Lower Total Cholesterol Concentrations Research Articles

Plasma oxysterols in normal and cholestatic children as indicators of the two pathways of bile acid synthesis

Background No information is available on the hepatic and extrahepatic pathways of bile acid synthesis in normal children and in pediatric cholestatic liver diseases. Methods To explore the changes of the two pathways of bile acid synthesis during development, plasma concentrations of 7α-hydroxycholesterol and 27-hydroxycholesterol were measured in 50 healthy children (1 month–14 years) and compared to 18 adult controls. We also measured plasma oxysterols in 31 patients with pediatric cholestatic liver disease. Results A progressive increase of plasma concentrations of both 27-hydroxycholesterol and 7α-hydroxycholesterol was found with age. In children with cystic fibrosis-associated liver disease plasma concentrations of 27-hydroxycholesterol were significantly lower compared to age-matched controls (5.6 ± 0.5 vs. 12.8 ± 1.1 μg/dl; p < 0.001) and paralleled significantly lower concentrations of total cholesterol. In infants with biliary atresia plasma concentrations of 27-hydroxycholesterol were significantly higher compared to age-matched controls (8.8 ± 0.8 vs. 4.4 ± 0.6 μg/dl, p < 0.001) paralleling significantly higher concentrations of total cholesterol while 7α-hydroxycholesterol resulted significantly lower (1.2 ± 0.2 vs. 2.3 ± 0.3 μg/100 mg of total cholesterol; p = 0.011). Conclusions Our data suggest that both pathways of bile acid synthesis reach a state of maturity only after the age of 4 years and are significantly influenced also in children by liver function and intestinal absorption of cholesterol.

The role of statins in heart failure

HMG CoA reductase inhibitors (statins) have an established place in the treatment of coronary artery disease. However, their role in the treatment of heart failure (HF), including HF due to coronary artery disease, has been controversial since beneficial as well as possible harmful effects may occur. Several recent studies lend support for a beneficial effect of the statins in HF. These include: (i) post hoc subgroup analyses of prospective randomized clinical trials of statin therapy among patients with stable coronary artery disease where statins reduce the incidence of new HF; (ii) subgroup analysis of the evidence of statin use in large HF trails with different medication and medical devices; (iii) retrospective observational studies of statin use in HF; and (iv) prospective randomized clinical trials of statins in non-ischemic. Beneficial effects include attenuation of cardiac hypertrophy, improvement in endothelial function, anti-inflammatory effects, reduction in the activity of matrix metalloproteinases, reduction in apoptosis, interference with neurohormones, and improved homeostasis. However, there are also theoretical concerns about statins in HF, and existing literature for their safety and efficacy in HF patients has been limited by the retrospective or observational nature of these analyses, examination of incompletely validated surrogate endpoints and small prospective studies in subgroups of HF subjects. In contrast with the normal population, low concentrations of LDL and total cholesterol are associated with a worse prognosis in HF patients and a possible mechanism is reduction in ubiquinone (coenzyme Q10) levels, which is required for oxidative phosphorylation in cells. The safety aspect of these drugs in HF patients needs to be answered before statins can be recommended as a routine drug. For the moment there are several large-scale prospective outcome studies in HF which probably will give us more definitive answers.

Effects of a clinoptilolite supplement in pig diets on performance and serum parameters

The effects of clinoptilolite in pig&amp;sbqua;s diets were examined on sixty Landrace &amp;times; Yorkshire crossbred pigs of both sexes divided into two groups: 1. control group, with basal diets; 2. treatment, with basal diets supplemented with 5 g clinoptilolite per 1 kg diet (Cp group). Feed and water were available &lt;i&gt;ad libitum&lt;/i&gt;. Individual live weights were recorded on days 45, 90 and 135 of the experiment. Feed consumptions were recorded weekly. Blood was drawn from the anterior vena cava of each pig at day 135 for the determination of serum biochemical parameters. During the first 90 days of the experiment pigs from the Cp group had higher body weight gain (BWG) compared with the control group (+2.5% and +7.0%, respectively) but in the finishing phase of growing their growth parameters were significantly lower (&amp;minus;4.8%). Blood serum biochemical parameters from all experimental pigs were generally within the normal range. Higher triglyceride concentration, lower total cholesterol concentration and increased activity of AST were recorded in the serum of the Cp group.

Dietetic and hypocholesterolaemic action of black soy peptide in dietary obese rats

AbstractTo investigate the effect of peptides from black soy (rat's eye) bean (Rhynchosia volubilis Lour.) on weight gain and lipid composition, Sprague–Dawley male rats were fed either a black soy peptide (BSP; 2, 6 or 10% of energy)‐containing diet or a casein control diet (20% of energy) enriched with 36% fat and 1% cholesterol for 28 days. Compared with the casein group, the BSP groups showed significant attenuation of body, liver and epididymal adipose tissue weight gains (P &lt; 0.05). Moreover, rats that consumed BSP had a lower total cholesterol concentration and low‐density lipoprotein/high‐density lipoprotein (LDL/HDL) ratio in serum and a lower level of hepatic triglycerides as well as higher excretion of faeces compared with those fed only casein (P &lt; 0.05). Molecular weights of peptides from black soy were mainly below 10 kDa, and Arg/Lys and Gly/Met ratios in BSP were five and three times of those in casein respectively. It is concluded that BSP can be a potent nutraceutical component for anti‐obesity and hypolipidaemic benefits. Copyright © 2007 Society of Chemical Industry

Effect of oral magnesium sulfate administration on blood pressure and lipid profile in streptozocin diabetic rat

Approximately one-third of patients with type 1 diabetes develop a variety of complications as a result of mechanisms that are not completely understood. However, insufficient metabolic control seems to play a major role. Other factors such as magnesium (Mg) could also be of importance. We designed this study to elucidate the effect of oral magnesium administration on plasma lipid profile and mesenteric fat in male Wistar rats. Animals were divided into 4 groups ( n = 10 in each group): one group served as control, while the other groups were made diabetic with a single i.v. injection of 40 mg/kg streptozocin. Animals in which the diabetic state lasted for 10 days were referred as acute diabetic rats, whereas those in which the diabetes lasted for 8 weeks were defined as chronic diabetics. Mg-treated chronic diabetic received 10 g/l of MgSO 4 added to the drinking water (0.46 g/24 h) for eight weeks following which the left common carotid artery was cannulated for continuous recording of blood pressure. Blood glucose, magnesium and lipid profiles levels were also determined. Diabetes induction caused plasma glucose, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), total cholesterol and triglyceride concentrations to increase, however plasma Mg level was decreased. Administration of MgSO 4 for eight weeks caused the return of the above factors to their normal levels. Mg concentrations also increased but failed to reach normal levels. Diabetes induction caused mesenteric fat/body weight ratio to increase, but administration of MgSO 4 reduced the ratio to normal levels. In addition, Mg administration returned systolic blood pressure to the normal level. Our results support the hypothesis that Mg may play a part in the management of diabetes and the prevention of its vascular complications in streptozocin-induced diabetic rats and it may be useful in the treatment of hyperlipidaemia in diabetic case.

Serum total cholesterol, HDL-C and LDL-C concentrations significantly correlate with the radiological extent of disease and the degree of smear positivity in patients with pulmonary tuberculosis

Background: Low serum total cholesterol (TC) concentrations in patients with pulmonary tuberculosis (PTB) have been demonstrated. It was shown that a cholesterol-rich diet might accelerate the sterilization rate of sputum cultures in PTB patients. It is known that smear positivity might be related to the radiological extent of disease (RED) in PTB patients. Objective: We hypothesized that there might be a relationship between initial serum TC concentrations; the degree of RED (DRED) and the degree of smear positivity (DSP) in PTB patients. Method: Eighty-three PTB patients and 39 healthy controls were included in the study. Serum TC, TG, HDL-C, VLDL-C and LDL-C concentrations were determined in all subjects. PTB patients were classified for their chest X-ray findings as minimal/mild, moderate and advanced. Correlations between serum lipid concentrations, DRED and DSP (0, 1+, 2+, 3+, 4+) were investigated. PTB patients and controls were also compared for serum lipid concentrations. Results: Significant differences between PTB patients and controls were detected for serum TC, HDL-C and LDL-C concentrations. On stepwise logistic regression analysis, DRED was found as one of the significant independent predictors of serum TC levels. We also found significant correlations between DRED and serum HDL-C concentrations ( r = − 0.60, p = 0.0001) and between DRED and serum LDL-C concentrations ( r = − 0.28, p = 0.011). There were also significant correlations between DSP and serum lipid concentrations. Conclusion: Our study suggests that serum TC, HDL-C and LDL-C concentrations are generally lower in patients with PTB than those in healthy controls. In addition, changes in these parameters might be related to DRED and DSP in PTB patients.

Possible connections among job stress, depressive symptoms, lipid modulation and antioxidants

Background Oxidative/antioxidative status may be related to psychological stress or pathogenesis of depression. Subjects and methods Participants were selected from 381 female nurses working in a university hospital, and the Brief Job Stress Questionnaire was utilized to assess them. Nurses with high job stress (JS) ( n = 18) and with low JS ( n = 15) consented to participate in this study. Depressive symptoms were assessed by the Centre for Epidemiologic Studies Depression scale (CES-D). Cholesterols, lipid peroxidation (malondialdehyde, MDA) and antioxidants in the plasma were measured. Results High JS participants exhibited significantly higher CES-D scores ( t = 3.34, p < 0.005), and significantly lower concentrations of total cholesterol (TC), low density + very low density lipoprotein cholesterols (LDL + VLDL), α-tocopherol, and β-carotene compared with low JS participants ( t = 2.69, p < 0.05; t = 3.46, p < 0.005; t = 2.96, p < 0.05; t = 2.98, p < 0.05, respectively). However, the reductions in plasma indicators were substantially weakened after controlling for lifestyle factors with the exception of LDL + VLDL and α-tocopherol. In addition, the significance of α-tocopherol concentrations appeared to depend on cholesterol levels. CES-D scores correlated positively with plasma MDA levels, the MDA / TC ratio and the MDA / LDL + VLDL ratio among the low JS group ( r = 0.69, p < 0.001; r = 0.79, p < 0.001; r = 0.75, p < 0.005, respectively), whereas there were no correlations among the high JS group. After controlling for lifestyle covariates, the relationship between CES-D scores and the MDA / LDL + VLDL ratio remained significant ( β = 0.95, p < 0.05) using a multiple linear regression model ( F = 3.61, p < 0.05). Limitations Sample numbers in each JS group were relatively small. Conclusions Psychological stress may reduce the plasma levels of LDL + VLDL accompanying an α-tocopherol decrease. There appeared to be a correlation between elevated MDA and depressive symptoms in low JS participants.

High levels of C‐reactive protein with low total cholesterol concentrations additively predict all‐cause mortality in patients with coronary artery disease

This study aimed to investigate independent and additive predictive effects of raised C-reactive protein (CRP) levels and decreased total cholesterol levels on mortality in patients with chronic coronary artery disease (CAD). Low total cholesterol (TC) levels are associated with worsened survival in chronic and acute diseases. Elevated CRP level is an important predictor of vascular events and mortality in patients with CAD. Potential inhibition of immune activation by circulating lipoproteins could be a link between cholesterol and inflammatory markers. A group of 387 patients (median age 59 years) with CAD and with or without severe heart failure (HF) were followed for a median of 5.06 years. Serum total cholesterol and CRP concentrations were measured at enrollment. The relationship between lipoproteins, CRP and survival was explored. High CRP concentrations were in significant association with severity of HF and predicted worsened survival in patients with CAD (hazard ratio 5.214, 95% CI 1.762-15.427). The association between CRP levels and mortality was independent of potential confounding factors such as age, body-mass index, severity of HF, smoking habits, hypertension and TC levels. The prediction of mortality by low TC levels was significant (hazard ratio 2.932, 95% CI 1.021-8.422). Furthermore, patients with increased CRP and decreased TC (additive predictive effect) phenotype had 11.714-times higher risk (95% CI 2.619-52.385) of being nonsurvivors than patients with low CRP/high TC. High CRP levels and low TC concentrations are independent and additive predictors of mortality in patients with CAD. Our data indicate that joint analysis of circulating lipoproteins and inflammatory biomarkers may improve prediction of survival in patients with CAD.

Safety and efficacy of atorvastatin in patients with severe renal dysfunction

To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. The follow-up period was a mean of 20+/-14.4 months (range 1-36 months) for those on atorvastatin versus 22+/-12.7 months (range 0.5-36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; -23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; -35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1-30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

The Association Between Cholesterol and Mortality in Heart Failure Comparison Between Patients With and Without Coronary Artery Disease

Hypercholesterolemia is a risk factor for development of coronary artery disease (CAD), however, several reports have suggested that low serum cholesterol is associated with a worse prognosis in patients with congestive heart failure (CHF). The objective of this study was to determine the prognostic value of cholesterol for CHF. The study subjects consisted of 133 consecutive patients hospitalized in our institution for progressive heart failure from April 2000 to March 2003. Thirty-two percent of the patients had CAD. After improvement of congestive heart failure and discharge from the hospital, lipid profiles, including serum total cholesterol (TC), triglycerides, and high and low density lipoprotein cholesterol (HDL, LDL, respectively), were obtained. During the follow-up period (2.3 +/- 0.9 years), 21 patients died. There was a significant difference between survivors and nonsurvivors in HDL (53 +/- 15, 43 +/- 15 mg/dL, P = 0.01), but no differences were observed in other variables. In patients with CAD, survivors had significantly lower TC concentrations (179 +/- 30 versus 246 +/- 55 mg/dL, P = 0.004), although in patients without CAD, survivors had significantly higher TC concentrations (203 +/- 37 versus 170 +/- 40 mg/dL, P = 0.02). Multivariate analysis showed high TC predicted a worse outcome in patients with CAD (odds ratio (OR) = 1.052, 95% confidence interval (CI) 1.002-1.104, P = 0.04), but a better outcome in patients without CAD (OR = 0.972, 95% CI 0.948-0.997, P = 0.03), independent of age, gender, medication, and complications. Thus, low serum cholesterol is associated with an improved outcome in patients with CAD, while it predicts a worse outcome in patients without CAD.

Effects of a dietary oxidized fat on cholesterol in plasma and lipoproteins and the susceptibility of low-density lipoproteins to lipid peroxidation in guinea pigs fed diets with different concentrations of vitamins E and C.

To investigate the effect of a dietary oxidized fat on the concentrations of cholesterol in liver, plasma, and lipoproteins and the susceptibility of low-density lipoproteins (LDL) to lipid peroxidation, and to explore the effects of vitamins E and C, male guinea pigs were divided into five groups. Four groups were fed diets with an oxidized fat supplemented with 35 or 175 mg alpha-tocopherol equivalents/kg and 300 or 1000 mg of vitamin C/kg for 29 days. One group, used as a control, was fed the same basal diet with fresh fat with 35 mg alpha-tocopherol equivalents/kg and 300 mg of vitamin C/kg. Guinea pigs fed the oxidized-fat diets, irrespective of dietary vitamin E and C concentrations, had significantly lower concentrations of total cholesterol in the liver and a lower concentration of cholesterol in LDL than the control animals fed the fresh fat. According to the lag time before onset of lipid peroxidation, LDL of guinea pigs fed the oxidized-fat diet with 35 mg alpha-tocopherol equivalents and 300 mg vitamin C/kg were significantly more susceptible to copper-induced lipid peroxidation than those of guinea pigs fed the fresh fat diet. Within the groups fed the oxidized fat diets, increasing the dietary vitamin E concentration from 35 to 175 mg/kg significantly (p < 0.05) and increasing the dietary vitamin C concentration from 300 to 1000 mg/kg in tendency (p < 0.10) reduced the susceptibility of LDL to oxidation. LDL of guinea pigs fed the oxidized fat diets with 175 mg alpha-tocopherol equivalents/kg were even more resistant to oxidation than LDL of guinea pigs fed the fresh diet. In conclusion, the study shows that dietary oxidized fat influences the cholesterol metabolism and the susceptibility of LDL to lipid peroxidation; the latter can be modified by dietary vitamins E and C.

Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients

Background:Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO). Methods:The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition. Results:A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 ± 14.5 years (mean ± SD), who had undergone dialysis for 36.3 ± 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 ± 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 ± 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-α, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment. Conclusion:The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.

Cardiovascular News

Cardiovascular News

Serum lipid levels and violence among Finnish male forensic psychiatric patients

Low total serum cholesterol (TC) concentrations have been found to be linked with suicidal and violent behaviours among psychiatric patients, and also in the general population. The connections between violence and other serum lipids, i.e. high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) and triglycerides (TG), are still controversial. It also remains unclear if these connections are non-linear. Would it be possible to determine a cut-off for HDL, LDL and TG levels, differentiating between suicidal or violent individuals and non-suicidal and non-violent individuals? A total of 385 Finnish forensic male patients was studied by using ROC-analysis, to clarify the optimal cut-off points for HDL, LDL and TG levels differentiating between secluded and non-secluded patients. Reasons for seclusions were acts that included suicidal and violent behaviours. Moderate sensitivities and specificities were achieved in the ROC-analyses concerning involuntary seclusions, particularly seclusions due to suicidal and/or violent behaviours. Here, the cut-off points for differentiating the secluded patients from the non-secluded ones were 1.16 mmol/l for HDL, 3.30 mmol/l for LDL and 1.40 mmol/l for TG. A high HDL level and low LDL and TG levels seem to be linked with an increased risk of impulsive suicidal and violent behaviour among Finnish forensic male patients.

Seclusion treatment measures and serum cholesterol levels among Finnish male forensic psychiatric patients

Low total serum cholesterol (TC) concentrations have been found to be linked with violent and suicidal behavior among mentally ill patients and also in the general population. However, it has remained unclear if this correlation is non-linear, which would allow the determination of a cutoff TC level to differentiate violent or suicidal subjects from non-violent and non-suicidal subjects. We studied, in 397 Finnish forensic male patients, by using ROC analysis, the optimal cut-off point for TC level to differentiate between those who had been secluded because of acute acts, including violent and suicidal behaviors, and those who had not. According to ROC analysis, the observed cut-off points of the TC levels (5.3 mmol/l) for differentiating between those patients that had been secluded and those that were nonsecluded were below the mean TC levels of the Finnish general male population, and moderate sensitivities and specificities were achieved. The low (below 5.3 mmol/l) TC level seems to be a marker for an increased risk of violent and suicidal behavior among Finnish forensic male patients.

Lipoprotein metabolism in Japanese centenarians: effects of apolipoprotein E polymorphism and nutritional status.

To assess the complex interaction of apolipoprotein (apo) E polymorphisms and environmental factors on lipoprotein profile in centenarians. Cross-sectional analysis. Tokyo metropolitan area. Seventy-five centenarians and 73 healthy older volunteers (mean age 63.1 +/- 10.0) living in the Tokyo metropolitan area. Plasma lipids and lipoproteins, cholesteryl ester transfer protein mass, apo E phenotype, body mass index, nutritional indices (serum albumin, prealbumin, transferrin), dietary intake, inflammation markers (C-reactive protein (CRP), interleukin-6 (IL-6)), activities of daily living, and cognitive function. In comparison with older people, the centenarians had low concentrations of total and low-density lipoprotein cholesterol (LDL-C) and a relative predominance of high-density lipoprotein 2 cholesterol. No environmental factor, except the number of apo E epsilon2 alleles, was a significant determinant of LDL-C and apo B, suggesting that the low apo B-containing lipoprotein in centenarians may be attributable to a genetic cause. Centenarians had elevated levels of lipoprotein (a) and decreased high-density lipoprotein cholesterol (HDL-C), which seem to be an unfavorable lipoprotein profile. Lower levels of HDL-C in the centenarians were associated with decreased serum albumin, elevated CRP and IL-6 levels, and cognitive impairment, suggesting that HDL-C could be a sensitive marker for frailty and comorbidity in the oldest old. Low levels of apo B-containing lipoproteins attributable to a genetic cause may be advantageous for longevity. Lipoprotein profiles in centenarians were consistently related to the subjects' nutritional status, inflammation markers, and apo E polymorphisms. The results provide evidence for the importance of maintaining nutritional status in the very old.

Selected Biochemical Parameters of Blood Serum in Soldiers Committing Self-Mutilation

This project attempts to establish a possible link between selected biochemical parameters (cholesterol and triglyceride concentrations and levels of malonyl dialdehyde and superoxide dismutase) in soldiers with autoaggressive behaviors. The study involved 33 soldiers treated for self-aggressive behavior from July 1, 1998, to June 30, 1999. Average patient age was 20.7 years. The control group consisted of 21 soldiers hospitalized for mental disturbances but not showing autoaggressive tendencies. Total cholesterol and activity of platelets, considering the generation of free radicals and triglyceride concentration levels, were determined in the blood serum of members of both groups. The results indicate significantly lower concentrations of total cholesterol in the serum of soldiers showing self-aggressive behaviors. Also, increased concentrations of malonyl dialdehyde in blood platelets and decreased superoxide dismutase activity were found in individuals prone to autoaggression. The results suggest that the dysfunction of oxidation-reduction processes in brain tissue leads to excessive generation of free radicals, which can cause brain cell damage and disturb metabolic processes, resulting in mental disturbances that may constitute a background for self-aggressive behavior. The decreased activity of superoxide dismutase is a major factor in the observed oxidation-reduction disturbances.

Low serum cholesterol and haemorrhagic stroke in men: Korea Medical Insurance Corporation Study

In some prospective studies, haemorrhagic stroke occurs more frequently in individuals with low serum cholesterol than in those with higher concentrations. We aimed to determine whether low total serum cholesterol is an independent risk factor for haemorrhagic stroke (intracerebral haemorrhage and subarachnoid haemorrhage) in South Korea, a country that has a population with relatively low concentrations of total serum cholesterol. We measured total serum cholesterol and other cardiovascular risk factors in 114,793 Korean men, aged between 35-59 years in 1990 and 1992, in a prospective observational study. We used data obtained in 1992 for smoking and alcohol consumption. We divided total serum cholesterol into quintiles (<4.31 mmol/L, 4.31-<4.74, 4.74-<5.16, 5.16-<5.69 and > or = 5.69). Our primary outcomes were hospital admissions and deaths from intracerebral and subarachnoid haemorrhage in a 6 year follow-up between 1993 and 1998. 528 men had a haemorrhagic stroke--372 intracerebral and 98 subarachnoid haemorrhage--and 58 were unspecified strokes. The relative risks of intracerebral haemorrhage in each quintile of total serum cholesterol (lowest to highest were: 1.22 (95% CI 0.88-1.69); 0.86 (0.60-1.21); 1.08 (0.78-1.48); and 1.03 (0.75-1.41). The corresponding relative risks for subarachnoid haemorrhage were: 1.44 (0.76-2.73); 1.13 (0.59-2.20); 1.21 (0.64-2.29); and 1.12 (0.59-2.14). Low total serum cholesterol is not an independent risk factor for either intracerebral or subarachnoid haemorrhagic stroke in Korean men.

Atherogenic lipid profile in elderly patients with ischaemic cerebrovascular disease

The significance of the link between plasma cholesterol concentrations and risk of cerebrovascular disease (CVD) in the elderly is still debated. In a case-control study we found that elderly patients with ischaemic CVD have an atherogenic lipid profile, despite having low or normal total cholesterol concentrations.

Apolipoprotein A1 Gene Polymorphisms and Risk of Early Coronary Disease

Genetic studies have identified polymorphisms at the apolipoprotein (Apo) A1 gene associated with HDL cholesterol and apolipoprotein levels, and a relationship between the severity of coronary artery disease and polymorphisms at the 5′-end of Apo A1 has been also reported. This study was designed to examine the relationship between polymorphism at the Apo A1 gene and the risk of early coronary artery disease. Furthermore, the association of the polymorphism with the classical risk factors was analyzed. A total of 176 male patients (mean age 43 ± 5 years) diagnosed as having unstable angina (53 cases) or myocardial infarction (123 cases) were prospectively evaluated. Data referring to hypertension, diabetes and tobacco consumption were recorded. The levels of total cholesterol, HDL cholesterol, Apo A1 and B and triglycerides were determined. DNA was obtained from the 176 patients and from 200 controls. In order to determine the Apo A1 genotypes at two polymorphic sites (G/A at –75 bp, and C/T at +83 bp), DNA was PCR amplified and digested with MspI. The frequency of carriers of the rare allele at the –75 bp site (M1–) was 0.34 in cases and 0.24 in controls (p < 0.05). The frequencies of the M1– allele among patients with angina and myocardial infarction were 0.43 (p = 0.009, angina vs. controls) and 0.30, respectively. No significant association between this polymorphism and other cardiovascular risk factors was found. No difference in the frequencies for carriers of the rare allele at the +83-bp polymorphism (M2) was observed among patients with angina (0.08 vs. 0.07) or myocardial infarction (0.04 vs. 0.07), and no association between this polymorphism and tobacco, hypertension and diabetes was noted. Patients carrying the rare M2– allele had a lower concentration of total cholesterol compared to those without this allele (183 ± 29 vs. 223 ± 54, p < 0.04) and HDL cholesterol was also lower among patients carrying the M2– (26 ± 4 vs. 33 ± 9, p < 0.02). In our community male patients with a diagnosis of coronary artery disease and age less than 50 years showed a higher frequency of the M1– allele at the –75-bp site of the Apo A1 gene. There was a significant increase in the frequency of the M1– allele in patients with unstable angina and no association with risk factors. In the +83-bp polymorphism there was no difference in the allelelic frequencies or the risk factors, except for the HDL cholesterol and total cholesterol where the patients with the allele M2– had lower levels than those homozygous for the M2+.