Cholesterol Journal Articles

Record 241 to 260

A population-based approach to cholesterol control
Cohen, J. D. (1997), Am J Med 102(2A): 23-5.
Abstract: The large proportion of the population who have only modest or moderate hypercholesterolemia will experience more coronary events than the smaller percentage of people who are at higher risk from more extreme elevations of serum cholesterol. The high-risk individual strategy for prevention of coronary heart disease (CHD) can result in impressive declines in cholesterol, but the benefits will be concentrated at the upper end of the population distribution. On the other hand, a population strategy for coronary disease prevention will achieve a much more modest reduction of cholesterol, but these changes will be over the entire distribution and will reduce the risk of the much larger proportion of people with average cholesterol levels who otherwise would likely go untreated. In light of the fact that epidemiologic studies and long-term clinical trials predict that a 10% reduction in serum cholesterol will result in a 30% reduction in coronary events, the population strategy has the potential for an enormous impact in reducing CHD, which, despite our great success over the past two decades, still remains the number one killer in the United States.

A porcine homolog of the major secretory protein of human epididymis, HE1, specifically binds cholesterol
Okamura, N., S. Kiuchi, et al. (1999), Biochim Biophys Acta 1438(3): 377-87.
Abstract: A porcine homolog of the major secretory protein of human epididymis, HE1, was for the first time purified from the porcine cauda epididymal fluid. The HE1 homolog was secreted into the epididymal fluid as a 19-kDa glycoprotein, whose sugar moiety was gradually processed to form a 16-kDa protein during transit through the epididymis. The HE1 homolog mRNA was detected only in the caput and corpus epididymis among the porcine tissues examined. The purified HE1 homolog specifically bound cholesterol with high affinity (Kd=2. 3 microM). The binding stoichiometry was determined to be 0.94 mol/mol, suggesting that 1 mol of cholesterol binds to 1 mol of the protein. It was also found that the HE1 homolog is a major cholesterol-binding protein in the porcine epididymal fluid. The possibility that the HE1 homolog is involved in the regulation of the lipid composition of the sperm membranes during the maturation in epididymis is discussed.

A possible role of cholesterol-sphingomyelin/phosphatidylcholine in nuclear matrix during rat liver regeneration
Albi, E., S. Cataldi, et al. (2003), J Hepatol 38(5): 623-8.
Abstract: BACKGROUND/AIMS: Phospholipids and cholesterol in chromatin have been previously demonstrated. The lipid fraction changes during cell proliferation in relation to activation of enzymes of phospholipid metabolism. The aim of the present work is to clarify if chromatin lipids may derive or not from nuclear matrix and if they have different roles. METHODS: The subnuclear fractions were isolated from rat hepatocyte nuclei and the lipid fraction was extracted and analysed by chromatography in normal and regenerating liver. The phosphatidylcholine-sphingomyelin metabolism enzymes activity was assayed, by using radioactive substrates. RESULTS: In nuclear matrix, cholesterol and sphingomyelin are respectively five and three times higher than those present in chromatin; the amount of phosphatidylcholine, which it is enriched in saturated fatty acids, is lower, thus indicating a less fluid structure. The lower content in phosphatidylcholine may be justified by the phosphatidylcholine-dependent phospholipase C activity, which increases during liver regeneration, reaching a peak at the beginning of S-phase, when also cholesterol and sphingomyelin increase. CONCLUSIONS: The nuclear matrix lipids are independent from chromatin lipids; the ratio cholesterol-sphingomyelin/phosphatidylcholine is higher and, as a consequence, nuclear matrix is less fluid in relation to DNA synthesis, suggesting a specific role of nuclear matrix as a structure involved in DNA duplication.

A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCA1 mRNA and stimulating cholesterol efflux
Sparrow, C. P., J. Baffic, et al. (2002), J Biol Chem 277(12): 10021-7.
Abstract: The LXR nuclear receptors are intracellular sensors of cholesterol excess and are activated by various oxysterols. LXRs have been shown to regulate multiple genes of lipid metabolism, including ABCA1 (formerly known as ABC1). ABCA1 is a lipid pump that effluxes cholesterol and phospholipid out of cells. ABCA1 deficiency causes extremely low high density lipoprotein (HDL) levels, demonstrating the importance of ABCA1 in the formation of HDL. The present work shows that the acetyl-podocarpic dimer (APD) is a potent, selective agonist for both LXRalpha (NR1H3) and LXRbeta (NR1H2). In transient transactivation assays, APD was approximately 1000-fold more potent, and yielded approximately 6-fold greater maximal stimulation, than the widely used LXR agonist 22-(R)-hydroxycholesterol. APD induced ABCA1 mRNA levels, and increased efflux of both cholesterol and phospholipid, from multiple cell types. Gas chromatography-mass spectrometry measurements demonstrated that APD stimulated efflux of endogenous cholesterol, eliminating any possible artifacts of cholesterol labeling. For both mRNA induction and stimulation of cholesterol efflux, APD was found to be more effective than was cholesterol loading. Taken together, these data show that APD is a more effective LXR agonist than endogenous oxysterols. LXR agonists may therefore be useful for the prevention and treatment of atherosclerosis, especially in the context of low HDL levels.

A potential role for sterol carrier protein-2 in cholesterol transfer to mitochondria
Gallegos, A. M., J. K. Schoer, et al. (2000), Chem Phys Lipids 105(1): 9-29.
Abstract: Mitochondrial cholesterol oxidation rapidly depletes cholesterol from the relatively cholesterol-poor mitochondrial membranes. However, almost nothing is known regarding potential mechanism(s) whereby the mitochondrial cholesterol pool is restored. Since most exogenous cholesterol enters the cell via the lysosomal pathway, this could be a source of mitochondrial cholesterol. In the present study, an in vitro fluorescent sterol transfer assay was used to examine whether the lysosomal membrane could be a putative cholesterol donor to mitochondria. First, it was shown that spontaneous sterol transfer from lysosomal to mitochondrial membranes was very slow (initial rate, 0.316 +/- 0.032 pmol/min). This was due, in part, to the fact that 90% of the lysosomal membrane sterol was not exchangeable, while the remaining 10% also had a relatively long half-time of exchange t(1/2) = 202 +/- 19 min. Second, the intracellular sterol carrier protein-2 (SCP-2) and its precursor (pro-SCP-2) increased the initial rate of sterol transfer from the lysosomal to mitochondrial membrane by 5.2- and 2.0-fold, respectively, but not in the reverse direction. The enhanced sterol transfer was due to a 3.5-fold increase in exchangeable sterol pool size and to induction of a very rapidly (t(1/2) = 4.1 +/- 0.6 min) exchangeable sterol pool. Confocal fluorescence imaging and indirect immunocytochemistry colocalized significant amounts of SCP-2 with the mitochondrial marker enzyme cytochrome oxidase in transfected L-cells overexpressing SCP-2. In summary, SCP-2 and pro-SCP-2 both stimulated molecular sterol transfer from lysosomal to mitochondrial membranes, suggesting a potential mechanism for replenishing mitochondrial cholesterol pools depleted by cholesterol oxidation.

A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis
Chawla, A., W. A. Boisvert, et al. (2001), Mol Cell 7(1): 161-71.
Abstract: Previous work has implicated PPAR gamma in the regulation of CD36 expression and macrophage uptake of oxidized LDL (oxLDL). We provide evidence here that in addition to lipid uptake, PPAR gamma regulates a pathway of cholesterol efflux. PPAR gamma induces ABCA1 expression and cholesterol removal from macrophages through a transcriptional cascade mediated by the nuclear receptor LXR alpha. Ligand activation of PPAR gamma leads to primary induction of LXR alpha and to coupled induction of ABCA1. Transplantation of PPAR gamma null bone marrow into LDLR -/- mice results in a significant increase in atherosclerosis, consistent with the hypothesis that regulation of LXR alpha and ABCA1 expression is protective in vivo. Thus, we propose that PPAR gamma coordinates a complex physiologic response to oxLDL that involves particle uptake, processing, and cholesterol removal through ABCA1.

A preliminary study of misclassification of blood cholesterol levels in an adolescent population
Rimmer, J. H. and M. A. Looney (1994), Res Q Exerc Sport 65(4): 382-5.

A promoter polymorphism in cholesterol 7alpha-hydroxylase interacts with apolipoprotein E genotype in the LDL-lowering response to atorvastatin
Kajinami, K., M. E. Brousseau, et al. (2005), Atherosclerosis 180(2): 407-15.
Abstract: Bile-acid biosynthesis is a key determinant of intracellular cholesterol and, in turn, cholesterol synthesis rate in hepatocytes. This suggests that variation in the cholesterol 7alpha-hydroxylase gene (CYP7A1), a key enzyme in bile-acid biosynthesis, may influence the statin response. To test this hypothesis, a promoter polymorphism (A-204C) in CYP7A1 was examined in 324 hypercholesterolemic patients treated with atorvastatin 10mg. The variant C allele was significantly and independently associated with poor LDL cholesterol reductions; -39% in wild type allele homozygotes, -37% in variant allele heterozygotes, and -34% in variant allele homozygotes (p<0.0001 for trend). Differences were more striking in men, and were enhanced by the coexistence of common variants of apolipoprotein E gene (APOE), epsilon2 or epsilon4. In subjects having wild type alleles at both loci, the mean reduction in LDL cholesterol was -40%, while the value in subjects having two CYP7A1 variant alleles and at least one variant APOE allele was -31% (p<0.0001). Combination analysis of these two loci more accurately predicted the achievement of goal LDL cholesterol, than did both single locus analysis. We concluded that the CYP7A1 A-204C promoter variant was associated with poor response to atorvastatin, which were additively enhanced by common variants in another locus, APOE.

A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population
Shioji, K., J. Nishioka, et al. (2004), J Hum Genet 49(3): 141-7.
Abstract: To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 (ABCA1) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1. After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(-273)C (P=0.0074), C(-297)T (P=0.0195), and IMS-JST071749 (P=0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(-273)C genotype was influential in another set of subjects (P=0.0310, n=743). However, the distribution of the ABCA1 G(-273)C genotype in subjects with MI (n=598) was not different from that in the control population (n=801). These results indicate that ABCA1 G(-273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.

A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction
Stampfer, M. J., F. M. Sacks, et al. (1991), N Engl J Med 325(6): 373-81.
Abstract: BACKGROUND. The independent contributions of subfractions of high-density lipoprotein (HDL) cholesterol (HDL2 and HDL3) and apolipoproteins in predicting the risk of myocardial infarction are unclear. Prospective data are sparse, but HDL2 is widely believed to be a more important predictor than HDL3. METHODS. Blood samples were collected at base line from 14,916 men (ages, 40 to 84 years) who were participants in the Physicians' Health Study. After five years of follow-up, plasma samples from 246 men with new myocardial infarction (case subjects) were analyzed together with specimens from 246 men matched to them for age and smoking status who had not had a myocardial infarction. RESULTS. The levels of total cholesterol and apolipoprotein B-100 were significantly associated with an increased risk of myocardial infarction (data on levels of low-density lipoprotein cholesterol were unavailable). Both HDL cholesterol and HDL2 levels were associated with a substantially decreased risk of myocardial infarction, but the HDL3 level was the strongest predictor; the relative risk was 0.3 (95 percent confidence interval, 0.2 to 0.6) for those in the fifth of the group with the highest HDL3 levels, as compared with the fifth with the lowest levels. The benefit of a higher HDL cholesterol level was most pronounced among those with lower total cholesterol levels. Levels of apolipoprotein A-I and apolipoprotein A-II were also associated with decreased risk. However, the levels of HDL subfractions and apolipoproteins did not add significantly to the value of a multivariate model that included the ratio of total to HDL cholesterol in predicting myocardial infarction, whereas that ratio remained a significant independent predictor of risk. After adjustment for other risk factors, a change of one unit in the ratio of total to HDL cholesterol was associated with a 53 percent change in risk (95 percent confidence interval, 26 percent to 85 percent). CONCLUSIONS. This study underscores the importance of HDL cholesterol in predicting the risk of myocardial infarction and demonstrates protective effects of both the HDL3 and HDL2 subfractions of HDL cholesterol. We found little or no predictive value for the levels of apolipoproteins A-I, A-II, and B or HDL subfractions after conventional risk factors and the ratio of total to HDL cholesterol were considered.

A prospective study on the prevalence of metabolic syndrome among healthy french families: two cardiovascular risk factors (HDL cholesterol and tumor necrosis factor-alpha) are revealed in the offspring of parents with metabolic syndrome
Maumus, S., B. Marie, et al. (2005), Diabetes Care 28(3): 675-82.
Abstract: OBJECTIVE: The purpose of this study was to estimate the longitudinal variation of prevalence of metabolic syndrome within French families and to observe biological parameters involved in cardiovascular disease among their offspring. RESEARCH DESIGN AND METHODS: Three hundred seventy-one apparently healthy families (1,366 individuals) taken from the STANISLAS cohort were studied. The subjects were examined at two time points with a 5-year interval (t(0) and t(+5)). The crude prevalence of metabolic syndrome was assessed among parents according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP) definition. RESULTS: The prevalence of metabolic syndrome was 5.9% in men and 2.1% in women at t(0), rising to 7.2 and 5.4% in men and women, respectively, at t(+5). Children of parents having metabolic syndrome showed higher levels of tumor necrosis factor-alpha (TNF-alpha), whereas their HDL cholesterol and apolipoprotein (apo) E concentrations were lower compared with those of age- and sex-matched control subjects (P

A prospective, randomized trial of phenytoin in nonepileptic subjects with reduced HDL cholesterol
Miller, M., R. G. Burgan, et al. (1995), Arterioscler Thromb Vasc Biol 15(12): 2151-6.
Abstract: Observational studies have demonstrated a positive association between phenytoin use and HDL cholesterol (HDL-C). Our goal was to determine whether phenytoin raises HDL-C in nonepileptic subjects at risk for coronary artery disease. We performed a double-blind, placebo-controlled, parallel-group study in 41 subjects with reduced levels of HDL-C. Subjects were placed on an American Heart Association Step I diet and were randomized to receive either phenytoin or placebo for 3 months. Serum levels of phenytoin were monitored and adjusted to between 7.5 and 15 micrograms/mL. Fasting levels of lipids and lipoproteins were determined twice at baseline (weeks -2 and -1) and during the treatment phase of the study (weeks 11 and 12). Compared with dietary baseline, phenytoin-treated subjects experienced significant paired percent increases in total HDL-C (12.4%; P <.01), an effect confined to the HDL2 subfraction (137%; P <.01). The paired percent increases in HDL-C and HDL2 levels remained significant after adjustment for placebo (P <.05, P <.025, respectively). There were no significant differences in the paired percent changes from dietary baseline in total cholesterol, triglyceride, or LDL cholesterol levels between placebo and phenytoin-treated groups. The significant paired percent increases in total HDL-C and HDL2 from dietary baseline suggest a potential role for phenytoin in subjects with reduced levels of HDL-C.

A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood
Brown, M. S. and J. L. Goldstein (1999), Proc Natl Acad Sci U S A 96(20): 11041-8.
Abstract: The integrity of cell membranes is maintained by a balance between the amount of cholesterol and the amounts of unsaturated and saturated fatty acids in phospholipids. This balance is maintained by membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs) that activate genes encoding enzymes of cholesterol and fatty acid biosynthesis. To enhance transcription, the active NH(2)-terminal domains of SREBPs are released from endoplasmic reticulum membranes by two sequential cleavages. The first is catalyzed by Site-1 protease (S1P), a membrane-bound subtilisin-related serine protease that cleaves the hydrophilic loop of SREBP that projects into the endoplasmic reticulum lumen. The second cleavage, at Site-2, requires the action of S2P, a hydrophobic protein that appears to be a zinc metalloprotease. This cleavage is unusual because it occurs within a membrane-spanning domain of SREBP. Sterols block SREBP processing by inhibiting S1P. This response is mediated by SREBP cleavage-activating protein (SCAP), a regulatory protein that activates S1P and also serves as a sterol sensor, losing its activity when sterols overaccumulate in cells. These regulated proteolytic cleavage reactions are ultimately responsible for controlling the level of cholesterol in membranes, cells, and blood.

A public health approach to cholesterol. Confronting the 'TV-auto-supermarket society'
Bodenheimer, T. (1991), West J Med 154(3): 344-8.
Abstract: Coronary heart disease has been proved to be associated with a "high-risk" diet and with elevated blood cholesterol levels. The National Cholesterol Education Program has embarked on a campaign based on intensive medical treatment of 60 million Americans with high blood cholesterol levels, but the degree of benefit of dietary change or pharmaceutical intervention or both to reduce blood cholesterol values remains a subject of disagreement within the scientific community. Evidence from comparative international studies suggests that to lower coronary heart disease mortality substantially, dietary alterations and general societal changes must be greater than those possible under the National Cholesterol Education Program's approach of physician-centered patient counseling. The nation's priority to prevent coronary heart disease should be a public policy approach, the goal of which is to reduce for the entire population all coronary disease risk factors. In the dietary area, three proposals to reduce the availability of atherogenic foods are the use of warning labels on atherogenic foods, the prohibition of advertising for such high-risk foods, and the imposition of an excise tax on the same foods. We must confront the "TV-auto-supermarket society" that underlies our nation's high rate of coronary heart disease.

A public health model for cardiovascular risk reduction. Impact of cholesterol screening with brief nonphysician counseling
Gemson, D. H., R. P. Sloan, et al. (1990), Arch Intern Med 150(5): 985-9.
Abstract: To examine the impact of cholesterol screening with brief nonphysician counseling on cardiovascular risk factors, 886 employees at a large financial services firm underwent fingerstick screening followed by brief (3- to 5-minute) counseling by a registered nurse. At the 6-month follow-up, there were significant declines in total cholesterol levels (5.9 to 5.5 mmol/L 228 to 213 mg/dL), weight (78 to 75 kg), blood pressure (119/78 to 115/75 mm Hg), and number of people reporting smoking (16.8% to 14.5%) among participants with a baseline cholesterol value of 5.2 mmol/L (200 mg/dL) or greater. A randomized experiment was conducted on 137 participants initially classified as having a "borderline-high blood cholesterol" level (5.2 to 6.2 mmol/L 200 to 239 mg/dL) to test the impact of frequency of follow-up. Those receiving frequent follow-up (cholesterol measurement and brief counseling at 2, 4, and 6 months) reported significantly greater dietary change and demonstrated a trend toward greater declines in total cholesterol compared with those receiving follow-up at 6 months only. The results of this study support the feasibility and efficacy of cholesterol screening utilizing brief nonphysician counseling on multiple cardiovascular risk factors and suggest an enhanced effect when patients receive more frequent follow-up.

A quantitative assessment of the influence of permanent kinks on the mixing behavior of phospholipids in cholesterol-rich bilayers
Jing, B., N. Tokutake, et al. (2004), J Am Chem Soc 126(47): 15344-5.

A quantitative model for the dependence of solute permeability on peptide and cholesterol content in biomembranes
Xiang, T. X., J. Chen, et al. (2000), J Membr Biol 177(2): 137-48.
Abstract: The influence of varying concentrations of a transmembrane peptide, gramicidin A (gA), and cholesterol (Chol) on the passive permeation of p-methylhippuric acid (MHA) and alpha-carbamoyl-p-methylhippuric acid (CMHA) across egg-lecithin membranes (EPC) has been investigated in vesicle efflux experiments. Incorporation of 0.25 volume fraction of gA in its nonchannel conformation increased the permeability coefficient (Pm) for CMHA by a factor of 6.0 +/- 1.8 but did not alter Pm for MHA, a more lipophilic permeant. In contrast, incorporation of 0.26 volume fraction Chol with no added protein decreased the Pm values for both CMHA and MHA by similar factors of 4.2 +/- 1.1 and 3.5 +/- 1.2, respectively. A quantitative structure-transport model has been developed to account for the dependence of Pm on the membrane concentrations of gA and Chol in terms of induced changes in both membrane chain ordering and hydrophobicity. Chain ordering is assumed to affect Pm for both permeants similarly since they are comparable in molecular size, while changes in Pm ratios in the presence of gA or Chol are attributed to alterations in membrane hydrophobicity. Changes in lipid chain ordering were detected by monitoring membrane fluidity using fluorescence anisotropy of 1-4-(trimethylamino)phenyl-6-phenylhexa-1,3,5-triene incorporated into the membranes. The influence of additives on membrane hydrophobicity, which governs Pm ratios through effects on solute partitioning into the barrier domain, were rationalized within the framework of regular solution theory using solubility parameters as a measure of membrane hydrophobicity. Fits of the Pm ratios using the theoretical model yielded solubility parameters for gA and Chol in EPC membranes of 13.2 and 7.7 (cal/ml)(1/2), respectively, suggesting that gA decreases the barrier domain hydrophobicity while Chol has a minimal effect on barrier hydrophobicity. After correcting for barrier domain hydrophobicity, permeability decrements due to membrane ordering induced by gA or Chol were found to exhibit a strong correlation with membrane order as predicted by free-surface-area theory, regardless of whether gA or Chol is used as the ordering agent.

A randomized controlled trial of a physician-directed treatment program for low-income patients with high blood cholesterol: the Southeast Cholesterol Project
Keyserling, T. C., A. S. Ammerman, et al. (1997), Arch Fam Med 6(2): 135-45.
Abstract: OBJECTIVE: To assess the effectiveness of a cholesterol-lowering intervention designed to facilitate the management of hypercholesterolemia by primary care clinicians. DESIGN: Randomized controlled trial, with randomization of clinician-patient groups. SETTING: Twenty-one community and rural health centers in North Carolina and Virginia. PARTICIPANTS: Primary care clinicians (n = 42, 71% physicians) and the patients they enrolled with high cholesterol (n = 372). Twenty-two clinicians were randomized to give the special intervention (184 patients) and 20 to give usual care (188 patients). Two thirds of participating patients were women, 40% were African American, and 11% were Native American. INTERVENTION: A 90-minute tutorial to train clinicians how to use a structured assessment and treatment program (Food for Heart Program) consisting of a brief dietary assessment and three 5- to 10-minute dietary counseling sessions given by the primary care clinician, referral to a local dietitian if the low-density lipoprotein cholesterol (LDL-C) remained elevated at 4-month follow-up, and a prompt for the clinician to consider lipid-lowering medication based on the LDL-C at 7-month follow-up. MAIN OUTCOME MEASURES: Changes in total and LDL cholesterol at 4-month follow-up and averaged over a 1-year follow-up period (4-, 7-, and 12-month follow-up). RESULTS: At 4-month follow-up, total cholesterol decreased 0.33 mmol/L (12.6 mg/dL) in the intervention group and 0.21 mmol/L (8.3 mg/dL) in the control group: the difference was 0.11 mmol/L (4.2 mg/dL) (90% confidence interval CI, -0.02 to 0.24 mmol/L -0.7 to 9.1 mg/dL). The average reduction during the 1-year follow-up period was 0.09 mmol/L (3.6 mg/dL) greater in the intervention group (90% CI, -0.01 to 0.19 mmol/L -0.3 to 7.5 mg/dL). Eight percent of intervention patients were taking lipid-lowering medication at follow-up visits compared with 15% of control patients. In a subgroup analysis restricted to the 89% of returnees who were not taking lipid-lowering medication, the reduction in total cholesterol at 4-month follow-up was 0.14 mmol/L (5.5 mg/dL) greater in the intervention group (95% CI, 0.01 to 0.28 mmol/L 0.3 to 10.7 mg/dL); averaged over 1 year, it was 0.14 mmol/L (5.3 mg/dL) greater (95% CI, 0.03 to 0.24 mmol/L 1.2 to 9.4 mg/dL). Changes in LDL-C were similar. CONCLUSIONS: Total cholesterol and LDL-C decreased more in the intervention group than in the control group. Overall, the difference in lipid reduction between groups was modest and of borderline statistical significance; among participants who did not take lipid-lowering medication during follow-up, the difference in lipid reduction between groups was larger. We conclude that primary care clinicians can be trained to give a cholesterol-lowering intervention to low-income patients that results in modest, short-term reductions in total cholesterol and LDL-C.

A randomized controlled trial of a public health nurse directed treatment program for rural patients with high blood cholesterol
Ammerman, A. S., T. C. Keyserling, et al. (2003), Prev Med 36(3): 340-51.
Abstract: BACKGROUND: Many rural residents do not have access to high-quality nutrition counseling for high blood cholesterol. The objective of this study was to assess the effectiveness of an intervention program designed to facilitate dietary counseling for hypercholesterolemia by rural public health nurses. METHODS: Eight health departments (216 participants) were randomized to give the special intervention (SI) and nine (252 participants) to give the minimal intervention (MI). The SI consisted of three individual diet counseling sessions given by a public health nurse, using a structured dietary intervention (Food for Heart Program), referral to a nutritionist if lipid goals were not achieved at 3-month follow-up, and a reinforcement phone call and newsletters. Diet was assessed by the Dietary Risk Assessment (DRA), a validated food frequency questionnaire, at baseline, 3-, and 12-month follow-up; blood lipids and weight were assessed at baseline, 3-, 6-, and 12-month follow-up. RESULTS: Participants were largely female (71%), older (mean age 55), and white (80%). At 3-month follow-up, the average reduction (indicating dietary improvement) in total Dietary Risk Assessment score was 3.7 units greater in the SI group (95% confidence interval CI 1.9 to 5.5, P = 0.0006), while both groups experienced a similar reduction in blood cholesterol, 14.1 mg/dL (0.37 mmol/L) for SI and 14.5 mg/dL (0.38 mmol/L) for minimal intervention group (difference -0.4 mg/dL -0.010 mmol/L, 95% CI -12.5 to 11.7 -0.32 to 0.30, P = 0.9). At 12-month follow-up, the reduction in total Dietary Risk Assessment score was 2.1 units greater in the SI group (95% CI 0.8 to 3.5, P = 0.005), while the reduction in blood cholesterol was similar in both groups, 18.4 mg/dL (0.48 mmol/L) for SI and 15.6 mg/dL (0.40 mmol/L) for minimal intervention group (difference 2.8 mg/dL 0.07 mmol/L, 95% CI -7.5 to 13.1 -0.19 to 0.34, P = 0.6). During follow-up, weight loss was greater in the SI group; the difference between groups was statistically significant at 3 (1.9 lb 0.86 kg, 95% CI 0.3 to 3.4 0.14 to 1.55, P = 0.022) and 6 months (2.1 lb 0.95 kg, 95% CI 0.1 to 4.1 0.04 to 1.86, P = 0.04). At 12 months, the difference was not significant (1.6 lb 0.73 kg, 95% CI -0.05 to 3.7 -0.02 to 1.68, P = 0.13). CONCLUSIONS: Improvement in self-reported dietary intake was significantly greater in the SI group, while reduction in blood cholesterol was similar in both groups.

A randomized crossover study to evaluate LDL-cholesterol lowering effect of a generic product of simvastatin (Unison Company) compared to simvastatin (Zocor) in hypercholesterolemic subjects
Assawawitoontip, S. and V. Wiwanitkit (2002), J Med Assoc Thai 85 Suppl 1: S118-24.
Abstract: It is agreed that people with a high blood LDL-cholesterol level will have a higher risk of coronary heart disease (CAD) than those with low blood LDL-cholesterol level. Because of the present National Drug Strategy of Thailand, the promotion of "in-country production" of a generic drug has been established. Simvastatin is one of the drugs in this strategy. In this, the primary report of a randomized crossover study with washout period for a cholesterol lowering effect in a generic product of simvastatin (Unison company) which was compared to the original simvastatin (Zocor) hypercholesterolemic to the subjects were presented. Simvastatin used in this study were derived from two sources. The first group was the original product (Zocor), dosage 10 mg, Lot No IC4/36(N) from Merck Sharp & Dohme Company and the second group was a generic product, dosage 10 mg, Lot No T05/080 and T06/109 from Unison Company. All simvastatin tablets from the first and second sources were inserted into closed capsule of the same shape and called drug A and drug B, respectively. Both the physician in-charge and the subjects in this study were blinded for the content inside the capsule (Double blind). Thirty drug capsules were put into a sachet and distributed to the subject at each visit. The interval between each visit was 4 weeks. All subjects were asked to bring back the residual capsule within the sachet to the researcher at each visit in order to evaluate the subject's compliance. All subjects had physical examination and blood tests at each visit. Furthermore, all subjects were advised to practice diet control and regular in-take of the drug capsule daily after their evening meal. All 48 subjects were randomly allocated into 2 groups. This study was run as a randomized crossover study. After taking the drugs for the first 8 weeks, no statistically significant difference of blood LDL-cholesterol between the first and second group was detected. After a 4 week washout period, crossover and taking the drugs for the last 8 weeks, no statistically significant difference of blood LDL-cholesterol between the first and second group was detected. At the end of this study, comparing both groups by ANOVA crossover test, no statistically significant difference of blood LDL-cholesterol between the first and second group was detected.

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