| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Long-term effects of a cholesterol-free diet on serum cholesterol levels in Zen monks Otani, H., T. Kita, et al. (1992), N Engl J Med 326(6): 416. |
| Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) Teo, K. K., J. R. Burton, et al. (2000), Circulation 102(15): 1748-54. Abstract: BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere. |
| Long-term effects of dietary fiber supplementation on serum glucose and lipoprotein levels in diabetic rats fed a high cholesterol diet Hozumi, T., M. Yoshida, et al. (1995), Endocr J 42(2): 187-92. Abstract: We have shown that cholesterol-fed diabetic rats developed atheromatous lesions in the aorta and coronary arteries, which were not observed in cholesterol-fed diabetic rats receiving concomitant supplementation with 15% glucomannan, a soluble dietary fiber concentrate. The present study was designed to examine the effects of the dietary fiber supplementation on serum levels of glucose and lipoproteins in cholesterol-fed diabetic rats. Feeding a diet containing 1.5% cholesterol (wt/wt) and 0.37% cholic acid for 18 weeks to rats made diabetic by streptozotocin (35 mg/kg body weight, iv) produced moderate hyperglycemia and moderate hypercholesterolemia, the latter being characterized by high concentrations not only of low density lipoproteins but also intermediate density lipoproteins and very low density lipoproteins. These changes in serum lipoproteins and hyperglycemia were substantially reduced by 18 weeks of supplementation with glucomannan but high density lipoprotein cholesterol and triglyceride levels did not change after feeding a cholesterol-rich diet in the presence or absence of glucomannan supplementation. These results suggest that amelioration in hyperlipoproteinemia and hyperglycemia induced by the dietary fiber supplementation may help retard or prevent the atheromatous formation found in cholesterol-fed diabetic rats. |
| Long-term effects of serum cholesterol on bone mineral density in women and men: the Framingham Osteoporosis Study Samelson, E. J., L. A. Cupples, et al. (2004), Bone 34(3): 557-61. Abstract: Laboratory studies have suggested a role for cholesterol in the pathogenesis of both osteoporosis and atherosclerosis. The purpose of this prospective study was to assess whether cholesterol levels, repeatedly measured over three decades in young and middle-aged adult women and men, predicted bone mineral density (BMD) at advanced age. Study participants included 712 women and 450 men enrolled in the Framingham Osteoporosis Study, aged 32-61 years at baseline (1953-55) who underwent bone densitometry 34 years later (1988-1989). BMD was measured at the proximal femur (neck, trochanter, and Ward's triangle) and lumbar spine using dual-photon absorptiometry and at the one-third radial shaft and ultradistal radius using single-photon absorptiometry. Sex-specific multivariable linear regression was used to model each BMD site as a function of total cholesterol level, adjusted for age, cigarette smoking, alcohol consumption, body mass index, systolic blood pressure, diabetes, and estrogen use (women). No significant association between total cholesterol and BMD was found in women for any of the bone sites considered. For example, adjusted mean BMD at the lumbar spine was similar in women from the lowest to highest quartile of total cholesterol, respectively, 1.07, 1.08, 1.06, 1.07 g/cm2; P for trend=0.98. Similarly, the findings in men largely showed no association between cholesterol and BMD, although there was an isolated finding of a statistically significant trend in decreasing mean radial shaft BMD with increasing total cholesterol, 0.73, 0.72, 0.72, 0.70 g/cm2, lowest to highest quartile, P for trend=0.02. Cholesterol levels in women and men from young adulthood to middle age years do not appear to have long-term clinical implications for osteoporosis later in life. |
| Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2'-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men Porkkala-Sarataho, E., J. T. Salonen, et al. (2000), Arterioscler Thromb Vasc Biol 20(9): 2087-93. Abstract: We studied the long-term effects of vitamins E and C and their combination on lipid peroxidation in vivo and in vitro. The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) trial is a double-masked placebo-controlled randomized clinical trial to study the effects of vitamin C (500 mg of slow release ascorbate per day), vitamin E (182 mg of RRR-alpha-tocopherol acetate per day), and the combination of both antioxidants. Lipid peroxidation measurements were carried out for 48 male participants at entry and at 12 and 36 months. Compared with placebo, vitamin E and the vitamin combination increased plasma lipid-standardized alpha-tocopherol during the first 12 months by 68.2% and 65.2% (P:<0. 001 for both), respectively, and reduced serum 7beta-hydroxycholesterol by 50.4% (P:=0.013) and 44.0% (P:=0.041), respectively. The net change of lipid standardized alpha-tocopherol was 63.8% after 36 months of vitamin E supplementation and 43.3% for the combination. Vitamin C supplementation elevated plasma total ascorbate level by 30.1% (P:=0.043) in 12 months and by 91.1% (P:=0. 001) in 36 months. Neither vitamin E, vitamin C, nor the combination influenced the urinary excretion rate of 7-hydro-8-oxo-2'-deoxyguanosine or the antioxidative capacity of plasma. Vitamin E and the combination of vitamins E and C enhanced the oxidation resistance of isolated lipoproteins and total serum lipids. Our data indicate that long-term supplementation of nondepleted men with a reasonable dose of vitamin E alone or in combination with slow release vitamin C reduces lipid peroxidation in vitro and in vivo, whereas a relatively high dose of vitamin C alone does not. |
| Long-term effects on cholesterol levels and the utilization of lipid-lowering drugs of a hospital-based programme for secondary prevention of coronary artery disease Stagmo, M., L. Westin, et al. (2001), J Cardiovasc Risk 8(4): 243-8. Abstract: BACKGROUND: The study was designed to determine whether a 1-year hospital-based secondary prevention programme would have any long-term effects on serum lipid levels and the use of lipid-lowering drugs in patients with coronary artery disease 4 years after referral to primary care facilities for follow-up. DESIGN/METHODS: After acute myocardial infarction or coronary bypass surgery, 241 consecutive patients were randomly assigned to conventional care (CC) by the primary health care facilities or to a 1-year hospital-based secondary prevention programme (SPP) with target levels for serum cholesterol (< 5.2 mmol/l) and triglycerides (< 1.5 mmol/l). After 1 year all patients were referred to the primary care sector for a further 4-year follow-up. RESULTS: At the 1-year follow-up there was a significant decrease in serum cholesterol, LDL-cholesterol and triglyceride levels in the SPP group but no change in the CC group, and lipid-lowering drugs were used more frequently in the SPP group. These changes were maintained after 5 years. The proportion of patients achieving target serum cholesterol and triglyceride levels were larger in the SPP group. CONCLUSIONS: Initiatives regarding cholesterol lowering and drug treatment taken by specialists within a structured hospital-based SPP have long-term impact. Accordingly, drug treatment should be initiated and adjusted to adequate doses before patients are referred to primary care for follow-up. |
| Long-term effects on clinical outcomes of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation in the post coronary artery bypass graft trial. Post CABG Investigators Knatterud, G. L., Y. Rosenberg, et al. (2000), Circulation 102(2): 157-65. Abstract: BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol (LDL-C) levels to <100 mg/dL compared with a moderate reduction to 132 to 136 mg/dL decreased the progression of atherosclerosis in grafts. Low-dose anticoagulation did not significantly affect progression. METHODS AND RESULTS: Approximately 3 years after the last trial visit, Clinical Center Coordinators contacted each patient by telephone to ascertain the occurrence of cardiovascular events and procedures. The National Death Index was used to ascertain vital status for patients who could not be contacted. Vital status was established for all but 3 of 1351 patients. Information on nonfatal events was available for 95% of surviving patients. A 30% reduction in revascularization procedures and 24% reduction in a composite clinical end point were observed in patients assigned to aggressive strategy compared with patients assigned to moderate strategy during 7.5 years of follow-up, P=0. 0006 and 0.001, respectively. Reductions of 35% in deaths and 31% in deaths or myocardial infarctions with low-dose anticoagulation compared with placebo were also observed, P=0.008 and 0.003, respectively. CONCLUSIONS:-The long-term clinical benefit observed during extended follow-up in patients assigned to the aggressive strategy is consistent with the angiographic findings of delayed atherosclerosis progression in grafts observed during the trial. The apparent long-term benefit of low-dose warfarin remains unexplained. |
| Long-term evaluation of extracorporeal shock-wave lithotripsy for cholesterol gallstones Tsumita, R., N. Sugiura, et al. (2001), J Gastroenterol Hepatol 16(1): 93-9. Abstract: BACKGROUND: Extracorporeal shock-wave lithotripsy (ESWL) is a treatment that preserves the gallbladder. Problems after ESWL treatment include stone recurrence and the development of biliary symptoms. METHODS: Two hundred and sixty-two patients with cholesterol-type gallstones, the best indication for ESWL treatment, and 42 control patients with cholesterol-type gallstones who received no treatment entered this study. We evaluated the factors associated with recurrence of gallstones after stone clearance and the development of biliary symptoms after ESWL treatment. RESULTS: The 3-, 5- and 7-year cumulative probabilities of gallstone recurrence were 20.6, 27.1 and 33.1%, respectively, with the recurrence probability significantly lower in patients with good gallbladder contractility. In patients with recurrence, ursodeoxycholic acid (UDCA) treatment was effective. In 69 patients with residual gallstones, the 3-, 5- and 7-year cumulative risks of biliary symptoms were 17.3, 24.9 and 30.5%, respectively. With residual gallstones, the risk of biliary symptoms developing was significantly lower in patients with a < or = 3 mm fragment size at the end of ESWL treatment and in those treated consistently with UDCA for 6 months or more after treatment with ESWL. The risk of biliary symptoms was significantly lower in ESWL-treated patients with residual stones who had a < or = 3 mm fragment size after treatment compared to those of control patients. CONCLUSIONS: Ursodeoxycholic acid was effective in clearing stones in patients with gallstone recurrence. In patients with residual stones, the fragmentation of stones to < or = 3 mm and UDCA administration effectively reduced the risk of subsequent biliary symptoms. |
| Long-term experience of quality assurance of cholesterol testing in a general practice surgery Fyffe, J. A. (1994), Ann Clin Biochem 31 (Pt 6): 568-9. |
| Long-term experience with extracorporeal low-density lipoprotein cholesterol removal by dextran sulfate cellulose adsorption Schulzeck, P., C. J. Olbricht, et al. (1992), Clin Investig 70(2): 99-104. Abstract: Patients with familial hypercholesterolemia have a high incidence of coronary heart disease due to diet- and drug-resistant, elevated low-density lipoprotein cholesterol (LDL-C). Five patients with familial hypercholesterolemia and diet- and drug-resistant LDL-C greater than 230 mg/dl were treated by LDL apheresis using dextran sulfate cellulose adsorption (Liposorber System LA-15, Kaneka). Plasma separation was by 0.5-m2 polysulfone hollow fiber filter. Two columns containing 150 ml of dextran sulfate cellulose alternately adsorbed LDL and were regenerated by 4.1% saline. The five patients received a total of 360 treatments at 7-day intervals. The treated plasma volume per session was 4.1 +/- 0.4 l. Postapheresis values compared with preapheresis were: total cholesterol, 40%; LDL-C, 28%; VLDL-C, 65%; HDL-C, 95%; triglycerides, 70%; white blood cells, 116%; platelets, 87%; C3 complement, 79%; fibrinogen, 64%; albumin, 94%. The decrease in HDL-C per treatment was not significant. The safety parameters showed only slight changes. The initial LDL of 436 +/- 172 mg/dl decreased to mean pre-apheresis levels of between 150 and 100 mg/dl. The anti-atherogenic HDL increased in three and remained unchanged in two patients. Adverse events like hypotension, angina pectoris, and technical problems occurred in 11 of the 360 treatments. Long-term treatment of patients with diet- and drug-resistant familial hypercholesterolemia by extracorporeal dextran sulfate cellulose adsorption is effective and safe. |
| Long-term feeding of casein or soy protein with or without cholesterol in Mongolian gerbils. I. Morphologic effects DiFrancesco, L., D. H. Percy, et al. (1990), Acta Cardiol 45(4): 257-71. Abstract: This study was designed to determine whether male Mongolian gerbils (Meriones unguiculatus) develop atherosclerosis (AS) during long-term feeding of diets similar to those consumed by humans. Gerbils were fed diets containing 16% casein (C) or soy (S) protein +/- 0.1% cholesterol (CH) for 15 months. The energy contribution from protein, fat and carbohydrate was similar to the energy distribution reported for the average North American (NA) diet and the level of added dietary CH resembled the average NA intake. At mo 0, 3, 6, 9, 12 and 15, animals were killed and tissue sections were prepared for histologic examination. Microscopic observations of cardiovascular tissues did not reveal any evidence of AS in any of the diet groups. Liver fatty infiltration (FI) was evident in the C+CH and C groups at mo 3 and 9, respectively, and continued to occur at all subsequent sampling times. Livers from gerbils fed S+CH also began to exhibit FI at mo 9, while livers from S-fed gerbils did not show any significant morphologic changes. Biochemical liver total lipid results supported the histological liver findings. Other tissues examined did not reveal any morphological changes related to diet. The gerbil may be a useful animal model to study mechanisms which inhibit AS development. |
| Long-term feeding of casein or soy protein with or without cholesterol in Mongolian gerbils. II. Plasma lipid and liver cholesterol responses DiFrancesco, L., O. B. Allen, et al. (1990), Acta Cardiol 45(4): 273-90. Abstract: Male Mongolian gerbils (Meriones unguiculatus) were fed casein or soy protein in the presence and absence of dietary cholesterol for 15 months. Diets resembled the average North American diet in energy contributions from protein, fat and carbohydrate, cholesterol content and fatty acid profile. At month 0, 3, 6, 9, 12 and 15, plasma samples were analyzed for total cholesterol (TC), HDL cholesterol (HDLC) and triglyceride (TG) concentrations. Plasma LDL cholesterol (LDLC) was estimated indirectly. Liver TC was also determined at these time points. Comparisons of protein source and cholesterol level were averaged over the 15 month period. Casein-fed gerbils had significantly higher plasma TC and TG levels and lower HDLC levels (as a percent of TC) compared to soy-fed animals, independent of the presence or absence of dietary cholesterol. LDLC was significantly elevated in casein-fed gerbils only when cholesterol was present in the diet. Elevations in plasma TC levels were reflected by elevations in liver TC. Despite plasma lipid elevations that are consistent with the development of atherosclerosis (AS) and coronary heart disease (CHD) in humans, hyperlipidemic gerbils do not develop AS. Further characterization of gerbil lipid metabolism responses to dietary alterations aimed at the prevention of CHD in humans is necessary to elucidate the mechanism for the gerbil's resistance to AS. |
| Long-term hemostatic effects of cholesterol-lowering therapy with atorvastatin Trifiletti, A., A. Lasco, et al. (2003), Pathophysiol Haemost Thromb 33(2): 84-7. Abstract: This study assessed hemostatic effects of an HMC-CoA reductase inhibitor, atorvastatin, on different parameters in 32 hypercholesterolemic patients of both sexes. In the patients and in 25 control subjects, plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor (PAI-1), D-dimer, prothrombin fragment 1 + 2 (F1 + 2), total cholesterol, triglycerides and fibrinogen had been measured. All these parameters were evaluated in patients after 6 and 12 months of treatment with atorvastatin at a dosage of 20 mg/day. This treatment significantly lowered the total cholesterol level in all patients. Moreover, after 6 months of atorvastatin treatment, PAI-1 and F1 + 2, which were both increased at baseline, were significantly reduced. This reduction continued after 12 months. The present results show that a reduction of hemostatic abnormalities, which exist in hypercholesterolemia, may be another important effect of the atorvastatin therapy. |
| Long-term impact of a community pharmacist intervention on cholesterol levels in patients at high risk for cardiovascular events: extended follow-up of the second study of cardiovascular risk intervention by pharmacists (SCRIP-plus) Yamada, C., J. A. Johnson, et al. (2005), Pharmacotherapy 25(1): 110-5. Abstract: STUDY OBJECTIVE: To determine the effect of a community pharmacist intervention in patients at high risk for coronary heart disease on low-density lipoprotein cholesterol (LDL) levels 1 year after completion of the Second Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP- plus). METHODS: Patients who completed the original study were invited to make a single return visit to their community pharmacy so that the pharmacist could measure their fasting LDL level using a point-of-care device. The primary outcome was change in LDL level from the 6-month (final) visit to the extended follow-up evaluation. RESULTS: Of the 359 patients who completed the original 6-month visit, data were collected for 162 (45%) patients. The mean +/- SD LDL level at completion of the original study was 107.9 +/- 33.6 mg/dl (2.79 +/- 0.96 mmol/L) (an increase of 2.7 mg/dl 0.07 mmol/L, 95% confidence interval -19.3-7.3 -0.5-0.19). Sixty-one (38%) patients were at the target LDL level (< 96.7 mg/dl < 2.50 mmol/L). CONCLUSION: The LDL reduction was maintained 1 year after completion of the extended follow-up. Since most patients were still not at the target LDL level, this finding suggests that continuing intervention is necessary to help patients reach this target. |
| Long-term intraindividual cholesterol variability: natural course and adverse impact on morbidity and mortality--the Framingham Study Kreger, B. E., P. M. Odell, et al. (1994), Am Heart J 127(6): 1607-14. Abstract: We examined intraindividual variability in serum TC in 2912 men and women having TC measured at each of biennial examinations 2 through 7 of the FHS. RMSE described variability around the linear slope of an individual's TC during the baseline decade. Average biennial difference +/- SD was +3.7 +/- 6.7 mg/dl in men, +6.6 +/- 8.8 mg/dl in women. RMSE was < 7 mg/dl in half the group, but in the teens and twenties in the highest quartile of variability. Age-adjusted analyses showed positive associations with all-cause mortality over a 24-year period in men and a positive relation to cardiovascular and coronary incidence and mortality in both sexes. Risk ratios for highest versus lowest quartile of TC variability ranged up to 1.75. High TC variability portends excess mortality risk, and women in particular must include TC variability among their risk factors for coronary death. |
| Long-term investigations of serum cholesterol, serum triglyceride, and HDL cholesterol in heritable hyperlipidemic rabbits Lind, B. M., R. Littbarski, et al. (1990), Z Versuchstierkd 33(6): 245-9. Abstract: The purpose of this investigation was to follow the course of the serum cholesterol, serum triglyceride and HDL cholesterol concentrations of heritable hyperlipidemic (HHL) rabbits (34 animals in total) in order to obtain an early prediction of these parameters, which appear to be highly associated with the presence of arteriosclerotic lesions. Measurements were done at 6-week intervals for one year, beginning at the 10th week of age. At week 10 the serum cholesterol concentration of females was 652.80 mg x dl-1 +/- 103.82 (standard deviation) and that of males was 648.84 mg x dl-1 +/- 146.04. The 10-week serum triglyceride concentration of males was 267.90 mg x dl-1 +/- 93.03, which decreased in two marked steps after week 10 and 40, while that of females was 246.70 mg x dl-1 +/- 67.51, which reached a maximum at 7 months and then decreased. Both the serum cholesterol and the serum triglyceride concentrations decreased significantly in males and females during the investigation period. The 10-week HDL cholesterol concentrations (males: 18.08 mg x dl-1 +/- 12.81; females: 14.61 mg x dl-1 +/- 8.56) remained relatively constant in both sexes during the investigation period. We consider one or two samplings, usually at weaning and at the beginning of an investigation, to ensure reliable biochemical parameters for the state of the animals. |
| Long-term low-dose treatment with reserpine of cholesterol-fed rabbits reduces cholesterol in plasma, non-high density lipoproteins and arterial walls Shafi, S., I. P. Stepanova, et al. (2002), J Cardiovasc Pharmacol 40(1): 67-79. Abstract: The effects of long-term low-dose treatment with reserpine on plasma lipoproteins and arterial cholesterol were determined in cholesterol-fed rabbits. Hepatic low-density lipoprotein (LDL) receptors; uptake of LDL by liver, heart, and kidneys; plasma fibrinogen; blood pressure; and heart rate were also determined. Reserpine at 43 microg/kg. d was continuously infused subcutaneously via implanted minipumps for 6 weeks into conscious unrestrained male New Zealand White rabbits (n = 5) fed a 0.2% cholesterol-enriched diet. Compared with controls, reserpine (n = 4) significantly reduced the elevated levels of plasma total cholesterol and esterified and unesterified cholesterol throughout the study, and at 6 weeks of treatment these reductions were 42, 41, and 49%, respectively. The increased cholesterol in the aortic walls (n = 5) produced by the atherogenic diet was reduced by 73% (p < 0.004) and 125I-tyramine cellobiose-labeled LDL by 67 to 86% (0.05 < p <0.004), respectively. The aortic intimal-medial thickness ratio was reduced by 70%. The decrease in elevated plasma total cholesterol was mainly due to cholesterol reductions in both LDL (41%) and non-high density lipoprotein (HDL) of density < 1.019 g/ml (51%). HDL cholesterol and triglyceride levels were unchanged. Reserpine had no significant effects on the clearance of 125I-tyramine cellobiose-LDL from plasma and there was a trend towards an increase in hepatic LDL receptor expression. Heart rate was decreased by 28%. There were no significant effects on blood pressure, liver and heart lipids, hematocrit, or plasma fibrinogen. The results suggest that treatment of cholesterol-fed rabbits with reserpine at a low dose over a long period prevents increases in plasma atherogenic lipoproteins. Reserpine decreases the cholesterol in aortic walls and the intima-media thickness ratio. This anti-atherosclerotic effect of reserpine may have therapeutic implication. |
| Long-term lowering of plasma cholesterol levels in LDL-receptor-deficient WHHL rabbits by gene therapy Kankkonen, H. M., E. Vahakangas, et al. (2004), Mol Ther 9(4): 548-56. Abstract: Lentiviral vectors encoding rabbit low-density lipoprotein receptor (LDLR) or green fluorescent protein (GFP) under the control of a liver-specific promoter (LSP) were used for intraportal gene transfer into the liver of hypercholesterolemic LDLR-deficient Watanabe Heritable Hyperlipidemic rabbits. In vitro cell culture analysis demonstrated functionality of the LSP-LDLR vector in mediating increased degradation of LDL in transduced liver cells. Twenty-five rabbits were each injected with 1 x 10(9) infectious virus particles into the portal vein. Liver biopsy samples were collected 4 weeks after the gene transfer and the rabbits were followed up for 2 years. Histological and RT-PCR analyses showed the expression of GFP and LDLR transgenes in the biopsy samples. Clinical chemistry and histological analyses revealed normal liver function and morphology during the 2-year follow-up with no safety issues. LSP-LDLR-treated rabbits demonstrated an average of 14 +/- 7% decrease in serum cholesterol levels during the first 4 weeks, 44 +/- 8% decrease at 1 year, and 34 +/- 10% decrease at the 2-year time point compared to the control rabbits. This study demonstrates the safety and potential benefits of the third-generation liver-specific lentiviral vectors in the treatment of familial hypercholesterolemia using direct intraportal liver gene therapy without the need for liver resection. |
| Long-term moderate sodium restriction does not adversely affect the serum HDL/total cholesterol ratio Geleijnse, J. M., J. C. Witteman, et al. (1995), J Hum Hypertens 9(12): 975-9. Abstract: We examined the effect of long-term moderate sodium restriction on the HDL/total cholesterol ratio within a randomised trial of the effect of mineral salt on blood pressure (BP). Eighty nine untreated hypertensive men and women aged 55-75 years were included in the analysis. During 24 weeks, 46 subjects used a low sodium, high potassium, high magnesium salt and 43 controls used common salt. Serum cholesterol levels were measured at baseline and at the end of the trial. After 24 weeks, 24 h urinary sodium was decreased by 41 mmol (95% Cl 23-60 mmol, P < 0.0001) in the mineral salt group compared with the controls. Serum total cholesterol was decreased in both groups, but 0.45 mmol/l (95% Cl 0.12-0.78, P = 0.01) more in the controls than in the mineral salt group after adjustment for age, sex and changes in body weight, serum total protein and potassium excretion. Serum HDL-cholesterol was decreased by 0.07 mmol/l in the controls and increased by 0.06 mmol/l in the mineral salt group, yielding a difference of 0.14 mmol/l (95% Cl 0.05-0.22 mmol/l, P = 0.003). The change in HDL/total cholesterol ratio was more favourable in the mineral salt group than in the controls (0.014 and 0.004 units, respectively, P = 0.014). We conclude that long-term moderate sodium restriction does not adversely affect the serum HDL/total cholesterol ratio and is a safe dietary measure for lowering BP. |
| Long-term predictors of subsequent cardiovascular events with coronary artery disease and 'desirable' levels of plasma total cholesterol Miller, M., A. Seidler, et al. (1992), Circulation 86(4): 1165-70. Abstract: BACKGROUND. Patients with coronary artery disease (CAD) are at considerable risk for subsequent cardiovascular events. Although hyperlipidemia accentuates the risk, predictors of subsequent events with CAD and desirable total cholesterol (TC) (less than 5.2 mmol/l) have not been assessed. METHODS AND RESULTS. A survival analysis was performed in a subset of 740 consecutive patients who underwent diagnostic coronary arteriography between 1977 and 1978. Eight-three men and 24 women with angiographically documented CAD and desirable TC were followed for subsequent cardiovascular events, including myocardial infarction and cardiovascular death. Over a 13-year period, 75% of CAD subjects with reduced high density lipoprotein cholesterol (HDL-C) (less than 0.9 mmol/l) developed a subsequent cardiovascular event compared with 45% of those with HDL-C greater than or equal to 0.9 mmol/l (p = 0.002). A Kaplan-Meier analysis revealed significantly greater survival from cardiovascular end points in patients with baseline levels of HDL-C greater than or equal to 0.9 mmol/l (p = 0.005). After 11 variables were tested, an age-adjusted Cox proportional-hazards model identified two pairs of independent predictors of subsequent cardiovascular events: they were a left ventricular ejection fraction (LVEF) less than 35% (relative risk RR, 6.5; 95% confidence interval CI, 2.8, 15.3; p less than 0.001) and reduced HDL-C (RR, 2.0; 95% CI, 1.2, 3.3; p = 0.01) in the first model and LVEF less than 35% (RR, 6.5; 95% CI, 2.7, 15.6; p less than 0.001) and TC:HDL ratio greater than or equal to 5.5 (RR, 1.9; 95% CI, 1.1, 3.1; p = 0.02) in the second model. CONCLUSIONS. Low HDL-C (or high TC:HDL-C) is strongly predictive of subsequent cardiovascular events in subjects with CAD, despite desirable TC. As such, identification of this potentially modifiable risk factor should be actively pursued in this high-risk subgroup. |