Higher Plasma Triglyceride Levels Research Articles

Endothelium-dependent relaxation by acetylcholine is impaired in hypertriglyceridemic humans with normal levels of plasma LDL cholesterol

OBJECTIVESPatients with high triglyceride (of which very low density lipoproteins [VLDL] are the main carriers), but with normal low density lipoprotein (LDL) cholesterol levels, were examined for in vivo endothelium function status.BACKGROUNDVery low density lipoproteins inhibit endothelium-dependent, but not -independent, vasorelaxation in vitro.METHODSThree groups were studied: 1) healthy volunteers (n = 10; triglyceride 1.24 ± 0.14 mmol/liter, LDL cholesterol 2.99 ± 0.24 mmol/liter); 2) hypertriglyceridemic (n = 11; triglyceride 6.97 ± 1.19 mmol/liter,∗ LDL cholesterol 2.17 ± 0.2 mmol/liter, ∗p < 0.05); and 3) hypercholesterolemic (n = 10; triglyceride 2.25 ± 0.29 mmol/liter,∗ LDL cholesterol 5.61 ± 0.54 mmol/liter∗; ∗p < 0.05) patients. Vasoactive responses to acetylcholine, sodium nitroprusside, noradrenaline, NG-monomethyl-l-arginine and postischemic hyperemia were determined using forearm venous occlusion plethysmography.RESULTSResponses to acetylcholine (37 μg/min) were significantly dampened both in hypercholesterolemic (% increase in forearm blood flow: 268.2 ± 62) and hypertriglyceridemic patients (232.6 ± 45.2) when compared with controls (547.8 ± 108.9; ANOVA p < 0.05). Responses to sodium nitroprusside (at 1.6 μg/min: controls vs. hypercholesterolemics vs. hypertriglyceridemic: 168.7 ± 25.1 vs. 140.6 ± 38.9 vs. 178.5 ± 54.5% increase), noradrenaline, NG-monomethyl-l-arginine and postischemic hyperemic responses were not different among the groups examined.CONCLUSIONSAcetylcholine responses are impaired in patients with pathophysiologic levels of plasma triglycerides but normal plasma levels of LDL cholesterol. The impairment observed was comparable to that obtained in hypercholesterolemic patients. We conclude that impaired responses to acetylcholine normally associated with hypercholesterolemia also occur in hypertriglyceridemia. These findings identify a potential mechanism by which high plasma triglyceride levels may be atherogenic independent of LDL cholesterol levels.

Prevalence and sociodemographic determinants of cardiovascular risk in a rural area.

Non-metropolitan areas have a higher mortality from cardiovascular disease than metropolitan areas. The study's aim was to establish the prevalence of cardiovascular disease risk factors in a rural area and identify their sociodemographic determinants. Adults, randomly selected from Ballarat's electoral rolls, were invited to complete a questionnaire and have their height, weight, blood pressure and fasting lipids measured. Three hundred and thirty-eight eligible persons participated (67% response). The data were analysed using logistic and multiple regression analyses. Increasing age was associated with hypertension, high plasma cholesterol, overweight/obesity, high plasma triglyceride levels and increasing plasma fibrinogen. Women were less likely to be overweight/obese and have a high plasma triglyceride. Not having completed high school was associated with hypertension, high plasma cholesterol and triglyceride levels and physical inactivity. Smoking was associated with employment and being in a non-professional/managerial occupation. Rural health promotion initiatives should take account of the needs of these population subgroups.

Association of the inflammatory state in active juvenile rheumatoid arthritis with hypo-high-density lipoproteinemia and reduced lipoprotein-associated platelet-activating factor acetylhydrolase activity.

To investigate the relationship between the quantitative and qualitative abnormalities of apolipoprotein B (Apo B)- and Apo A-I-containing lipoproteins and between lipoprotein-associated platelet-activating factor acetylhydrolase (PAF-AH) activity in patients with juvenile rheumatoid arthritis (JRA) as a function of the inflammatory state. Twenty-six JRA patients and 22 age- and sex-matched control subjects with normal lipid levels participated in the study. Fourteen patients had active disease, and 12 had inactive disease. Plasma lipoproteins were fractionated by gradient ultracentrifugation into 9 subfractions, and their chemical composition and mass were determined. The PAF-AH activity associated with lipoprotein subfractions and the activity in plasma were also measured. Patients with active JRA had significantly lower plasma total cholesterol and high-density lipoprotein (HDL) cholesterol levels as compared with controls, due to the decrease in the mass of both the HDL2 and HDL3 subfractions. Patients with active JRA also had higher plasma triglyceride levels, mainly due to the higher triglyceride content of the very low-density lipoprotein plus the intermediate-density lipoprotein subfraction. The plasma PAF-AH activity in patients with active JRA was lower than that in controls, mainly due to the decrease in PAF-AH activity associated with the intermediate and dense low-density lipoprotein subclasses. The lipid abnormalities and the reduction in plasma PAF-AH activity were significantly correlated with plasma C-reactive protein levels and were not observed in patients with inactive JRA. This is the first study to show that patients with active JRA exhibit low levels of HDL2 and HDL3 and are deficient in plasma PAF-AH activity. These alterations suggest that active JRA is associated with partial loss of the antiinflammatory activity of plasma Apo B- and Apo A-I-containing lipoproteins.

Cardiovascular disease and risk factors in adults with hypopituitarism.

In 1992, Cuneo et al. (1992) reviewed, in this journal, the consequences of growth (GH) deficiency during adult life and coined the term ‘Growth hormone deficiency (GHD) syndrome in adults’. Limited information was available then on cardiovascular disease and risk factors in adults with hypopituitarism. More data have been published since on cardiovascular morbidity in symptom-free hypopituitary adults. Several groups have also published results on the effects of GH therapy on cardiac structure and function and on the cardiovascular risk factors. We shall review here the epidemiological and experimental data on cardiovascular morbidity and mortality in adult hypopituitarism. We shall also examine the prevalence of cardiovascular risk factors in this group of patients and their potential causes focusing on the possible role of GH deficiency and the effects of GH replacement.

Apolipoprotein E2 Reduces the Low Density Lipoprotein Level in Transgenic Mice by Impairing Lipoprotein Lipase-mediated Lipolysis of Triglyceride-rich Lipoproteins

Apolipoprotein (apo) E2 is often associated with low levels of low density lipoprotein (LDL) cholesterol and high levels of plasma triglycerides in humans. Mice expressing apoE2 also have low LDL levels. To evaluate the possible role of the LDL receptor in the cholesterol-lowering effect of apoE2, we bred transgenic mice expressing low levels of apoE2 with LDL receptor-null mice (hE2(+/0), LDLR-/-). Even in the absence of the LDL receptor, plasma total and LDL cholesterol levels decreased progressively with increasing levels of plasma apoE2. At plasma apoE2 levels >20 mg/dl, LDL cholesterol was approximately 45% lower than in LDLR-/- mice. Thus, the LDL cholesterol-lowering effect of apoE2 is independent of the LDL receptor. In contrast, plasma triglyceride levels increased (mostly in very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL)) progressively as apoE2 levels increased. At plasma apoE2 levels >20 mg/dl, triglycerides were approximately 150% higher than in LDLR-/- mice. Furthermore, in apoE-null mice (hE2(+/0), mE-/-), apoE2 levels also correlated positively with plasma triglyceride levels, suggesting impaired lipolysis in both hE2(+/0),LDLR-/- and hE2(+/0),mE-/- mice. Incubating VLDL or IDL from the hE2(+/0),LDLR-/- or the hE2(+/0),mE-/- mice with mouse postheparin plasma inhibited lipoprotein lipase-mediated lipolysis of apoE2-containing VLDL and IDL by approximately 80 and approximately 70%, respectively, versus normal VLDL and IDL. This observation was confirmed by studies with triglyceride-rich emulsion particles, apoE2, and purified lipoprotein lipase. Furthermore, apoE2-containing VLDL had much less apoC-II than normal VLDL. Adding apoC-II to the incubation partially corrected the apoE2-impaired lipolysis in apoE2-containing VLDL or IDL and corrected it completely in apoE2-containing emulsion particles. Thus, apoE2 lowers LDL cholesterol by impairing lipoprotein lipase-mediated lipolysis of triglyceride-rich lipoproteins (mostly by displacing or masking apoC-II). Furthermore, the effects of apoE2 on both plasma cholesterol and triglyceride levels are dose dependent and act via different mechanisms. The increase in plasma cholesterol caused by apoE2 is due mostly to impaired clearance, whereas the increase in plasma triglycerides is caused mainly by apoE2-impaired lipolysis of triglyceride-rich lipoproteins.

The Atherogenic Significance of an Elevated Plasma Triglyceride Level

The importance of hypertriglyceridemia as an independent predictor of coronary artery disease (CAD) remains unsettled. Hypertriglyceridemia, with or without associated hypercholesterolemia, occurs more frequently in premature CAD subjects than does hypercholesterolemia alone. With univariate analysis, most studies show a positive correlation between plasma triglyceride (TG) level and risk for CAD, but with multivariate analysis plasma TG level is no longer an independent risk factor except in women and diabetics. Prospective studies have shown that subjects with a high LDL/HDL cholesterol ratio and a high plasma TG level have the highest risk for CAD.Hypertriglyceridemia signifies the presence of excess triglyceride-rich lipoproteins (TRL), including chylomicrons, VLDL, and their remnants. The question then becomes one of whether TRL are directly or indirectly involved in atherogenesis. TRL were thought to be too big to infiltrate the arterial wall, and histopathological studies have shown cholesterol but not triglyceride accumulation in the atherosclerotic plaque. However, there was a recent demonstration of undegraded VLDL and IDL in atherosclerotic plaques. Larger TRL may undergo hydrolysis on the arterial surface to become smaller particles before entry into the intima. Possible cellular pathways for the uptake of TRL by macrophages have been described. The smaller TRL (Sf 20–60), including postprandial chylomicron remnants, are believed to be the most atherogenic of all TRL particles. Because large amounts of TRL are produced in the postprandial period, atherogenesis involving TRL may be primarily a postprandial phenomenon. Once in the intima, TG may undergo hydrolysis, releasing free fatty acids and mono-and diacyl glycerol, accounting for the dearth of TG in atherosclerotic lesions. Particle for particle, VLDL delivers five times as much cholesterol as LDL does to the macrophage.TRL also have an indirect influence on atherogenesis by having a profound effect on LDL and HDL. In hypertriglyceridemic states, there is an enhanced transfer of TG from TRL to LDL and HDL in exchange for cholesterol esters. The TG-enriched LDL and HDL particles become preferred substrates for hepatic lipase that converts them to smaller and denser LDL and HDL particles. Small, dense LDL particles are particularly atherogenic, and smaller HDL particles are catabolized more readily, giving rise to a low HDL cholesterol. Hypertriglyceridemia may also cause CAD through other pathological processes such as increased coagulability, impaired fibinolysis, impaired endothelial function, and activation of adhesion and chemotactic factors.Hypertriglyceridemia (HTG) should not be ignored especially in secondary prevention. HTG with a high LDL/HDL cholesterol ratio signifies the highest risk.

Hyperinsulinemia and Abdominal Obesity Affect the Expression of Hypertriglyceridemia in Heterozygous Familial Lipoprotein Lipase Deficiency

We have reported three missense mutations (G188E, P207L, and D250N) in the lipoprotein lipase (LPL) gene among French-Canadians, resulting in the absence of measurable postheparin plasma LPL activity in homozygotes. Presence of triglyceride- and cholesterol-rich VLDL, as well as cholesterol-poor HDL particles, has been shown in heterozygotes affected by partial reduction in postheparin LPL activity. However, significant heterogeneity in their plasma triglyceride levels has been found, even among individuals carrying the same LPL gene mutation, indicating that factors other than LPL deficiency could affect the phenotypic expression of hypertriglyceridemia in the heterozygous state. The aim of the present study was to examine the combined effects of abdominal fat accumulation and hyperinsulinemia on plasma triglyceride levels among heterozygous patients for familial LPL deficiency. Based on sex and BMI, 43 heterozygotes (25 women and 18 men) were matched with noncarrier control subjects. Our data indicate that heterozygotes with higher abdominal fat deposition, as defined as waist girth values above the 50th percentile, had higher plasma triglyceride levels than nonobese heterozygotes. However, an important proportion of male heterozygote subjects were hypertriglyceridemic, even in absence of abdominal obesity, suggesting that another factor(s) was involved in the modulation of hypertriglyceridemia in these subjects. Indeed, multivariate analyses revealed that fasting hyperinsulinemia was a significant correlate of hypertriglyceridemia among these heterozygotes. Results of the present study indicate that abdominal obesity and hyperinsulinemia both have deleterious effects on plasma triglyceride levels in familial LPL deficiency. It is suggested that heterozygotes with moderate obesity and/or insulin resistance may be at higher risk of coronary artery disease because of the expression of an atherogenic lipoprotein phenotype among these patients.

Atherogenic lipoprotein changes in the absence of hyperlipidemia in patients with chronic renal failure treated by hemodialysis

We compared plasma lipid and lipoprotein parameters between 210 chronic renal failure patients treated by hemodialysis and 223 age- and sex-matched healthy control subjects to examine whether atherogenic lipoprotein changes were present in hemodialysis patients in the absence of hyperlipidemia. The hemodialysis group showed higher levels of plasma triglycerides, very low density lipoprotein (VLDL) cholesterol, and intermediate density lipoprotein (IDL) cholesterol and a lower level of high density lipoprotein (HDL) cholesterol. Low density lipoprotein (LDL) cholesterol of the hemodialysis group was not elevated but their LDL was significantly more triglyceride-enriched than that of controls. Subjects were then divided into five categories according to their plasma triglyceride levels at an interval of 50 mg/dl, and comparison was made between the two groups in the same range of plasma triglycerides. Hemodialysis patients again showed higher levels of VLDL- and IDL-cholesterol, and lower levels of HDL-cholesterol than the control group even in the plasma triglycerides-matched comparisons. Similarly, higher VLDL- and IDL-cholesterol levels in hemodialysis patients were significant in plasma total cholesterol-matched subgroup comparisons. Multiple regression analysis indicated that the relationship between plasma lipid concentrations and individual lipoprotein levels were substantially altered in uremic state. The 95th percentile level of IDL-cholesterol in the nonuremic controls was 15 mg/dl, and 45% of hemodialysis patients exceeded this level. Decreased HDL-cholesterol levels ≤35 mg/dl were seen in 6% of the control and 38% of the hemodialysis group. Elevated IDL-cholesterol and decreased HDL-cholesterol were persistently found in hemodialysis patients with normal lipid levels. It is concluded that hemodialysis patients exhibited more atherogenic lipoprotein profile than nonuremic subjects with comparable levels of plasma triglycerides and total cholesterol. Especially, increased IDL- and decreased HDL-cholesterol levels in hemodialysis patients persisted even at very low levels of plasma lipids. Since elevated IDL and decreased HDL-cholesterol are implicated in the progression of atherosclerosis, these findings are of clinical importance in the diagnosis of lipoprotein disorder in chronic renal failure.

Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV.

Transgenic mouse lines carrying several copies of the mouse apo A-IV gene were produced. Lipoprotein composition and function, and aortic lesion development were examined. Apo A-IV levels in the plasma of transgenic mice were elevated threefold compared with nontransgenic littermates on a chow diet, and sixfold in mice fed an atherogenic diet. Plasma concentrations of total cholesterol, HDL cholesterol, triglycerides, and free fatty acids were similar in transgenic and control mice fed a chow diet. However, with the atherogenic diet, male transgenic mice exhibited significantly higher levels of plasma triglycerides (P < 0.05), total cholesterol (P < 0.01), HDL cholesterol (P < 0.0001), and free fatty acids (P < 0.05), and lower levels of unesterified cholesterol (P < 0.05), than nontransgenic littermates. Expression of the apo A-IV transgene had a protective effect against the formation of diet-induced aortic lesions, with transgenics exhibiting lesion scores of approximately 30% those seen in control mice. HDL-sized lipoproteins isolated from transgenic mice fed the atherogenic diet promoted cholesterol efflux from cholesterol-loaded human monocytes more efficiently than comparable lipoproteins from nontransgenic counterparts. Plasma from transgenics also exhibited higher endogenous cholesterol esterification rates. Taken together, these results suggest that apo A-IV levels influence the metabolism and antiatherogenic properties of HDL.

A G +1 to C mutation in a donor splice site of intron 2 in the apolipoprotein (apo) C-II gene in a patient with apo C-II deficiency : A possible interaction between apo C-II deficiency and apo E4 in a severely hypertriglyceridemic patient

Familial apolipoprotein C-II (apo C-II) deficiency is an autosomal recessive genetic disorder characterized by fasting hypertriglyceridemia and accumulation of chylomicrons in the plasma. To elucidate the genetic defect, the apo C-II gene of a neonatal Japanese patient (C-II Tokyo) was analyzed. Nucleotide sequence analysis showed a G +1 to C transversion at the donor splice site of intron 2 (INT2 G +1 to C). Restriction fragment length polymorphism analyses of the patient's family members with Hph I showed that the patient was homozygous and the parents were heterozygous for the INT2 G +1 to C mutation. Although consanguinity could not be demonstrated, haplotype analysis of the C-II gene revealed the identity of the patient's alleles on the mutation, suggesting that the parents had a common Japanese ancestor. Sequence analysis of the patient's cDNA isolated from peripheral blood lymphocytes revealed that the INT2 G +1 to C mutation causes skipping of exon 2, which encodes the initiation codon, and results in deficiency of apo C-II proteins. The outstanding feature of our patient was that he showed severe hypertriglyceridemia beginning in the neonatal period, a feature not reported in a case of apo C-II deficiency (C-II Hamburg) with the same mutation as our patient. A previous report of another case of apo C-II deficiency (C-II Toronto) suggested that the apo E4 isoform is associated with higher levels of plasma triglycerides in subjects heterozygous for the apo C-II mutation. Determination of the apo E isoform of our patient revealed that apo E4 was coinherited with the INT2 G +1 to C mutation, whereas the apo E isoform has been reported to be E2/3 in C-II Hamburg. We speculate that apo E4/4 aggravated the hypertriglyceridemia in our patient with apo C-II deficiency.

Intralymphocyte free magnesium in a group of subjects with essential hypertension.

Despite the importance of magnesium in essential hypertension, few data are available on the ionized intracellular concentration of this ion. We therefore studied intralymphocyte free intracellular magnesium (Mgi) in 32 untreated essential hypertensive subjects and 27 normotensive control subjects by means of a fluorimetric technique based on the use of the new magnesium-sensitive dye furaptra. We also measured intralymphocyte ionized calcium (Cai) with fura 2. No statistically significant differences were found in Mgi in hypertensive compared with normotensive subjects (essential hypertensive, 0.291 +/- 0.053 mmol/L; normotensive, 0.293 +/- 0.043 [mean +/- SD]). A statistically significant inverse correlation was established between Mgi and plasma triglycerides in essential hypertensive subjects (r = -.521, P = .002). The hypertensive group was arbitrarily divided into two subgroups according to plasma triglyceride levels (> 2 [n = 10] or < 2 mmol/L [n = 22]), and Mgi proved to be significantly lower in the subgroup with high plasma triglyceride levels compared with either the subgroup with normal triglycerides (P = .009; 95% confidence interval, 0.013-0.088) or the normotensive control group as a whole (P = .03; 95% confidence interval, 0.003-0.069) (high-triglyceride hypertensive subgroup, Mgi = 0.256 +/- 0.045 mmol/L; normal-triglyceride hypertensive subgroup, Mgi = 0.307 +/- 0.049). No statistically significant differences were found in Cai in hypertensive compared with normotensive subjects (hypertensive, 53 +/- 12 nmol/L; normotensive, 54 +/- 14). We did not find statistically significant correlations between Cai and plasma triglycerides, nor did we find any differences in Cai between the subgroup of hypertensive subjects with high plasma triglyceride levels and either the subgroup of hypertensive subjects with normal triglycerides or the normotensive control group as a whole. The discrepancies between our results in lymphocytes and data relating to either erythrocytes or platelets emphasize the need for caution before the results are extrapolated from one tissue to the other. The decreased Mgi levels in the subgroup of high-triglyceride hypertensive subjects may suggest a role for magnesium in plurimetabolic syndrome.

Compositional Differences of LDL Particles in Normal Subjects With LDL Subclass Phenotype A and LDL Subclass Phenotype B

A predominance of small LDL particles (subclass phenotype B), as determined by gradient-gel electrophoresis is found among patients with myocardial infarction. Despite physical differences in phenotype A and B particles, differences in lipid composition of particles in these phenotypes have yet to be reported in an unselected population of males and females. The present study used lipid/apoB ratios to analyze the amount of lipid per LDL particle, isolated by density-gradient ultracentrifugation, in 70 healthy subjects. Relative to apoB, the LDL particles from phenotype B subjects were found to contain less free cholesterol (0.391 +/- 0.05 versus 0.465 +/- 0.05; mean +/- SD; P < .001), phospholipid (1.26 +/- 0.2 versus 1.43 +/- 0.2; P < .001), and cholesteryl ester (1.97 +/- 0.1 versus 2.11 +/- 0.2; P < .001) than particles from phenotype A subjects. The amount of triglyceride per LDL particle did not differ between the two phenotypes (0.410 +/- 0.1 versus 0.406 +/- 0.1; P = NS) despite higher plasma triglyceride levels in the phenotype B subjects. LDL size and buoyancy were positively correlated with particle free cholesterol, phospholipid, and cholesteryl ester but not with particle triglyceride. These data suggest that the physical properties of LDL from subjects with phenotype A and B reflect their lipid composition. The compositional differences between LDL particles of the two phenotypes may provide new insight into the increased risk of myocardial infarction in subjects with small, dense LDL.

Hyperinsulinemia and insulin resistance are associated with multiple abnormalities of lipoprotein subclasses in glucose-tolerant relatives of NIDDM patients. Botnia Study Group.

We studied the subclasses of plasma lipoproteins in normolipidemic, glucose-tolerant male relatives of noninsulin dependent diabetic patients (NIDDM), who represented either the lowest (n = 14) or the highest (n = 18) quintiles of fasting plasma insulin. The higher plasma triglyceride level in the high insulin group (1.61 mmol/l vs. 0.87 mmol/l, P < 0.001) was due to multiple differences in triglyceride-rich lipoproteins. The concentrations of larger VLDL1, smaller VLDL2 particles, and IDL particles were 3.8-fold, 2.5-fold, and 1.5-fold higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In addition, hyperinsulinemic subjects had VLDL1, VLDL2, and IDL particles enriched in lipids and poor in protein. The lower plasma HDL cholesterol level in the high insulin group (1.20 mmol/l vs. 1.44 mmol/l, P < 0.01) compared to the low insulin group was a consequence of a 27% reduction of HDL2a concentration (P < 0.05) and a significantly reduced percentage of cholesterol in HDL3a, HDL3b, and HDL3c subclasses. On the other hand, the percentages of triglycerides in HDL2b, HDL2a, HDL3a, and HDL3b subclasses were 76%, 79%, 61%, and 50% higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In the combined group, the concentration of VLDL1 and VLDL2 correlated positively with the concentrations of LDL2 and LDL3 and negatively with HDL2b and HDL2a subclasses (P < 0.05 or less). In conclusion, normolipidemic, glucose-tolerant but hyperinsulinemic relatives of NIDDM patients have qualitatively similar lipoprotein abnormalities as NIDDM patients. These abnormalities are not observed in insulin-sensitive relatives, suggesting that they develop in concert with insulin resistance.

Clinical Factors and Angiographic Features Associated With Premature Coronary Artery Disease

Clinical, angiographic, and biochemical features may differ in young patients with coronary heart disease compared with older patients. We compared clinical and angiographic characteristics in 100 male patients with clinical onset of disease at age < or = 45 years (group 1) with those of 100 older male patients (clinical onset of disease at > or = 60 years) (group 2). All patients had documented coronary artery disease. The two patient groups were compared in terms of the pattern of angina at disease onset, angiographic features, and coronary risk factors. Seventy-six patients in group 1 and 49 patients in group 2 presented with acute coronary syndromes (unstable angina or myocardial infarction) at clinical disease onset (p < 0.001). Compared with patients in group 2, younger patients (group 1) showed a preponderance of single-vessel disease (54 vs 36%; p < 0.001) and complex stenosis morphologic features (59 vs 36%; p < 0.01). Family history of coronary artery disease (39 vs 11%; p < 0.001) and smoking (73 vs 46%; p < 0.001) were also more prevalent in younger patients. Mean plasma total cholesterol level was 6.4 +/- 1.3 mmol/L in group 1 and 6.1 +/- 1.2 mmol/L in group 2 (p = NS). Younger patients, however, had lower high-density lipoprotein (HDL) cholesterol (0.9 +/- 0.2 mmol/L and 1.1 +/- 0.4 mmol/L; p < 0.01) and higher plasma triglyceride levels compared with patients of group 2 (2.7 +/- 1.3 mmol/L vs 2.1 +/- 1.1 mmol/L; p < 0.001). Patients with premature coronary disease referred to coronary angiography commonly have unheralded acute onset of symptoms, angiographically complex stenosis morphologic features, and less extensive coronary artery disease. In addition to previously identified risk factors such as family history and smoking, we observed that high plasma triglyceride and low HDL cholesterol levels are associated with premature coronary artery disease.

Risk factors for exercise-induced silent myocardial ischemia in healthy volunteers

This study determined the risk factors for exercise-induced silent ischemia (SI) in 281 apparently healthy volunteers aged 40 to 87 years and compared their risk factor profiles with those of 132 patients with overt coronary artery disease (CAD). SI (concordant exercise-induced asymptomatic ST-segment depression on electrocardiography and perfusion defects on tomographic thal-Hum-201 scintigraphy) was detected in 37 of 225 men (16%), versus 2 of 56 women (4%, p < 0.05). The prevalence of SI increased with age from 6% in men aged <55 years to 18% in men aged 55 to 70 years, and to 25% in men aged >70 years (p < 0.001). Compared with the 118 men with concordant normal exercise electrocardiogram and thallium scan (normals), men with SI were older (p < 0.001), and had a higher waist-to-hip ratio (p < 0.005), higher plasma triglyceride levels (p < 0.001), and lower high-density lipoprotein (HDL) cholesterol levels (p < 0.001). In stepwise logistic regression analysis, age, waist-to-hip ratio, and HDL levels were independent predictors of SI in men. Compared with 108 men with overt CAD, men with SI were younger (67 ± 2 vs 73 ± 1 years, p < 0.001) but had similar plasma lipids and waist-to-hip ratio. Thus, older age, male gender, abdominal obesity, and reduced HDL levels—all well-established risk factors for overt CAD—were risk factors for exercise-induced SI in these asymptomatic volunteers.

Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism.

The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of cholesterol in HDL and the subsequent transfer of cholesteryl ester towards apolipoprotein B-containing lipoproteins. Phospholipid transfer protein (PLTP) may be involved in the regulation of HDL particle size. We therefore measured the activities of LCAT, CETP and PLTP using exogenous substrate assays, as well as lipids, lipoproteins, insulin and C-peptide in fasting plasma from eight healthy obese men (body mass index > 27 kg m-2) and 24 non-obese subjects. The obese men had lower levels of HDL cholesterol (P < 0.05) and higher levels of plasma triglycerides (P < 0.05), insulin (P < 0.05) and C-peptide (P < 0.01), as compared to the quartile of subjects with the lowest body mass index (BMI < 22.4 kg m-2). CETP and PLTP activities were elevated in the obese men by 35% (P < 0.01) and by 15% (P < 0.05), respectively. LCAT activity was comparable among the quartiles. Linear regression analysis showed that CETP activity was positively correlated with body mass index (P < 0.02), fasting blood glucose (P < 0.05) and plasma C-peptide (P < 0.05). PLTP activity was positively related to body mass index (P < 0.01), waist to hip circumference ratio (P < 0.001), as well as to fasting blood glucose (P < 0.05) and plasma C-peptide (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired glucose and insulin metabolism in borderline hypertension.

This study investigated glucose and insulin metabolism in borderline hypertension (BHT) defined as repeated diastolic blood pressures (DBP) of 85-94 mmHg. Seventy-five BHT and 75 age-matched normotensive (NT, DBP < or = 80 mmHg) men were recruited from a population screening programme. Plasma lipoproteins were determined and an oral glucose tolerance test was performed (WHO criteria). Fasting insulin was significantly higher in the BHT group (17.2 vs 14.2 mU/ml, p < 0.001), whereas fasting blood glucose levels were similar in the two groups, indicating a reduced insulin sensitivity. The BHT group had significantly lower levels of HDL cholesterol and higher levels of plasma triglycerides, VLDL cholesterol and VLDL triglycerides. When adjusted for BMI these differences disappeared, whereas the basal insulin levels remained significantly elevated (F = 10.7, p < 0.001). These results indicate that an altered glucose and insulin metabolism is present already in the early stages of hypertension. They also suggest that these disturbances are only partly dependent on BMI. This supports the hypothesis that reduced insulin sensitivity could be of importance in the early phases of essential hypertension.

Meal composition affects postprandial fatty acid oxidation

Pages R1065–R1070: D. M. Surina, W. Langhans, R. Pauli, and C. Wenk. “Meal composition affects postprandial fatty acid oxidation.” Results from a similar experiment performed after this article went to press have led the authors to conclude that the β-hydroxybutyrate values reported in this article are unreliable. They are probably skewed by high plasma triglyceride levels. The authors deeply regret this error and request that the readers disregard the related interpretations.

Excess body weight. An underrecognized contributor to high blood cholesterol levels in white American men.

The influence of body weight on serum lipids is often overlooked in clinical practice. The association between body weight adjusted for height as calculated by body-mass index (BMI) and serum lipid and lipoprotein levels in white men was examined using the second National Health and Nutrition Examination Survey (NHANES II). Lipid results were categorized into six different levels of BMI: (1) 21.0 kg/m2 or lower, (2) 21.1 to 23.0 kg/m2, (3) 23.1 to 25.0 kg/m2, (4) 25.1 to 27.0 kg/m2, (5) 27.1 to 30.0 kg/m2, and (6) greater than 30.0 kg/m2, and three age groups: (1) young men (20 through 44 years), (2) middle-aged men (45 through 59 years), and (3) older men (60 through 74 years). Using linear trend analysis, changes in BMI from categories 2 to 5 in young men were associated with a total cholesterol level 0.59 mmol/L (23 mg/dL) higher (P < .01), a non-high-density lipoprotein (non-HDL) cholesterol level 0.70 mmol/L (27 mg/dL) higher (P < .01), and a low-density lipoprotein (LDL) cholesterol level 0.59 mmol/L (23 mg/dL) higher (P = .03). For middle-aged men and older men, the same change in BMI was associated with smaller but still significant differences in total cholesterol levels (higher by 0.31 mmol/L [12 mg/dL] [P < .01] and 0.28 mmol/L [11 mg/dL] [P < .01], respectively) and non-HDL cholesterol levels (higher by 0.37 mmol/L [14 mg/dL] [P < .01] and 0.25 mmol/L [10 mg/dL] [P < .01], respectively), whereas the LDL cholesterol levels were unchanged. Although advancing age may blunt the BMI-associated differences in total and LDL cholesterol levels, the BMI-associated differences in triglyceride levels (higher by 0.70 to 1.33 mmol/L [62 to 118 mg/dL] [P < .001]) and HDL cholesterol levels (lower by 0.18 to 0.39 mmol/L [7 to 15 mg/dL] [P < .001]) were of similar magnitude in all age groups. Excess body weight is associated with deleterious changes in the lipoprotein profile. Higher BMI was associated at all ages with higher plasma triglyceride level, lower HDL cholesterol level, and higher total and non-HDL cholesterol levels. In young men, the higher total cholesterol level was reflected mainly in the LDL cholesterol level; in middle-aged and older men, in the non-HDL fraction. Programs to reduce coronary heart disease by improving lipid levels should include more emphasis on achieving and maintaining ideal body weight.

Blood values of common cranes ( Grus grus) by age and season

1. 1. We studied the blood composition of common cranes ( Grus grus) along the wintering period (October–March). 2. 2. Plasma proteins decreased along the winter period whereas plasma urea increased. Both parameters were highly correlated. 3. 3. Plasma levels of uric acid, triglycerides and cholesterol did not change during the winter. Young birds showed higher levels of plasma triglycerides. 4. 4. Red blood cell number, hematocrit and blood hemoglobin content were similar in young and adult birds. Lower values of hematocrit and red cell number were recorded in early autumn. 5. 5. Total white blood cell number did not change during the winter, young birds showing higher numbers than adults. Lymphocyte number decreased from November to March while heterophil counts increased.