained the case/control difference of apoB level.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1617-24"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18916058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E R O'Brien, M R Garvin, D K Stewart, T Hinohara, J B Simpson, S M Schwartz, C M Giachelli
{"title":"Osteopontin is synthesized by macrophage, smooth muscle, and endothelial cells in primary and restenotic human coronary atherosclerotic plaques.","authors":"E R O'Brien, M R Garvin, D K Stewart, T Hinohara, J B Simpson, S M Schwartz, C M Giachelli","doi":"10.1161/01.atv.14.10.1648","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1648","url":null,"abstract":"<p><p>How an atherosclerotic plaque evolves from minimal diffuse intimal hyperplasia to a critical lesion is not well understood. Cellular proliferation is a relatively infrequent and modest event in both primary and restenotic coronary atherectomy specimens, leading us to believe that other processes, such as the formation of extracellular matrix, cell migration, neovascularization, and calcification might be more important for lesion formation. The investigation of proteins that are overexpressed in plaque compared with the normal vessel wall may provide clues that will help determine which of these processes are key to lesion pathogenesis. One such molecule, osteopontin (OPN), is an arginine-glycine-aspartate-containing acidic phosphoprotein recently shown to be a novel component of human atherosclerotic plaques and selectively expressed in the rat neointima following balloon angioplasty. Using in situ hybridization and immunohistochemical methods, we demonstrate that in addition to macrophages, smooth muscle and endothelial cells synthesize OPN mRNA and protein in human coronary atherosclerotic plaque specimens obtained by directional atherectomy. In contrast, OPN mRNA and protein were not detected in nondiseased vessel walls. Furthermore, extracellular OPN protein collocalized with sites of early calcification in the plaque that were identified with a sensitive modification of the von Kossa staining technique. These findings, combined with studies showing that OPN has adhesive, chemotactic, and calcium-binding properties, suggest that OPN may contribute to cellular accumulations and dystrophic calcification in atherosclerotic plaques.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1648-56"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18916062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B C Mortimer, T G Redgrave, E A Spangler, J G Verstuyft, E M Rubin
{"title":"Effect of human apoE4 on the clearance of chylomicron-like lipid emulsions and atherogenesis in transgenic mice.","authors":"B C Mortimer, T G Redgrave, E A Spangler, J G Verstuyft, E M Rubin","doi":"10.1161/01.atv.14.10.1542","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1542","url":null,"abstract":"<p><p>Apolipoprotein (apo) E is a ligand for lipoprotein receptors and mediates the cellular uptake of several different lipoproteins. Human apoE occurs in three allelic forms designated E2, E3, and E4. The E2 isoform is associated with changes in lipoprotein metabolism, and the E4 isoform is associated with Alzheimer's disease and an increased risk of coronary heart disease. In this study transgenic mice were generated to assess the effect of a sustained increase in plasma apoE4 concentration. The transgenic animals had three- to sixfold increases in total plasma apoE, associated primarily with the non-high-density lipoprotein (HDL) fractions of plasma lipoproteins. In response to an atherogenic diet the transgenic mice developed hypercholesterolemia similar to that in nontransgenic mice but did not experience the decrease in HDL cholesterol normally observed in this strain of C57BL/6 mice. The rate of plasma clearance of a lipid emulsion mimicking lymph chylomicrons was measured in transgenic mice expressing the human apoE4 gene and compared with the clearance rate in nontransgenic control animals. In animals fed a low-fat diet the emulsion lipids were cleared significantly more rapidly from the plasma of transgenic than control mice. In animals adapted to a high-fat diet, the clearance of chylomicron remnants was slowed markedly in both transgenic and control mice and was not significantly accelerated in transgenic compared with control animals. We also investigated the effect of increasing the plasma concentration of apoE4 on the progression of atherosclerotic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1542-52"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18915493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R P Dullaart, K Hoogenberg, B D Dikkeschei, A van Tol
{"title":"Higher plasma lipid transfer protein activities and unfavorable lipoprotein changes in cigarette-smoking men.","authors":"R P Dullaart, K Hoogenberg, B D Dikkeschei, A van Tol","doi":"10.1161/01.atv.14.10.1581","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1581","url":null,"abstract":"<p><p>The mechanism responsible for the atherogenic lipoprotein changes associated with cigarette smoking are largely unknown. Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of plasma cholesterol and the transfer of cholesteryl ester from high-density lipoproteins (HDLs) toward very-low- and low-density lipoproteins (VLDLs+LDLs). Another transfer factor, phospholipid transfer protein (PLTP), recently has been shown to be involved in the interconversion of HDL particles in vitro, but its physiological function is not yet clear. We measured the activities of LCAT, CETP (as cholesteryl ester exchange activity), and PLTP using exogenous substrate assays as well as lipoprotein profiles in the plasma of 21 normolipidemic cigarette-smoking men (total plasma cholesterol below 6.5 mmol/L and triglyceride below 2.5 mmol/L) and 21 individually matched nonsmoking control subjects. HDL cholesterol, HDL cholesteryl ester, and plasma apolipoprotein A-I levels were lower in the smokers than in the control subjects (P < or = .05 for all parameters). Median plasma CETP activity was 18% higher (P < .02) and median plasma PLTP activity was 8% higher (P < .05) in the smokers compared with the nonsmokers. LCAT activity was not different between the groups. HDL cholesteryl ester concentration was positively related to LCAT activity in control subjects but not in smokers. By contrast, there was an inverse relation of CETP activity with HDL cholesteryl ester in smokers but not in nonsmokers. Multiple regression analysis demonstrated that the lowering effect of smoking on HDL cholesteryl ester could be explained by its influence on CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1581-5"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1581","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18915498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G Franceschini, M Cassinotti, G Vecchio, G Gianfranceschi, F Pazzucconi, T Murakami, M Sirtori, A L D'Acquarica, C R Sirtori
{"title":"Pravastatin effectively lowers LDL cholesterol in familial combined hyperlipidemia without changing LDL subclass pattern.","authors":"G Franceschini, M Cassinotti, G Vecchio, G Gianfranceschi, F Pazzucconi, T Murakami, M Sirtori, A L D'Acquarica, C R Sirtori","doi":"10.1161/01.atv.14.10.1569","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1569","url":null,"abstract":"<p><p>Familial combined hyperlipidemia (FCHL) is the most common genetic lipid disorder among young survivors of myocardial infarction. Elevations of plasma total and low-density lipoprotein (LDL) cholesterol and the prevalence of small, dense LDL particles are both involved in the high coronary risk of FCHL patients. We investigated the ability of pravastatin to favorably correct plasma lipid and lipoprotein levels and LDL structure in FCHL patients. Twelve patients with FCHL, documented by studies of first-degree relatives, received pravastatin (40 mg/d) for 12 weeks. Pravastatin significantly lowered plasma total and LDL cholesterol levels by 21% and 32%, respectively. Triglyceride levels did not change, and apolipoprotein B (apoB) concentrations decreased by 9% (P = NS). High-density lipoprotein (HDL) cholesterol increased by 6% because of a significant 73% rise of HDL2 cholesterol. LDL were smaller (diameter, 24.5 +/- 0.5 nm), less buoyant, and apoB-rich (cholesteryl ester-apoB ratio, 1.64 +/- 0.46) in the selected patients compared with patients with familial hypercholesterolemia or healthy control subjects. LDL became even smaller (23.8 +/- 0.6 nm) and richer in apoB (cholesteryl ester-apoB ratio, 1.27 +/- 0.52) after pravastatin treatment. Although pravastatin favorably altered plasma lipid and lipoprotein levels in FCHL patients, the abnormal LDL particle distribution and composition were not affected. Because of the apparent resistance of the small, dense LDL to drug-induced modifications, a maximal lipid-lowering effect is needed to reduce coronary risk in FCHL patients.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1569-75"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18915496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E Tremoli, S Eligini, S Colli, P Maderna, P Risè, F Pazzucconi, F Marangoni, C R Sirtori, C Galli
{"title":"n-3 fatty acid ethyl ester administration to healthy subjects and to hypertriglyceridemic patients reduces tissue factor activity in adherent monocytes.","authors":"E Tremoli, S Eligini, S Colli, P Maderna, P Risè, F Pazzucconi, F Marangoni, C R Sirtori, C Galli","doi":"10.1161/01.atv.14.10.1600","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1600","url":null,"abstract":"<p><p>n-3 Fatty acids are known to influence several functions of monocytes, including adhesion, cytokine synthesis, and superoxide generation. Monocytes express tissue factor, a membrane-bound glycoprotein, that acts as a catalyst in the coagulation cascade. In this study we evaluated the effects of administration of n-3 fatty acid ethyl esters to healthy volunteers and to hypertriglyceridemic patients on tissue factor activity (TF activity) in adherent monocytes. n-3 Fatty acids containing 75% eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (ratio of EPA to DHA, 1.34) were administered (3 g/d) to normal volunteers for 18 weeks. In addition, the effects of this treatment were evaluated in 30 hypertriglyceridemic patients for 24 weeks by using a double-blind, placebo-controlled study. TF activity in adherent monocytes was evaluated with a one-stage clotting assay. Plasma and monocyte fatty acid compositions were determined by gas-liquid chromatography. In healthy volunteers, n-3 fatty acids significantly reduced TF activity in adherent monocytes either in the unstimulated condition or after exposure to endotoxin. The inhibitory effect was observed after 12 weeks of treatment and was more pronounced after 18 weeks (> 70%, P < .001 versus baseline). Concomitantly, levels of EPA and DHA increased in plasma and monocyte lipids. Interestingly, after stopping treatment, monocyte TF activity remained inhibited for at least 14 weeks. Treatment with n-3 fatty acids for 24 weeks also resulted in a significant reduction of TF activity in adherent monocytes from hypertriglyceridemic patients (-31% and -40% in unstimulated and endotoxin-stimulated cells; P < .05 versus baseline).(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1600-8"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18916056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association of apolipoprotein(a) phenotypes in children with family history of premature coronary artery disease.","authors":"S Islam, B Gutin, C Smith, F Treiber, M I Kamboh","doi":"10.1161/01.atv.14.10.1609","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1609","url":null,"abstract":"<p><p>Although blacks have higher plasma levels of lipoprotein(a) [Lp(a)] than whites, the Lp(a) levels are not associated with clinical coronary artery disease (CAD) or parental history of myocardial infarction in blacks. To explore whether ethnic differences in the pathogenicity of Lp(a) are related to the thrombogenic component of Lp(a), this study investigated in children the associations of apolipoprotein(a) [apo(a)] phenotypes and Lp(a) levels with family history of premature CAD. Subjects were 46 children aged 7 to 11 years divided according to family history of premature CAD and assessed for Lp(a), apo(a) phenotypes, and other lipids and lipoproteins. The prevalence of small isoforms was higher in children with positive family history of premature CAD than in children with negative family history of premature CAD (32% versus 10%). Large isoforms were more prevalent in whites (24% versus 6%), and medium-sized isoforms were more prevalent in blacks (75% versus 52%). The black/white difference was smaller (19% versus 24%) in regard to small isoforms. Lp(a) levels were inversely related to apo(a) size in both blacks and whites (P = .084 and P = .049, respectively). Single-banded small apo(a) isoforms predicted positive family history of premature CAD, independent of ethnicity and Lp(a) levels. Small apo(a) isoforms in children were independent predictors of family history of premature CAD. Unlike Lp(a), they appear to be equally pathogenic for blacks and whites.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1609-16"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18916057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R Salonen, M Tervahauta, J T Salonen, J Pekkanen, A Nissinen, M J Karvonen
{"title":"Ultrasonographic manifestations of common carotid atherosclerosis in elderly eastern Finnish men. Prevalence and associations with cardiovascular diseases and risk factors.","authors":"R Salonen, M Tervahauta, J T Salonen, J Pekkanen, A Nissinen, M J Karvonen","doi":"10.1161/01.atv.14.10.1631","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1631","url":null,"abstract":"<p><p>We investigated the prevalence and associations with cardiovascular symptoms, signs, and risk factors of common carotid atherosclerosis using B-mode ultrasonography in a population sample of 182 eastern Finnish men aged 70 to 89 years. Men were examined in 1989 as a part of the 30-year follow-up examination of the eastern Finnish cohort of the Seven Countries Study. The mean maximal intima-media thickness (IMT) of the right and left common carotid arteries was 1.5 mm (range, 0.7 to 5.3 mm; standard deviation, 0.7 mm). Fifty-one percent of the subjects had nonmineralized atheroma and 91% had single or multiple mineralizations in any of the arterial segments imaged. Both mean maximal IMT and nonmineralized atheromas were associated significantly (P < .05) with the presence of cerebral atherosclerosis, carotid murmur, at least one nonpalpable peripheral arterial pulse, ischemic resting electrocardiographic abnormalities, and history of coronary heart disease but not with intermittent claudication at the 30-year follow-up. No significant associations were found between carotid mineralizations and clinical cardiovascular disease. Long-term elevations of serum cholesterol and long-term smoking, measured as the number of risk factor elevations in the six examinations, were associated with the presence of nonmineralized atheroma in the elderly (in 1989). Smoking and repeatedly detected hypertension, on the other hand, had an association with the presence of mineralizations in 1989.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1631-40"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1631","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18916060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hyperinsulinemia, risk factors, and coronary heart disease. The Zutphen Elderly Study.","authors":"E J Feskens, D Kromhout","doi":"10.1161/01.atv.14.10.1641","DOIUrl":"https://doi.org/10.1161/01.atv.14.10.1641","url":null,"abstract":"<p><p>We investigated the association between fasting insulin concentration--an indicator of insulin resistance in nondiabetic individuals--cardiovascular risk factors, and coronary heart disease in a study of 390 men in the town of Zutphen. In 1990, an extensive examination was carried out on the participating men (aged 70 to 89 years). Fasting insulin levels were determined and a number of other risk factors measured. Known and newly diagnosed diabetics were excluded from the data analyses. Fasting insulin concentration was significantly associated with levels of glucose, triglycerides, uric acid, serum albumin, creatinine, and fibrinogen as well as resting heart rate. Inverse associations with high-density lipoprotein cholesterol and factor VII activity were observed. These results were independent of confounding factors such as age, body mass index, ratio of subscapular to triceps skinfold thicknesses, cigarette smoking, physical activity, and alcohol consumption. Men with a fasting insulin level higher than 80 pmol/L (highest quartile of the distribution) had a significantly higher prevalence of coronary heart disease and especially of myocardial infarction. This result was independent of potential confounding variables as well as of possible intermediates (total and high-density lipoprotein cholesterol, hypertension, serum triglycerides, fasting glucose, and other risk factors related to fasting insulin) (odds ratio, 2.2; 95% confidence interval, 1.2-4.0). No association between fasting insulin level and hypertension or blood pressure was observed. These results show that fasting insulin is an important indicator of coronary heart disease in elderly men. Clotting factors, resting heart rate, uric acid, serum albumin, and creatinine may also play a role in this metabolic syndrome.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 10","pages":"1641-7"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.10.1641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18916061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}