Low Cholesterol Group Research Articles

Are higher total serum cholesterol levels associated with better long-term motor function after ischemic stroke?

ObjectivesThe objective of the study was to investigate the prognostic role of total cholesterol (TC) level on the long-term motor function after ischemic stroke.MethodsOne hundred and fourteen patients with ischemic stroke were included and divided into high total cholesterol (HTC; TC ≧5.18 mmol/l or ≧200 mg/dl) and low total cholesterol (LTC; TC <5.18 mmol/l or <200 mg/dl) groups. The motor outcome was evaluated using the motor score of the Fugl–Meyer assessment (MFMA) at 2 weeks (baseline), 1, 3, 6, and 12 months after stroke. Prognostic factors on the repeated measurements of the MFMA were investigated using the linear mixed regression model.ResultsThe TC, basal ganglion lesion, baseline MFMA, first-time stroke, and follow-up time were identified as significant predictors for serial MFMA scores. The HTC group had higher MFMA scores than the LTC group by 2.72 units (95% confidence interval (CI): 0.17, 5.27, P = 0.037). An elevation of one unit of baseline MFMA led to a 0.86 increase (95% CI: 0.82, 0.90, P < 0.001) of subsequent MFMA scores. Subjects with basal ganglion lesions had lower MFMA scores by −3.55 (95% CI: −5.97, −1.14, P = 0.004).DiscussionHigher total cholesterol at the acute phase of ischemic stroke is a favorable prognostic factor for long-term motor function.

Serum High-Density Lipoprotein Cholesterol Levels as a Prognostic Indicator in Patients With Idiopathic Pulmonary Arterial Hypertension

High-density lipoprotein (HDL) cholesterol levels are a strong, independent inverse predictor of cardiovascular disease. The present study aimed to determine whether serum HDL cholesterol levels correlated with disease severity and clinical outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). The serum HDL cholesterol levels were measured in 76 Chinese patients with IPAH and 45 healthy controls, together with other clinical variables. Univariate and multivariate Cox proportional hazards analysis was performed to assess the prognostic value of HDL cholesterol and event-free survival. Event-free survival was estimated using the Kaplan-Meier method. Serum HDL cholesterol levels were significantly decreased in patients with IPAH compared with controls (1.0 ± 0.3 vs 1.5 ± 0.3 mmol/L; p <0.001). The serum HDL cholesterol levels decreased in proportion to the severity of World Health Organization functional class. Compared to the high HDL cholesterol group, the low HDL cholesterol group demonstrated a significantly lower 6-minute walking distance, cardiac index, mixed venous saturation, and arterial carbon dioxide pressure but significantly greater pulmonary vascular resistance and serum uric acid levels. The serum HDL cholesterol levels correlated positively with the cardiac index (r = 0.42; p = 0.002) and negatively with the pulmonary vascular resistance (r = -0.25; p = 0.04). Serum HDL cholesterol was independently related to event-free survival on multivariate Cox proportional hazards analysis. Kaplan-Meier survival curves according to the median HDL cholesterol value showed that lower HDL cholesterol levels were associated with lower event-free survival. In conclusion, serum HDL cholesterol levels might serve as an indicator of disease severity and prognosis in patients with IPAH.

Reductions in blood pressure with additional lipid-lowering treatment among hypertensive patients: results from China

BackgroundRecently several clinical studies have also shown that lipid-lowering drugs may exert a favourable effect on blood pressure. But to our knowledge there are no data showing the effect of...

Low cholesterol in dialysis patients--causal factor for mortality or an effect of confounding?

The association between cholesterol and mortality is reversed in end-stage renal disease (ESRD). This phenomenon has many potential explanations, one of them being 'time discrepancy of competing risks'. It states that hypercholesterolaemia is beneficial only in the short term, while it worsens survival over a long-term interval. It is also proposed that the reversed relationship between cholesterol and outcome is due to confounding protein-energy wasting. The aim of the study was to verify the hypothesis of time discrepancy of competing risks in 1191 incident dialysis patients (Netherlands Cooperative Study on the Adequacy of Dialysis). Conditional Cox proportional hazards analysis was applied, where associations between cholesterol level and short-term versus long-term mortality were being compared. Furthermore, to evaluate associations between cholesterol and outcome free from confounding, Mendelian randomization was introduced, using apolipoprotein E (apoE) genotype. Hypercholesterolaemia (>240 mg/dL) was associated with improved 5-year survival when compared to the low cholesterol group (<200 mg/dL), hazard ratio (HR) = 0.62 (0.47-0.82), P < 0.001. However, conditional Cox proportional hazards analysis revealed that the reverse association between high cholesterol and all-cause mortality was evident only during the first year of follow-up, HR = 0.43 (0.23-0.80), P < 0.01, and then, gradually, declined. The apoE genotype significantly affected cholesterol concentration. The ε2 carriers, associated with low cholesterol, had significantly increased risk of non-cardiovascular mortality. Reverse association between cholesterol concentration and mortality in dialysis patients is short-termed, consistent with the hypothesis of time discrepancy of competing risks. Low cholesterol appeared to affect non-cardiovascular mortality in ESRD patients free from confounders.

농촌지역 일부 성인이 섭취한 식품과 관련된 생리적 지수

본 연구는 농촌지역 성인의 주요 식품 섭취 빈도와 혈압, 비만도, 허리/둔부 둘레비, 콜레스테롤과의 관계를 분석하고자 G군 소재 890명(남성 438명, 여성 452명)명을 조사대상으로 식품섭취 빈도 및 생리적 지수에 대한 조사를 하였으며 그 결과는 다음과 같다. 본 연구대상자는 남자가 49.2%, 여자가 50.8% 이었고, 연령별로는 60세 이상이 39.7%이었다. 학력으로는 고졸 이상이 43.8%이었고, 결혼한 경우가 84.3%이었으며, 직업은 농업인 경우가 46.7% 이었다. 자신의 건강상태를 좋다고 인지한 경우는 31.9%이었고, 나쁘다고 인지한 경우는 21.9%이었다. 흡연자는 20.7%이었으며, 혈압상태는 고혈압전단계가 14.9%이었고, 고혈압인 경우가 12.1% 이었다. BMI는 25.0kg/<TEX>$m^2$</TEX>이상인 비만인 경우가 27.1%이었다. WHR은 남자인 경우는 0.90이상, 여자인 경우는 0.85이상으로 비만인 경우가 42.0%이었다. 콜레스테롤은 200mg/dl이하로 정상인 경우가 76.1%이었고, 201mg/dl를 넘는 경우가 23.9%이었다. 뇨당은 양성인 경우가 8.7%이었다. 연령을 보정하여 식품섭취 빈도와 생리적 지수와의 관계를 보면 혈압은 과일류(p=.003)를 자주섭취한 군이 혈압이 정상이었으며, BMI는 우유류(p=.045)를 자주 섭취한 군과 주류(p=.007)를 적게 섭취한 군이 BMI가 정상이었다. 허리/둔부 둘레비는 채소류(p=.046)와 우유류(p=.021)를 자주섭취한 군과 주류(p=.003)를 적게 섭취한 군이 정상이었고, 콜레스테롤은 곡류(p=.020), 두류(p=.039) 및 해조류(p=.007)를 자주 섭취한 군이 콜레스테롤 수치가 낮은 결과를 보였다. 이상의 연구결과를 종합하면 혈압은 과일류, BMI는 우유류와 주류, 허리/둔부 둘레비는 채소, 우유류 및 주류, 콜레스테롤은 곡류, 두류 및 해조류 섭취와 유의한 관련성을 보여 식생활 개선에 대한 인식을 높이고 개개인에게 맞춤식 건강 증진 사업을 전개해 나가는 것이 필요하다고 사료된다. Objectives: The objective of this study was to identify the association of food intake with bio-physiological indicators: blood pressure, body mass index (BMI), waist/hip ratio (WHR), cholesterol and urine sugar among rural people. Methods: The subjects were 890 inhabitants from 14 towns of G County in Honam province. Data were collected by interview and self-reported with structured questionnaires from April 6th to 30th 2005. Data were analyzed with the frequency, percentage, t-test, <TEX>$x^2$</TEX>-test, ANOVA, Scheffe test and ANCOVA using SPSS 12.0 program. Results: Pre-hypertensive and hypertensive group was 27.0%, overweight and obese 27.1%, more than 0.90 in WHR 42.0%, more than 201 mg/dl of cholesterol 23.9%, and positive urine sugar was 8.7% in general. Among eleven food groups, fruit intakes were more effective in normotensive group than in the others. Vegetables, liquors, and milk products were 0.90 WHR more effective than the others. Milk products and liquors in BMI, and grains, beans and seaweed in low cholesterol group were more effective than the others. Conclusions: Bio-physiological indicators are related significantly only with fruits, milk products, meats, cereal and liquors among eleven food categories. Further study on the relationship between food intake, physical activities, smoking, drinking and lifestyle with bio-physiological indicators are suggested.

Usefulness of Serum High-Density Lipoprotein Cholesterol Level as an Independent Predictor of One-Year Mortality After Percutaneous Coronary Interventions

Low levels of high-density lipoprotein (HDL) cholesterol are a marker of coronary artery disease progression and are associated with cardiovascular events. However, whether low HDL cholesterol is a useful prognostic indicator after percutaneous coronary intervention (PCI) is not known. In a sample of 4,088 patients who underwent PCI we evaluated 1-year mortality and repeat revascularization as a function of baseline HDL levels classified into approximate quartiles of very low (<35 mg/dl), low (35 to 40 mg/dl), medium (41 to 47 mg/dl) and high (48 to 120 mg/dl) HDL cholesterol. Decreasing levels of HDL cholesterol were associated with younger age, male gender, smoking, diabetes mellitus, and a history of bypass surgery (p <0.0001 for all). One-year mortality and coronary revascularization were significantly higher in the very low HDL cholesterol group compared with the other groups (very low HDL cholesterol 6.5% and 25.4%, respectively; low HDL cholesterol 3.1% and 20.8%; medium HDL cholesterol 4.3% and 22.7%; high HDL cholesterol 3.1% and 20.6%, p = 0.0001 and p = 0.007). One-year mortality was significantly higher in men with an HDL cholesterol level <33 mg/dL and in women with an HDL cholesterol level <38 mg/dL. In multivariable analysis, very low HDL was associated with nearly twofold the risk of death after adjusting for other independent predictors of outcome. In conclusion, in patients with coronary artery disease undergoing PCI, a baseline HDL cholesterol level <35 mg/dl is an important prognostic indicator. Baseline HDL cholesterol levels <33 mg/dl for men and <38 mg/dl were associated with higher one-year mortality after PCI.

Apolipoprotein E/intrauterine undernutrition interaction and hypercholesterolemia in children

The inconsistency of data regarding intrauterine programming of cardiovascular risk factors may be largely caused by genetic predisposition and later lifestyle. We analyzed whether low birth weight and apolipoprotein E (Apo E) polymorphism participate in the onset of hypercholesterolemia in children. Our approach was based on hypothesis that genetically enhanced susceptibility of different individuals might influence the effects of intrauterine programming. Two groups were selected from 2000 children at the beginning of an ongoing study: high-cholesterol group (HCG, n=67) and low-cholesterol group as a control (LCG, n=72). Both groups were divided into tertilles according to birth weight and we compared birth weight and apo E gene polymorphism between and within groups. The birth weight in HCG was 0.3 kg lower than the controls (p<0.001). The frequency of apoE4 was 31 % in HCG and only 10 % in LCG. The frequency of apoE4+ genotypes was not significantly different between tertilles based on birth weight in HCG. We suppose that intrauterine undernutrition, demonstrated by a lower birth weight, participates in the development of hypercholesterolemia already in childhood. The effects of low birth weight and the candidate gene - apoE, are synergic.

Cholesterol and suicide attempts: A prospective study of depressed inpatients

Low cholesterol levels have commonly been associated with various suicide measures. We sought to examine suicide attempts in a prospective sample of depressed patients that on prior analysis demonstrated an association between low cholesterol and subsequent suicide completions. Seventy-four inpatients with Research Diagnostic Criteria unipolar major depression, bipolar depression or schizoaffective depression entered a prospective follow-up study from 1978 to 1981. Kaplan–Meier survival analysis and Cox regression were utilized to elucidate the relationship between cholesterol levels and subsequent severe suicide attempts as well as all suicide attempts regardless of severity. Attempts preceding index hospitalization and other lifetime attempts were evaluated cross-sectionally. Low serum cholesterol levels did not predict subsequent suicide attempts. Contrary to our hypothesis, the high cholesterol group was associated with increased risk of suicide attempts on survival analysis in those less than median age. Nonetheless, in cross-sectional analysis, the low cholesterol group had more suicide attempts preceding index hospitalization and more remote lifetime attempts. The results from this prospective dataset do not support an association between low cholesterol and subsequent suicide attempts despite replicating the retrospective findings of previous case–control and cross-sectional studies.

Dual PPARα/γ Agonist Tesaglitazar Reduces Atherosclerosis in Insulin-Resistant and Hypercholesterolemic ApoE*3Leiden Mice

We investigated whether the dual PPARalpha/gamma agonist tesaglitazar has anti-atherogenic effects in ApoE*3Leiden mice with reduced insulin sensitivity. ApoE*3Leiden transgenic mice were fed a high-fat (HF) insulin-resistance-inducing diet. One group received a high-cholesterol (HC) supplement (1% wt/wt; HC group). A second group received the same HC supplement along with tesaglitazar (T) 0.5 micromol/kg diet (T group). A third (control) group received a low-cholesterol (LC) supplement (0.1% wt/wt; LC group). Tesaglitazar decreased plasma cholesterol by 20% compared with the HC group; cholesterol levels were similar in the T and LC groups. Compared with the HC group, tesaglitazar caused a 92% reduction in atherosclerosis, whereas a 56% reduction was seen in the cholesterol-matched LC group. Furthermore, tesaglitazar treatment significantly reduced lesion number beyond that expected from cholesterol lowering and induced a shift to less severe lesions. Concomitantly, tesaglitazar reduced macrophage-rich and collagen areas. In addition, tesaglitazar reduced inflammatory markers, including plasma SAA levels, the number of adhering monocytes, and nuclear factor kappaB-activity in the vessel wall. Tesaglitazar has anti-atherosclerotic effects in the mouse model that go beyond plasma cholesterol lowering, possibly caused by a combination of altered lipoprotein profiles and anti-inflammatory vascular effects.

Impact of Low High-Density Lipoproteins on In-Hospital Events and One-Year Clinical Outcomes in Patients With Non–ST-Elevation Myocardial Infarction Acute Coronary Syndrome Treated With Drug-Eluting Stent Implantation

High-density lipoprotein (HDL) cholesterol has protective cardiovascular effects. We investigated the effect of baseline HDL cholesterol on the outcomes of patients who underwent drug-eluting stent implantation for acute coronary syndrome. Since March 2003, 1,032 consecutive patients were, according to their baseline HDL cholesterol level, included in a low HDL cholesterol group (n = 550, <40 mg/dl in men, <45 mg/dl in women, mean 32 +/- 7) or a high HDL cholesterol group (n = 482, >40 mg/dl in men, >45 mg/dl in women, mean 55 +/- 19). End points were death, Q-wave myocardial infarction, target lesion revascularization, and a composite of major adverse cardiac events at 30 days and 1 year. We assessed the relation between HDL cholesterol and end points. Patients with low HDL cholesterol more often had diabetes, a higher body mass index, higher triglyceride levels, and lower total cholesterol levels. Low-density lipoprotein cholesterol and statin treatment (98% in the 2 groups) were comparable. Incidences of mortality and major adverse cardiac events at 30 days were higher in the low than in the high HDL cholesterol group (p <0.001 and p = 0.002, respectively; chi-square analysis). At 1 year, more deaths occurred in the low HDL cholesterol group (p <0.001; chi-square analysis), as did major adverse cardiac events (p <0.001; chi-square analysis). Multivariate analysis showed low HDL cholesterol at baseline (hazard ratio 2.61, 95% confidence interval 1.33 to 5.12) to be a key predictor of major adverse cardiac events and death (hazard ratio 3.33, 95% confidence interval 1.15 to 10.0) at 1 year. In conclusion, regardless of baseline low-density lipoprotein cholesterol levels and statin therapy, additional strategies to increase HDL cholesterol should be evaluated in patients with acute coronary syndrome.

Zinc Finger Protein 202, genetic variation, and HDL cholesterol in the general population

Zinc Finger Protein 202 (ZNF202) is a transcriptional repressor that binds elements found predominantly in genes involved in HDL metabolism. We tested the following hypotheses: 1) frequencies of single-nucleotide polymorphisms (SNPs) and haplotypes in ZNF202 differ between individuals with low and high HDL cholesterol; and 2) SNPs in ZNF202 affect HDL cholesterol levels in the general population. We screened the promoter and protein-coding exons of ZNF202 in individuals with the highest 1% (n = 95) and lowest 1% (n = 95) HDL cholesterol among 9,259 Danish adults. None of the 10 SNPs identified differed in frequency as single sites or as haplotypes between low and high HDL cholesterol groups. In accordance with this, seven mutations were equally frequent (4-5%) in individuals with low or high HDL cholesterol. Finally, for all five SNPs identified in the coding region, we determined the association of genotype with HDL cholesterol in 9,259 individuals from the general population. Four SNPs were not associated with variation in HDL cholesterol, although c.*2T>G homozygosity was associated with a discrete effect on HDL cholesterol in men. We show that genetic variation in ZNF202 is common in the general population. However, SNPs in the protein-coding region of ZNF202 do not make a major contribution to HDL cholesterol levels.

High Cholesterol Intake Modifies Chylomicron Metabolism in Normolipidemic Young Men

Whether the consumption of egg yolk, which has a very high cholesterol content without excess saturated fats, has deleterious effects on lipid metabolism is controversial. Absorbed dietary cholesterol enters the bloodstream as chylomicrons, but the effects of regular consumption of large amounts of cholesterol on the metabolism of this lipoprotein have not been explored even though the accumulation of chylomicron remnants is associated with coronary artery disease (CAD). We investigated the effects of high dietary cholesterol on chylomicron metabolism in normolipidemic, healthy young men. The plasma kinetics of a chylomicron-like emulsion, doubly-labeled with 14C-cholesteryl ester (14C-CE) and 3H-triolein (3H-TG) were assessed in 25 men (17-22 y old, BMI 24.1 +/- 3.4 kg/m2). One group (n = 13) consumed 174 +/- 41 mg cholesterol/d and no egg yolk. The other group (n = 12) consumed 3 whole eggs/d for a total cholesterol intake of 804 +/- 40 mg/d. The nutritional composition of diets was the same for both groups, including total lipids and saturated fat, which comprised 25 and 7%, respectively, of energy intake. Serum LDL and HDL cholesterol and apoprotein B concentrations were higher in the group consuming the high-cholesterol diet (P < 0.05), but serum triacylglycerol, apo AI, and lipoprotein (a) did not differ between the 2 groups. The fractional clearance rate (FCR) of the 14C-CE emulsion, obtained by compartmental analysis, was 52% slower in the high-cholesterol than in the low-cholesterol group (P < 0.001); the 3H-TG FCR did not differ between the groups. Finally, we concluded that high cholesterol intakes increase the residence time of chylomicron remnants, as indicated by the 14C-CE kinetics, which may have undesirable effects related to the development of CAD.

Effects of simvastatin on NF-κB-DNA binding activity and monocyte chemoattractant protein-1 expression in a rabbit model of atherosclerosis

To observe the effects of simvastatin on nuclear factor kappaB (NF-kappaB)-DNA binding activity and on the expression of monocyte chemoattractant protein-1 (MCP-1) in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group (LC), high-cholesterol group (HC), high-cholesterol+simvastatin group (HC+S) and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shiftassay (EMSA), immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kappaB-DNA binding activity, MCP-1 protein expression, intima thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kappaB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC+S groups were significantly lower than those in the HC group (P<0.05). There was no significant difference in the serum lipids between the LC and HC+S groups (P>0.05), but the NF-kappaB-DNA binding activity, the expression of MCP-1 protein and the intima thickness and plaque area of aorta in the HC+S group were significantly decreased as compared to the LC group (P<0.05). This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kappaB-DNA binding activity and by reducing the expression of MCP-1 protein.

Effect of dietary supplementation with glucomannan on plasma total cholesterol and low density lipoprotein cholesterol in hypercholesterolemic children

This paper evaluates the effect of the adjunct of the hydrosoluble fiber glucomannan to a Step-One-Diet in 40 plasma hypercholesterolemic children, during a randomized controlled trial, to reduce plasma cholesterol. All the subjects recruited underwent an 8-week run in diet period; a Step-One-Diet was prescribed. After that, they were randomly allocated to one of two groups: Step-One-Diet only (control), and Step-One-Diet plus glucomannan in gelatine capsules. After another 8 weeks of treatment, the results were compared within and between the two groups. Glucomannan treated group showed decreased values in plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) vs. control group after 8 weeks of treatment. The percentage decrease showed a statistically significant difference between sex groups. Decreases were observed in favor of female vs. male children in TC (24% vs. 9%) and LDL-C (30% vs. 9%). These results suggest that glucomannan may represent a rationale adjunct to diet therapy in primary prevention in high risk hypercholesterolemic children.

Application of pooled genotyping to scan candidate regions for association with HDL cholesterol levels

Association studies are used to identify genetic determinants of complex human traits of medical interest. With the large number of validated single nucleotide polymorphisms (SNPs) currently available, two limiting factors in association studies are genotyping capability and costs. Pooled DNA genotyping has been proposed as an efficient means of screening SNPs for allele frequency differences in case-control studies and for prioritising them for subsequent individual genotyping analysis. Here, we apply quantitative pooled genotyping followed by individual genotyping and replication to identify associations with human serum high-density lipoprotein (HDL) cholesterol levels. The DNA from individuals with low and high HDL cholesterol levels was pooled separately, each pool was amplified by polymerase chain reaction in triplicate and each amplified product was separately hybridised to a high-density oligonucleotide array. Allele frequency differences between case and control groups with low and high HDL cholesterol levels were estimated for 7,283 SNPs distributed across 71 candidate gene regions spanning a total of 17.1 megabases. A novel method was developed to take advantage of independently derived haplotype map information to improve the pooled estimates of allele frequency differences. A subset of SNPs with the largest estimated allele frequency differences between low and high HDL cholesterol groups was chosen for individual genotyping in the study population, as well as in a separate replication population. Four SNPs in a single haplotype block within the cholesteryl ester transfer protein (CETP) gene interval were significantly associated with HDL cholesterol levels in both populations. Our study is among the first to demonstrate the application of pooled genotyping followed by confirmation with individual genotyping to identify genetic determinants of a complex trait.

Apolipoprotein B as a Marker of Familial Hyperlipoproteinemia

Families with 10-12-year-old schoolchildren were informed about and asked to participate in a study to identify children with hyperlipoproteinemia. We hypothesised that children and families with familial blood lipid abnormalities, specifically those with familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCHL), could be identified by the child's apolipoprotein B level exceeding the 95th percentile. Written information and consent was distributed to the families. Families whose child had an apoB concentration exceeding the 95th percentile were further examined. Children and parents were divided into normal, high and very high low density lipoprotein cholesterol (LDLC) groups. In adults a high LDLC level was defined as > 4.1-4.9, a very high as > 4.9 mmol/l, in children as > 3.4-4.1 and > 4.1 mmol/l, respectively. The triglyceride level was regarded as high when > 3.6 mmol/l. Of 2,855 families, 2,186 agreed to participate. The 95th percentile apoB level was for boys 0.98 and girls 1.07 g/l. Of the 131 children with an apoB level above the 95th percentile, 109 families accepted further examinations. Of 109 hyperapoB children 23 were obese. Normal LDLC was found in 28 hyperapo B children of whom six parents had high/very high LDLC and one high triglyceride concentrations. A high LDLC level was found in 52 children of whom 23 parents had higy/very high LDLC and another five high LDLC and/or high triglyceride concentrations. A very high LDLC level was found in 29 children, in two of them due to hypothyroidism, 17 had a parent with high/very high LDLC and another two parents a high triglyceride concentration. Familial hypercholesterolemia, defined as a LDLC concentration above twice the normal one in the child and a very high level in a parent, was suspected in six families, five having a relative with premature CHD. The families with FCHL should be included in the 20 families with hyperapoB and a child with high-very high LDLC and a parent with very high LDLC or TG levels. Of the 109 children examined due to the child's increased apoB concentration, about 20% were obese and 75% had an increased LDLC concentration. A familial occurrence of hyperlipoproteinemia was evident in about 50% of the families with an hyperapoB child. Six families probably suffer from familial hypercholesterolemia. The definite number of FCHL families could not be defined since extended pedigrees were not available. A high suspicion of FCHL was evident in 20 families. ApoB is an important marker of hyperlipoproteinemia of familial occurrence identifying families in need of primary CHD prevention.

Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE*3-Leiden transgenic mice: evidence for antiinflammatory effects of rosuvastatin.

Statins can exert anti-inflammatory antiatherosclerotic effects through an anti-inflammatory action, independent of lowering cholesterol. We addressed the question whether the anti-inflammatory activities of statins can reduce atherosclerosis beyond the reduction achieved by cholesterol lowering per se. Two groups of 20 female APOE*3-Leiden mice received either a high-cholesterol diet (HC) or a high-cholesterol diet supplemented with 0.005% (wt/wt) rosuvastatin (HC+R). The HC diet alone resulted in a plasma cholesterol concentration of 18.9+/-1.4 mmol/L, and administration of rosuvastatin lowered plasma cholesterol to 14.1+/-0.7 mmol/L. In a separate low-cholesterol (LC) control group, the dietary cholesterol intake was reduced, which resulted in plasma cholesterol levels that were comparable to the HC+R group (13.4+/-0.8 mmol/L). Atherosclerosis in the aortic root area was quantified after 24 weeks. As compared with the HC group, the LC group had a 62% (P<0.001) reduction in cross-sectional lesion area. When compared with the LC group, the HC+R group showed a further decrease in cross-sectional lesion area (80%, P<0.001), size of individual lesions (63%, P<0.05), lesion number (58%, P<0.001), monocyte adherence (24%, P<0.05), and macrophage-containing area (60%, P<0.001). Furthermore, rosuvastatin specifically suppressed the expression of the inflammation parameters MCP-1 and TNF-alpha in the vessel wall and lowered plasma concentrations of serum amyloid A and fibrinogen, independent of its cholesterol-lowering effect. Rosuvastatin reduces atherosclerosis beyond and independent of the reduction achieved by cholesterol lowering alone. This additional beneficial effect of rosuvastatin may be explained, at least partly, by its anti-inflammatory activity.

Dietary fat source and cholesterol interactions alter plasma lipids and tissue susceptibility to oxidation in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats.

Due to the potential for dietary fat source to alter plasma lipids and tissue antioxidant status, we hypothesized that blends of saturated, n-6 and n-3 fats with cholesterol would affect LDL and tissue susceptibility to in vitro oxidation. The effects of dietary fat blends of butter (B), beef tallow (T), soybean oil (SBO) or menhaden oil (MO) and cholesterol on systolic blood pressure (SBP), plasma lipoproteins and tissue susceptibility to glutathione (GSH) depletion and lipid peroxidation (TBARS) were examined in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. SBP in SHRs was higher (p < 0.001) than in WKYs at 13-weeks of age but was not altered by dietary fat or cholesterol. LDL- and HDL-cholesterol were greater (p < 0.001) in WKY than SHR. LDL-cholesterol and (VLDL- + LDL-cholesterol)/HDL-cholesterol ratios were reduced in MO vs. B, T and SBO groups. HDL-cholesterol levels tended to be lower and greater in B and MO groups, respectively vs. T and SBO groups. Initial LDL fluorescence was greater (p < 0.001) in high- vs. low-cholesterol groups. The change in LDL fluorescence was reduced (p < 0.001) in high-cholesterol groups, and MO vs. B, T and SBO rats. MO fed rats had reduced (p < 0.001) RBC, heart and liver GSH depletion and reduced (p < 0.01) tissue TBARS and RBC MDA production. In summary, a moderate level of dietary MO did not increase tissue and LDL in vitro oxidizability in SHR and WKY rats. High dietary cholesterol exhibited a protective effect against in vitro oxidation of LDL and selected tissues.

Relationship of hypolipidemia to cytokine concentrations and outcomes in critically ill surgical patients.

To determine the relationship of hypolipidemia to cytokine concentrations and clinical outcomes in critically ill surgical patients. Consecutive, prospective case series. Surgical intensive care unit of an urban university hospital. Subjects were 111 patients with a variety of critical illnesses, for whom serum lipid, lipoprotein, and cytokine concentrations were determined within 24 hrs of admission to a surgical intensive care unit. Controls were 32 healthy men and women for whom serum lipid, lipoprotein, and cytokine concentrations were determined. Blood samples were drawn on admission to the intensive care unit. Predetermined clinical outcomes including death, infection subsequent to intensive care unit admission, length of intensive care unit stay, and magnitude of organ dysfunction were monitored prospectively. Measurements included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoproteins A-I and B, phospholipid, triglyceride, interleukin-6, interleukin-10, soluble interleukin-2 receptor, tumor necrosis factor-alpha, and soluble tumor necrosis factor receptors p55 and p75. Mean serum lipid concentrations were extremely low: total cholesterol, 127 +/- 52 mg/dL; low-density lipoprotein cholesterol, 75 +/- 41 mg/dL; high-density lipoprotein cholesterol, 29 +/- 15 mg/dL. Total, low-density lipoprotein, and high-density lipoprotein cholesterol concentrations and apolipoprotein concentrations inversely correlated with interleukin-6, soluble interleukin-2 receptor, and interleukin-10 concentrations, whereas the triglyceride concentration correlated positively with tumor necrosis factor soluble receptors p55 and p75. Clinical outcomes were related to whether the admission cholesterol concentration was above (n = 56) or below (n = 55) the median concentration of 120 mg/dL. Each of the clinical end points occurred between 1.9- and 3.5-fold more frequently in the very low cholesterol (<120 mg/dL) group. Nine patients (8%) died during the hospitalization. Seven of the nine patients who died had total cholesterol concentrations below the median concentration of 120 mg/dL. Low cholesterol and lipoprotein concentrations found in critically ill surgical patients correlate with interleukin-6, soluble interleukin-2 receptor, and interleukin-10 concentrations and predict clinical outcomes.

Plasma cholesterol: an influencing factor in red blood cell oxygen release and cellular oxygen availability

Background: A fairly immediate reduction in angina pectoris symptoms after cholesterol lowering has been described. Our previous findings in rabbits and in a four-patient human pilot study indicated the existence of an RBC membrane barrier to oxygen (O 2) transport in the presence of hypercholesterolemia. Our current objective was to determine whether, and to what extent, the plasma cholesterol concentration is an influencing factor in RBC O 2 release and cellular O 2 availability. Study Design: In an unique O 2 diffusion analysis system, blood samples from 100 patients referred for lipid modification were analyzed. After 1 to 2 minutes of mixing in our diffusion analysis system, the next 1 to 2 minutes of circulation is comparable with 1 to 2 seconds of myocardial capillary flow. RBC O 2 diffusion was defined by the depletion rate of total O 2 content in blood from full O 2 saturation (98%) to desaturation (approximately 60%). Relative tissue O 2 availability was defined as the percentage decrease in O 2 availability between the high-cholesterol group and the low-cholesterol group. Results: The 100 patients were divided almost equally into two groups on the basis of plasma cholesterol ranges of 175 to 229 mg/dL (n = 49) and 230 to 299 mg/dL (n = 51). The mean cholesterol concentrations and percentage increases in the high-cholesterol group over the low-cholesterol group were: for plasma, 206 ± 0.3 and 256 ± 0.4 mg/dL, 24.3% (p < 0.001); for RBCs, 93 ± 0.2 and 106 ± 0.2 mg/dL, 14.0% (p < 0.001); and for RBC membranes, 41 ± 0.1 and 54 ± 0.2 mg/dL, 31.7% (p < 0.001). The blood O 2 diffusion curves were distinctly different between the high- and the low-cholesterol groups (p < 0.05). Blood O 2 diffusion, defined by the blood O 2 diffusion curves, was inversely proportional to the plasma, RBC, and RBC-membrane cholesterol concentrations. The relative tissue O 2 availability, after a circulation period of more than 3 minutes in the diffusion system, showed a decrease of 17.5% (p < 0.05) between the plasma cholesterol groups. In comparing the two plasma cholesterol concentration extremes of less than 200 mg/dL (n = 14) and greater than 275 mg/dL (n = 11) after a circulation period of more than 3 minutes in the diffusion system, we found a decrease in relative tissue O 2 availability of 35.8% (p < 0.05). Conclusions: The plasma cholesterol concentration may be an influencing factor in RBC-membrane cholesterol content, which, in turn, may regulate RBC-membrane O 2 transport, RBC O 2 release, and cellular O 2 availability. The implications of this work include the addition of angina pectoris control to the indications for appropriate lipid modification and the development of an in vitro blood stress test to replace patient cardiac stress testing.