| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The regiochemical distribution of positive charges along cholesterol polyamine carbamates plays significant roles in modulating DNA binding affinity and lipofection Geall, A. J., M. A. Eaton, et al. (1999), FEBS Lett 459(3): 337-42. Abstract: We have quantified the effects of the regiochemical distribution of positive charges along the polyamine moiety in lipopolyamines for DNA molecular recognition. High affinity binding leads to charge neutralisation, DNA condensation and ultimately to lipofection. Binding affinities for calf thymus DNA were determined using an ethidium bromide displacement assay and condensation was detected by changes in turbidity using light scattering. The in vitro transfection competence of cholesterol polyamine carbamates was measured in CHO cells. In the design of DNA condensing and transfecting agents for non-viral gene therapy, the interrelationship of ammonium ions, not just their number, must be considered. |
| The regulation of beta-secretase by cholesterol and statins in Alzheimer's disease Sidera, C., R. Parsons, et al. (2005), J Neurol Sci 229-230: 269-73. Abstract: Epidemiologists have found a decreased risk of developing Alzheimer's disease (AD) in people taking statins (cholesterol biosynthesis inhibitors). We have reported previously that, in cell culture, lovastatin decreases the output of beta-amyloid, a peptide that is toxic to neurones, and is reputably the prime cause of neurodegeneration seen in AD. This report probes the mechanism of statin protection further by finding out how the protease beta-secretase, that releases beta-amyloid from its precursor protein, behaves under changed cholesterol levels induced by statins. We found that, with high cellular cholesterol levels, there is a decrease in glycosylation of mature oligosaccharides in beta-secretase, whereas in the presence of lovastatin, glycosylation progresses further. Moreover, lovastatin does not inhibit beta-secretase in vitro. Thus, the cholesterol and statin effects are due to changes in cellular targeting induced by changed cholesterol gradients. Some of these changes are mimicked by the action of U18666A, a cholesterol-transport inhibitor that produces a defect in cells seen in patients with Neimann Pick's disorder. |
| The regulation of cholesteryl ester metabolism by 17 beta-estradiol in macrophages. Activation of neutral cholesterol esterase Tomita, T., F. Sawamura, et al. (1995), Ann N Y Acad Sci 748: 637-9. Abstract: The mechanism for antiatherogenic effects of 17 beta-estradiol (E2) was investigated in J774 A.1 cells incubated with beta-VLDL. E2 at physiological concentrations (0.25 and 2.5 nM) inhibited an accumulation of cellular cholesteryl esters and enhanced their hydrolysis in foam cells. These phenomena were preceded by activation of neutral cholesterol esterase through an increase in cyclic AMP-dependent protein kinase activity. 17 alpha-estradiol, progesterone, and testosterone lacked such stimulatory effects on neutral cholesteryl esterase. |
| The regulation of hepatic lipase and cholesteryl ester transfer protein activity in the cholesterol fed rabbit Warren, R. J., D. L. Ebert, et al. (1991), Biochim Biophys Acta 1086(3): 354-8. Abstract: Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) activities are both increased in the rabbit by cholesterol feeding. The in vivo regulation of HL and CETP were explored by examining changes in specific steady-state mRNA levels upon cholesterol feeding. On feeding rabbits cholesterol, HL activity increased 3-fold after 2 days and remained at 2.6-times the control value at 28 days. Specific rabbit HL mRNA levels were assessed by dot blot analysis of liver poly (A)+ RNA hybridized with the human HL cDNA. No significant changes in liver HL mRNA accompanied the increase in activity seen at days 2 and 7. At day 28 a modest rise of 46% was observed. A significant rise in CETP activity, evident 7 days after the commencement of cholesterol feeding, was maintained until day 28 when it was 2.4-times the control value. Using the human CETP cDNA as probe, rabbit liver CETP mRNA was also found to increase by day 7, rising to 3.7-times control by day 28. The strong temporal relationship between the rise in CETP activity and mRNA (r = 0.55, P = 0.02) suggests that the regulation of CETP may be primarily effected by the levels of specific mRNA. In contrast, the discordance between levels of lipase activity and mRNA suggests that post-transcriptional events may be more important in the regulation of HL in the cholesterol fed rabbit. |
| The regulation of post-prandial cellular cholesterol metabolism in type 2 diabetic and non-diabetic subjects Stinson, J. C., D. Owens, et al. (1993), Diabet Med 10(5): 420-6. Abstract: The purpose of the study was to determine the effect of diabetes on the regulation of postprandial cholesterol metabolism. Four groups of patients (n = 8 for each group) were examined: Type 2 diabetic patients with and without hypercholesterolaemia and non-diabetic subjects with and without hypercholesterolaemia. Serum lipoproteins, lipoprotein composition, cellular cholesterol, and cellular cholesterol synthesis were measured before and 4 h after a high calorie meal. The BMI for the hypercholesterolaemic diabetic patients of 31.5 +/- 0.95 (SEM) was significantly higher than that for the control group of 26.2 +/- 1.0 (p < 0.01). Fasting triglyceride levels were significantly higher in the normocholesterolaemic and hypercholesterolaemic diabetic patients and in the hypercholesterolaemic non-diabetic subjects (1.45 +/- 0.22, 2.27 +/- 0.34, and 1.58 +/- 0.18 mmol l-1, respectively) compared with normocholesterolaemic non-diabetic subjects (0.75 +/- 0.12 mmol l-1: p < 0.01). The normocholesterolaemic and hypercholesterolaemic diabetic subjects had significantly lower fasting serum high density lipoprotein (HDL) (1.06 +/- 0.08 and 1.04 +/- 0.06 mmol l-1) compared to the corresponding non-diabetic groups (1.29 +/- 0.11 and 1.45 +/- 0.17 mmol l-1, p < 0.05). The esterified/free cholesterol ratio of very low density lipoprotein (including chylomicrons VLDL-C) decreased postprandially in all groups with an overall decrease of 1.33 to 0.83 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) |
| The relation between aerobic fitness and serum cholesterol levels in a large employed population Tucker, L. A. and M. Bagwell (1991), Am J Health Promot 6(1): 17-23. Abstract: BACKGROUND. The purpose of this epidemiologic study was to determine the extent to which aerobic fitness was associated with total cholesterol/HDL-C ratios greater than 5.0 in 10,455 adults. The confounding effects of age, gender, income, body fat, smoking, and alcohol use were also examined. METHODS. A step test was used to estimate aerobic fitness, and serum cholesterol was measured in a certified lab. Lifestyle information was gathered using written questionnaires, and body fat was assessed using skinfold measurements. RESULTS. High fitness levels were associated with low prevalence of elevated total/HDL-C ratios. After controlling for the potential confounders, adults classified as having excellent, very good, good, or fair aerobic fitness levels were.46.64.61, and.85 times as likely to have elevated ratios compared to poorly fit adults, respectively. High-level fitness was also related to high HDL-C levels and low total cholesterol levels. DISCUSSION. Cause-and-effect conclusions are not warranted; however, poorly fit adults appear to be at increased risk of elevated levels of serum cholesterol. |
| The relation between body mass index and plasma total cholesterol in a multiracial sample of US schoolchildren Resnicow, K. and A. Morabia (1990), Am J Epidemiol 132(6): 1083-90. Abstract: The relation between body mass index expressed as weight in kilograms divided by height in meters cubed (weight (kg)/height (m3)) and plasma total cholesterol was assessed in a sample of 11,389 US schoolchildren, aged 5-18 years, between 1984 and 1989. Among whites and Hispanics, a statistically significant nonlinear relation was found between weight (kg)/height (m3) and plasma total cholesterol. Mean cholesterol values increased exponentially above the 50th percentile of body mass index. Additionally, mean cholesterol levels as well as the odds of hypercholesterolemia (total cholesterol value greater than 180 mg/dl) were highest among children with weight (kg)/height (m3) values above the 95th percentile. Among black children, weight (kg)/height (m3) did not appear to be related to plasma total cholesterol. Possible explanations as well as public health implications of these findings are discussed. |
| The relation between cholesterol and haemorrhagic or ischaemic stroke in the Renfrew/Paisley study Hart, C. L., D. J. Hole, et al. (2000), J Epidemiol Community Health 54(11): 874-5. |
| The relation between two polymorphisms in the glucocorticoid receptor gene and body mass index, blood pressure and cholesterol in obese patients Di Blasio, A. M., E. F. van Rossum, et al. (2003), Clin Endocrinol (Oxf) 59(1): 68-74. Abstract: OBJECTIVE: We have recently reported that, in healthy elderly Dutch individuals, a N363S polymorphism in the glucocorticoid receptor (GR) gene is associated with higher sensitivity to low-dose dexamethasone (0.25 mg), evaluated as both cortisol suppression and insulin response, and with an increased body mass index (BMI). In the present study we investigated the role of the N363S polymorphism, and a BclI restriction site polymorphism in a group of Italian patients with severe obesity. DESIGN: Two hundred and seventy-nine patients (mean BMI 45.9 +/- 0.9 kg/m2) were genotyped using both PCR-restriction fragment length polymorphism analysis and Taqman Sequence Detection System. Determination of several metabolic and antropometric parameters was also performed in order to correlate them to the genotype. RESULTS: In this group of obese patients, 13 subjects (eight female, five males) were heterozygous for the N363S variant (allelic frequency 2.3%) and had significantly higher BMI (P < 0.04), resting energy expenditure (P < 0.03) and food intake (P < 0.01) when compared to wild-type homozygotes. When the data were analysed according to sex, female heterozygotes for the N363S allele had significantly higher BMI (P = 0.04), resting energy expenditure (P = 0.03) and food intake (P = 0.008) than obese women with the wild-type 363 GR gene. Male carriers of this variant also had higher values for these variables although the differences did not reach statistical significance. A case-control study with homozygous wild-type obese subjects which were age-, sex- and BMI-matched, revealed no difference in resting energy expenditure and food intake. The allele frequency of the BclI variant was 27% (89 females and 41 males out of 269 subjects). No differences in anthropometric and metabolic parameters were found between subjects heterozygous or homozygous for this variant GR in this obese population. However, when we studied the effect of the presence of the BclI polymorphism and the N363S variant in the same individual, we found that the subjects who carried both polymorphisms had a tendency towards higher systolic and diastolic blood pressure and significantly higher total and LDL-cholesterol levels (P = 0.005 and P = 0.05, respectively). DISCUSSION: Taking the results of this study and those obtained in the Dutch population, we speculate that heterozygous carriers of the N363S variant who develop obesity, may become even more obese, possibly because they have a hypersensitive insulin response and thus, via activation of lipogenesis, store fat more efficiently. Furthermore, these data suggest that N363S carriers who carry the BclI polymorphism as well, tend to have a slightly unfavourable cardiovascular profile. |
| The relation of documented coronary artery disease to levels of total cholesterol and high-density lipoprotein cholesterol Freedman, D. S., J. B. Croft, et al. (1994), Epidemiology 5(1): 80-7. Abstract: Recommendations for identifying persons at high risk for coronary heart disease are based primarily on levels of total and low-density lipoprotein cholesterol. We examined whether, given knowledge of these levels, information on the high-density lipoprotein cholesterol level would improve the prediction of arteriographically documented coronary artery disease among 591 men. We found that even at levels of total and low-density lipoprotein cholesterol considered desirable, high-density lipoprotein cholesterol was inversely related to disease severity. For example, among the 112 men with a total cholesterol level <180 mg per dl, the mean occlusion score (representing the overall severity of disease) was 107 among men with a high-density lipoprotein cholesterol level < or = 30 mg per dl vs a mean score of 52 among men with levels > or = 45 mg per dl. Furthermore, men with low levels of both low-density lipoprotein cholesterol (< 110 mg per dl) and high-density lipoprotein cholesterol (< or = 30 mg per dl) had as much occlusive disease as did men with high levels of both lipoprotein fractions. Given information on the ratio of high-density lipoprotein cholesterol to total cholesterol, the actual levels of the lipoprotein fractions did not improve disease prediction. Our results emphasize the importance of considering high-density lipoprotein cholesterol when assessing coronary heart disease risk. |
| The relation of high density lipoprotein cholesterol and its subfractions to apolipoprotein A-I and fasting triglycerides: the role of environmental factors. The Atherosclerosis Risk in Communities (ARIC) Study Patsch, W., A. R. Sharrett, et al. (1992), Am J Epidemiol 136(5): 546-57. Abstract: Cross-sectional analysis of four general representative populations of middle-aged adults in the United States in 1986-1989 provides estimates of the close relation of high density lipoprotein cholesterol (HDL cholesterol) to its major structural apolipoprotein (apolipoprotein A-I) and to fasting plasma triglyceride levels. HDL cholesterol differences of approximately 0.4 mg were associated with 1-mg differences in apolipoprotein A-I; differences of 20% in HDL cholesterol (reductions) were associated with triglyceride doublings. Variation in apolipoprotein A-I and triglyceride concentration together accounted for 66% of the population variance in HDL cholesterol. The uniformity of this pattern in the four race-sex groups studied suggests an important role of triglyceride-cholesterol transfer as a determinant of HDL cholesterol. The fundamental relations observed among HDL cholesterol, apolipoprotein A-I, and triglycerides were unaltered by levels of factors under personal volition. The volitional factors appeared to influence HDL cholesterol indirectly: Obesity and physical activity were affected primarily through their associations with triglycerides, and alcohol use and smoking through associations with apolipoprotein A-I. The association of alcohol use with elevated HDL cholesterol was attenuated in persons with greater body mass. |
| The relation of plasma triglyceride, apolipoprotein B, and high-density lipoprotein cholesterol to postheparin lipoprotein lipase activity is dependent on apolipoprotien E polymorphism St-Amand, J., S. Moorjanit, et al. (1996), Metabolism 45(2): 261-7. Abstract: Postheparin plasma (PH)-lipoprotein lipase (LPL) activity has been reported to be a significant correlate of plasma triglyceride and high-density lipoprotein cholesterol (HDL-C) levels. However, some studies have failed to observe these associations. In this regard, apolipoprotein (apo) E polymorphism may play an important role, since the apo E2 isoform has unfavorable effects on the catabolism of triglyceride-rich lipoprotein particles. We have thus examined the relationships between PH-LPL activity and plasma lipoprotein-lipid levels within groups of men classified on the basis of apo E phenotypes, to verify whether apo E polymorphism could alter these associations. In men carrying the apo E2 isoform (n = 12), PH-LPL activity showed a strong negative correlation with plasma triglyceride (r = -.72, P <.01), very-low-density lipoprotein (VLDL) triglyceride (VLDL-TG r = -.83, P <.001), and VLDL cholesterol (VLDL-C r = -.57, P <.05) levels and a positive correlation with plasma HDL-C (r =.87, P <.001) and HDL2-C (r=.90, P <.001) concentrations. These correlations were also noted for plasma apo B levels (r = -.65, P <.05), VLDL-apo B concentrations (r= -.76, P <.01), and the HDL-C to cholesterol ratio (r =.85, P <.001). In contrast, none of these associations were found in men carrying the apo E4 isoform (n = 11). In men homozygous for the apo E3 isoform (n = 29), PH-LPL activity was only significantly correlated with plasma HDL2-C levels (r =.46, P <.01). Results of the present study indicate that PH-LPL activity is related to plasma triglyceride, VLDL-TG, VLDL-C, VLDL-apo B, apo B, and HDL-C levels and the HDL-C to cholesterol ratio in men carrying the apo E2 isoform, but not in men homozygous for the apo E3 isoform or among apo E4 carriers. Thus, apo E polymorphism appears to modulate the effect of variation in PH-LPL activity on the plasma lipoprotein profile. |
| The relation of polymorphism of low-density lipoprotein receptor gene with serum cholesterol levels Fan, L. M. (1993), Zhonghua Yi Xue Za Zhi 73(4): 242-4, 256. Abstract: PvuII polymorphism of LDL receptor gene and serum lipid levels were analysed in 115 normolipidemic subjects and 57 individuals with hypercholesterolemia. A significant relationship was found between P2 allele and lower serum cholesterol level, suggesting that the LDL receptor may contribute to the variation in cholesterol levels in normolipidemic population. Although the frequency of P2 allele in the Chinese was lower than in westerners, the serum cholesterol levels in the Chinese were not higher or even lower than that in westerners. This might be attributed to the difference in diet, lifestyle or other genes which are related to cholesterol metabolism between the Chinese and westerners. |
| The relation of serum cholesterol to risk of coronary heart disease: implications for the elderly Pacala, J. T. (1990), J Am Board Fam Pract 3(4): 271-82. Abstract: Elevated cholesterol is a known risk factor for coronary heart disease (CHD) in young and middle-aged persons. Because of the high prevalence of CHD in a growing elderly population, physicians must decide whether to devote clinical attention to this condition in older patients. Longitudinal cohort studies show that while the association between serum cholesterol and CHD decreases after age 55 years, it still persists. Primary prevention trials performed mostly on middle-aged men have reduced the incidence rate of CHD through cholesterol lowering but they have yet to show a reduction in overall mortality. Secondary prevention studies of lipid alteration have reported decreased mortality and slowed progression of coronary stenoses, again in predominantly male subjects aged less than 60 years. Implications of these findings for care of older patients are discussed along with recommendations for clinical management and future research. |
| The relation of white blood cell count and atherogenic index ratio of LDL-cholesterol to HDL-cholesterol in Taiwan school children Liu, C. S., C. C. Lin, et al. (1999), Acta Paediatr Taiwan 40(5): 319-24. Abstract: White blood cell (WBC) count is an independent coronary risk factor in adults. To clarify the relation of WBC count and atherogenesity in children, we conducted a cross-sectional study in Taiwan from February to June 1996. A total of 3818 subjects were eligible in the final analyses. The ratio of low to high density lipoprotein cholesterol was calculated as atherogenic index. The 75th percentile of atherogenic index was calculated and used as cut-off point for high and low levels. The mean WBC count in children with high atherogenic index (6.82 x 10(9) cells/L) was significantly (p < 0.001) higher than those with low atherogenic index (6.58 x 10(9) cells/L). By multiple logistic regression analysis, higher WBC count (> or = 7.8 x 10(9) cells/L) was found to be an independent risk indicator of atherogenesity (odds ratio: 1.70, 95% confidence interval: 1.20-2.41) among obese children. Other significant factors associated with atherogenesity were gender, obesity, age, triglyceride and total cholesterol level. Our results indicate that obese children with higher WBC count have higher atherogenic index. |
| The relationship between 1H-NMR mobile lipid intensity and cholesterol in two human tumor multidrug resistant cell lines (MCF-7 and LoVo) Santini, M. T., R. Romano, et al. (2001), Biochim Biophys Acta 1531(1-2): 111-31. Abstract: The high resolution proton nuclear magnetic resonance (1H-NMR) spectra of two different cell lines exhibiting multidrug resistance (MDR) as demonstrated by the expression of the well-known energy-driven, membrane-bound 170 kDa P-glycoprotein pump known as Pgp were investigated. In particular, the mobile lipid (ML) profile, and the growth and biochemical characteristics of MCF-7 (human mammary carcinoma) and LoVo (human colon adenocarcinoma) sensitive and resistant tumor cells were compared. The results indicate that both MCF-7 and LoVo resistant cells have a higher ML intensity than their respective sensitive counterparts. However, since sensitive and resistant cells of each pair grow in the same manner, variations in growth characteristics do not appear to be the cause of the ML changes as has been suggested by other authors in non-resistant tumor cells. In order to investigate further the origin of the ML changes, lipid analyses were conducted in sensitive and resistant cell types. The results of these experiments show that resistant cells of both cell types have a greater amount of esterified cholesterol and saturated cholesteryl ester and triglyceride fatty acid than their sensitive counterparts. From a thorough analysis of the data obtained in this paper utilizing numerous techniques including biological, biophysical and biochemical ones, it is hypothesized that cholesterol and triglyceride play a pivotal role in inducing changes in NMR ML signals. The importance of these lipid variations in MDR is discussed in view of the controversy regarding the origin of ML signals and the paramount role played by the Pgp pump in resistance. |
| The relationship between breakfast habits and plasma cholesterol levels in schoolchildren Resnicow, K. (1991), J Sch Health 61(2): 81-5. Abstract: The relationship between breakfast habits and plasma total cholesterol (TC) levels was examined in a sample of 530 US schoolchildren ages 9-19. Based on response to a 124-item food checklist, subjects' usual breakfast habits were classified into one of six discrete categories: 1) Skipper, 2) Ready-to-Eat (RTE) cereal with Fiber, 3) Traditional Breakfast, 4) Chips or Sweets, 5) Other RTE, or 6) Mixed Breakfasts. Breakfast skippers, controlling for age, gender, and body mass index, had significantly (p less than 0.05) higher TC levels, 172 mg/dl, than breakfast consumers, 160 mg/dl. Among breakfast eaters, the mean TC of the "Fiber RTE" group was significantly lower (p less than 0.01) than all other breakfast consumers. Usual skippers were less likely to believe in the importance and benefits of breakfast as well as the need to eat foods high in fiber. These findings suggest that encouraging chronic breakfast skippers to modify their dietary habits may improve their nutritional status and possibly reduce their risk for future heart disease. |
| The relationship between cholesterol absorption and intestinal cholesterol synthesis in the diabetic rat model Gleeson, A., D. Owens, et al. (2000), Int J Exp Diabetes Res 1(3): 203-10. Abstract: The chylomicron remnant particle is thought to be particularly atherogenic and we have previously shown alterations in post-prandial lipoproteins which could contribute to their atherogenicity. Cholesterol metabolism is disturbed in diabetes, yet the effect of diabetes on intestinal cholesterol synthesis and absorption has rarely been investigated. The aim of this study was to examine cholesterol absorption and intestinal synthesis of cholesterol in the streptozotocin diabetic rat. Twelve diabetic rats were paired with 12 control rats. 14C-Cholesterol emulsion was administered and the lymph duct was canulated. Lymph was collected for 4h. At sacrifice blood was taken for plasma lipoprotein measurements. Chylomicrons were prepared from the lymph by ultracentrifugation and 14C-cholesterol content was determined by liquid scintillation counting. Lymph apolipoprotein B48 was isolated by gradient gel electrophoresis, and quantified by densitometric scanning. Serum triglyceride and cholesterol were greatly elevated in diabetic compared to control animals (260+/-90 and 9.8+/-8.0 mg/ml vs. 1.0+/-0.4 and 0.6+/-0.3 mg/ml, p < 0.0001 respectively). Lymph chylomicron apo B48 was similar in the two groups. Cholesterol absorption was not significantly different in diabetic compared to control rats but cholesterol synthesis was significantly higher in the diabetic animals (550+/-352 vs. 322+/-113 microg/h p < 0.03). There was a positive correlation between apo B48 and cholesterol absorption (r = 0.70, p < 0.01) in the diabetic rats and control rats (r = 0.71, p < 0.01) but no correlation between apo B48 and cholesterol synthesis in either group. This study demonstrates that cholesterol synthesis was increased in diabetes whereas cholesterol absorption was unaffected suggesting that intestinal cholesterol synthesis made an important contribution to the hypercholesterolaemia seen in the diabetic animals. |
| The relationship between cholesterol and stroke Jacobs, D. R. (1994), Health Rep 6(1): 87-93. Abstract: Epidemiologic studies generally show no relationship or a weak relationship between total stroke and total blood cholesterol level. Several Japanese epidemiologic studies of hemorrhagic stroke indicate an increased risk at lower levels of blood cholesterol. However, these studies, which do not include many people with high blood cholesterol levels, do not show an increase in stroke rate at high blood cholesterol levels. The Japanese findings for hemorrhagic stroke were replicated by the Honolulu Heart Study in migrants from Japan, and in the MRFIT Screening Study. These studies also show an increase in nonhemorrhagic stroke at the highest, but not at intermediate, levels of blood cholesterol. An extensive pathologic study of the relationship of blood cholesterol to hemorrhagic and nonhemorrhagic stroke was carried out by Dr. Konishi of Osaka. The pathology was strikingly different in the two conditions, one being atherosclerotic in the larger arteries (5 mm diameter), the other arteriolosclerotic in the intracerebral arterioles (200 microns in diameter). The relationship between blood cholesterol and arterial lesions is inverse for arteriolosclerosis and positive for atherosclerosis. It is concluded that blood cholesterol influences the development of stroke above and beyond the influence of blood pressure. Furthermore, its influence is opposite for hemorrhagic and nonhemorrhagic stroke. The relationship between blood cholesterol and atherosclerotic stroke does not appear to be as strong as it is between blood cholesterol and coronary heart disease. |
| The relationship between cholesterol and stroke: implications for antihyperlipidaemic therapy in older patients Sarti, C., M. Kaarisalo, et al. (2000), Drugs Aging 17(1): 33-51. Abstract: Various studies on the relationship between serum cholesterol level and the risk of stroke have been published recently. Subsequent reviews have extrapolated information on stroke from the clinical trials originally aimed at lowering cholesterol for the primary and secondary prevention of myocardial infarction (MI) in middle-aged patients. We have reviewed the epidemiological knowledge on the relationship between serum cholesterol levels and stroke, and also focused on possible reduction of the risk of stroke with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor treatment. Possible benefits from such therapy are particularly relevant for the elderly population which is at particularly high risk for stroke. The effects of serum cholesterol levels on the risk for haemorrhagic and ischaemic stroke have been evaluated. Indirect epidemiological evidence indicates that serum levels of total cholesterol and its subfractions are determinants of stroke, but their associations are relatively weak. When exploring the possible association of serum cholesterol levels with the increased risk of stroke with aging, we concluded that, as in younger adults, elevated total cholesterol and decreased high density lipoprotein-cholesterol levels predispose to ischaemic stroke in the elderly. The mechanism through which serum cholesterol levels increase stroke risk is based on its actions on the artery walls. Indirect evidence suggests that the reduction in the stroke risk with HMG-CoA reductase inhibitors is larger than would be expected with reduction of elevated serum cholesterol level alone. Therefore, antioxidant and endothelium-stabilising properties of HMG-CoA reductase inhibitors may contribute in reducing the risk of stroke in recipients. Lowering high serum cholesterol with HMG-CoA reductase inhibitors has been beneficial in the primary and secondary prevention of MI. No trials have specifically tested the effect of cholesterol lowering with HMG-CoA reductase inhibitors on stroke occurrence. High serum cholesterol levels are a risk factor for ischaemic stroke, although the risk imparted is lower than that for MI. Although the relative risk of stroke associated with elevated serum cholesterol levels is only moderate, its population attributable risk is high given the increase in the elderly population worldwide. The effect of cholesterol reduction with HMG-CoA reductase inhibitors on prevention of ischaemic stroke should be evaluated in prospective, randomised, placebo-controlled trials in the elderly. The tolerability of lipid-lowering drugs in the elderly and the cost effectiveness of primary prevention of stroke using lipid-lowering drugs also needs to be assessed in the elderly. |