Ameliorative effect of statin therapy on oxidative damage in heart tissue of hypercholesterolemic rabbits

The aim of this study was to investigate the effects of a high‐cholesterol diet in the presence and absence of statin on Cu‐Zn‐superoxide dismutase (Cu,Zn‐SOD), malondialdehyde (MDA), protein carbonyl (PCO), and nitric oxide (NO) of blood and heart tissue, the antioxidant activity of serum paraoxonase‐1 (PON‐1), and on the blood lipid profile of rabbits. The animals were divided into four groups each of which included 10 rabbits. Rabbits in group 1 received a regular rabbit chow diet (normal diet) for 8 weeks; those in group 2 received atorvastatin (0.3 mg atorvastatin per day/kg body weight) for 8 weeks; those in group 3 received high‐cholesterol diet for 8 weeks; and those in group 4 received high‐cholesterol diet for 4 weeks, a high‐cholesterol diet + atorvastatin (0.3 mg atorvastatin per day/kg body weight) for 8 weeks. The parameters were measured by spectrophotometric methods. As expected, the atherogenic diet caused a pronounced increase in lipid profile (not HDL) parameters. Rabbits in group 3 showed higher PCO, MDA, and NO levels in circulating and heart tissue compared to the rabbits in group 1. Atorvastatin has prevented or limited LDL oxidation and has showed constitutively beneficial effects in group 4. Increased LDL‐C, PCO, MDA, and NO levels leading to decreasing PON‐1 activity thus create a predisposition to atherogenesis in this model. But atorvastatin administration partly ameliorated oxidative damage in heart injury of hypercholesterolemic rabbits. Atorvastatin which functions as a potent antioxidant agent may inhibit this LDL‐C oxidation by increasing PON‐1 activity in atherogenesis.     

A procedure for determining the oxidative modification of apolipoproteins in low-density lipoproteins

The purpose of the present study was to develop a new procedure for estimating the oxidative modification of apolipoproteins in low-density lipoproteins (LDLs). The procedure was developed to use blood serum from 153 males aged 45-65 years, including 69 patients with coronary angiography-verified coronary atherosclerosis and 84 males from a representative sample from Novosibirsk residents of the same age. The new procedure is as follows: a rapid method for isolating serum LDLs, their apolipoprotein (apoLP) protein measurement by the Lowry procedure, their precipitation, a reaction with 2,4-dinitrophenylhydrazine in 2 M HCl solution, by subsequently rinsing in the ethanol:ethyl acetate (1:1) solution, dissolving the precipitate in 8 M urea, and by determining the level of the resultant dinitrophenylhydrazones by spectrophotometry at 363 nm, followed by conversion to LDL concentration of apoLP. The procedure is of informative value for the degree of oxidative LDL modification of apoLP under oxidative stress; it is technically simple, takes little time, and shows a good reproducibility. The values of determined oxidized LDL apoLP by the developed procedure highly positively correlated with the estimates of an oxidized total blood protein fraction and with the values of endothelial dysfunction and did not with the parameters of blood LDL peroxidation. The detected elevated oxidation LDL apoLP in males with coronary atherosclerosis suggests that this index is an additional marker of potentially atherogenic LDL changes.     

Effects of two lipid-lowering,carotenoid-controlled diets on the oxidative modification of low-density lipoproteins in free-living humans

This study compares the effects of two lipid-lowering diets [a diet enriched in MUFAs (monounsaturated fatty acids) and a HCLF (high-carbohydrate/low-fat) diet] with a controlled carotenoid content on risk factors for coronary heart disease, including in vitro copper-induced LDL (low-density lipoprotein) oxidation and serum lipid levels. A randomized crossover dietary intervention study, with two diets each consumed for 14-16 days, was conducted in 18 women and 13 men aged 20-70 years, recruited via personal contacts and advertisements in newspapers. Both diets (MUFA-enriched diet and HCLF diet) contained the same basic foods and had a controlled carotenoid content, high in lycopene. The in vitro copper-induced oxidation of isolated LDL showed a longer lag phase (mean difference 7.4 min in women and 7.34 min in men) after the MUFA-enriched diet compared with the HCLF diet. Serum total cholesterol, LDL cholesterol and carotenoid levels were similar after the two diets. Serum triacylglycerol levels were significantly lower and those of HDL (high-density lipoprotein) cholesterol were significantly higher at the end of the MUFA-enriched diet compared with the HCLF diet. It is concluded that the significantly longer lag phase for oxidation of LDL, the higher HDL cholesterol level and the lower triacylglycerol level in subjects following a carotenoid-controlled, MUFA-enriched diet may decrease the risk of coronary heart disease.     

The effect of yogurt on acetaminophen absorption by activated charcoal and burnt toast

Although acetaminophen overdose can be treated with N-acetylcysteine, activated charcoal is useful in preventing absorption of acetaminophen from the gut. Mixing activated charcoal with yogurt may make the dose more palatable. We investigated effects of yogurt on absorption of acetaminophen by burnt toast or activated charcoal in intestinal fluid using an in vitro model. The aliquots of phosphate buffer saline (PBS) were supplemented with high concentrations of acetaminophen after adjusting the pH to 7.2 (to mimic intestinal fluid). Then specimens were treated with various dosages (15 mg/mL, 25 mg/mL, or 50 mg/mL) of activated charcoal or burnt toast. A small amount of fluid was withdrawn at 0, 5, 10, 20, and 30 min and acetaminophen concentrations were measured by the fluorescence polarization immunoassay (FPIA). We also treated other aliquots of PBS buffer containing acetaminophen with activated charcoal and yogurt or burnt toast and yogurt. Then small aliquots were withdrawn at specific time intervals to determine concentrations of acetaminophen. Activated charcoal was very effective in removing acetaminophen from intestinal fluids and the presence of yogurt insignificantly affected such absorptions. In contrast, burnt toast had a modest effect on removing acetaminophen from fluids but yogurt significantly increased the capability of burnt toast to absorb acetaminophen. However, the activated charcoal/yogurt combination is more effective than the burnt toast/yogurt combination for absorbing acetaminophen.     

Plasma lipid oxidation and susceptibility of low-density lipoproteins to oxidation in male patients with stable coronary artery disease

Objectives: Oxidative modifications of low-density lipoproteins (LDL) are considered to be important in the pathogenesis of atherosclerosis. However, the data on the association between LDL oxidation and severity of clinical manifestations of coronary artery disease (CAD) are contradictory. Previous reports were concerned mostly with unstable angina patients. The present study was undertaken to evaluate plasma lipid oxidation status in patients with stable CAD.

Design and Methods: 37 male patients with angiographically confirmed CAD (asymptomatic or suffering from stable angina pectoris) and 32 control subjects were used in the study. Plasma levels of vitamin E and products of lipid peroxidation, as well as parameters of the test for oxidizability of LDL in vitro were measured.

Results: We did not find differences between 2 groups of individuals regarding the levels of products of lipid peroxidation, vitamin E levels, lag time, maximal rate of oxidation, and total amount of conjugated dienes in the test for oxidizability of LDL.

Conclusion: The results of our study challenge, but do not disprove, the oxidative hypothesis of atherosclerosis. Real atherosclerotic modifications of plasma LDL occur apparently in the vascular wall after trapping of LDL by the interstitial matrix. The rise in oxidative parameters in unstable angina reported in the literature may not be the cause of the disease but, rather, the consequence of the multiple brief episodes of ischemia-reperfusion.     

Astaxanthin prevents changes in the activities of thioredoxin reductase and paraoxonase in hypercholesterolemic rabbits

This study explored the effects of the antioxidant astaxanthin on paraoxonase and thioredoxin reductase activities as well as on other oxidative stress parameters and on the lipid profile in hypercholesterolemic rabbits. Rabbits were fed a standard or a hypercholesterolemic diet alone or supplemented with 50, 100 and 500 mg/100 g of astaxanthin for 60 days. Antioxidant enzymes activities, lipid profile and oxidative stress markers were evaluated in the serum. The hypercholesterolemic diet increased lipids, including unsaturated fatty acids level, whereas it decreased saturated fatty acids level. These changes were accompanied by increased levels of oxidized low-density lipoprotein and oxidized low-density lipoprotein antibodies, as well as lipid and protein oxidation. Astaxanthin (100 and 500 mg/100 g) prevented hypercholesterolemia-induced protein oxidation, whereas 500 mg/100 g of astaxanthin decreased protein oxidation per se. The activities of superoxide dismutase and thioredoxin reductase were enhanced, whereas paraoxonase activity was inhibited in hypercholesterolemic rabbits. All astaxanthin doses prevented changes in thioredoxin reductase and paraoxonase activities. This effect was not related to a direct effect of astaxanthin on these enzymes, because in vitro astaxanthin enhanced thioredoxin reductase and had no effect on paraoxonase activity. Astaxanthin could be helpful in cardiovascular diseases by restoring thioredoxin reductase and paraoxonase activities.     

南通地区健康体检人群小而密低密度脂蛋白水平调查

目的 初步调查南通地区健康人群小而密LDL(胆固醇和蛋白质)的分布情况.方法 体格检查和实验窜检查均无异常的健康人群254名(男137名,女117名),按年龄分成20～29岁(65名)、30～39岁(65名)、40～49岁(46名)、50～69岁(35名)、和370岁(43名)5组.检测采用全自动生化分析仪和芯片电泳技术.结果 小而密LDL胆固醇和蛋白质水平均值为(0.39±0.14)mmol/L和(241±158)mg/L,小而密LDL胆固醇与总胆固醇、三酰甘油、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇相关性较好(r=0.67、0.35、-0.42和0.46,P均<0.01),小而密LDL蛋白质与这些血脂指标相关性较好(r=O.54、0.24、-0.32和0.52,P均<0.01).小而密LDL蛋白质和胆固醇水平随年龄增高呈上升趋势,而70岁以上人群呈下降趋势;男性小而密低密度脂蛋白水平高于女性[(0.40±0.11)mmol/L vs.(O.37±0.17)mmol/L,P<0.01;(253±59)mg/L vs.(237±95)mg/L,P<0.05],P相似文献   

Biochemical effects,hypolipidemic and anti-inflammatory activities of Artemisia vulgaris extract in hypercholesterolemic rats

The purpose of the present study was to investigate hypolipidemic and anti-inflammatory effects of Artemisia vulgaris extract in hypercholesterolemic rats. Hypercholesterolemia was induced by feeding of rats with high fat diet containing 3% cholesterol in olein oil, for 8 weeks. Feeding of rats with high fat diet for 8 weeks, leading to a significant increase in serum triglycerides, total cholesterol, low density lipoprotein cholesterol, malondialdehyde and nitric oxide, tumor necrosis factor-α levels and a significant decrease in serum high density lipoprotein cholesterol level, liver hydroxymethylglutaryl-CoA reductase activity and paraoxonase-1 activities as compared to the normal control group. Treatment of high fat diet rats with Artemisia vulgaris extract for 4 weeks at a dose of 100 mg/kg per day, resulted in normalized serum lipid profile, a significant increase in paraoxonase-1 activity and decrease in serum malondialdehyde, nitric oxide and tumor necrosis factor-α level as compared to high fat diet-treated animals. Also the extract caused a significant decrease in hydroxymethylglutaryl-CoA reductase activity as compared with both high fat diet-treated animals and control ones. In conclusion, Artemisia vulgaris extract has hypolipidemic, anti-inflammatory, antioxidant properties; it may serve as a source for the prevention of atherosclerosis and cardiovascular diseases.     

Effects of direct adsorption of lipoproteins apheresis on lipoproteins, low-density lipoprotein subtypes, and hemorheology in hypercholesterolemic patients with coronary artery disease.

Direct adsorption of lipoproteins (DALI) apheresis has been shown to reduce effectively low-density lipoprotein (LDL) cholesterol and lipoprotein (a) concentrations. However, the effects on nontraditional risk indicators such as hemorheology and LDL subtypes have not been investigated so far. Five patients (2 women, 3 men, age 53 +/- 8 years) with coronary artery disease and severe LDL hypercholesterolemia regularly treated with other LDL apheresis devices entered the study and were then treated with DALI for the first time. Hemorheological and lipoprotein parameters were measured before and immediately after the initial DALI apheresis as well as before the fourth DALI apheresis. Compared to baseline (before the first DALI apheresis), the following parameters were significantly improved (p < 0.05) after the first DALI apheresis: LDL cholesterol (69 +/- 28 versus 208 +/- 82 mg/dl) and cholesterol in each LDL subfraction as well as plasma viscosity (1.23 +/- 0.04 versus 1.37 +/- 0.06 mPa), C-reactive protein, native blood viscosity, red cell aggregation, and red cell deformability. When parameters before the fourth DALI apheresis were compared to baseline, LDL cholesterol was still lower, and red cell deformability was still improved while cholesterol in each subfraction showed a statistical trend to lower concentrations (0.08 < p < 0.14). In conclusion, DALI apheresis not only reduces LDL cholesterol but also induced a significant reduction of cholesterol in all LDL subfractions and improved various hemorheological parameters.     

Influence of acetaminophen on antipyrine kinetics in rats

Studies have suggested that acetaminophen may inhibit the liver metabolism of several drugs. Due to the expected clinical relevance of these findings, the present study was undertaken to examine acetaminophen effects on in vivo drug metabolism in the rat, using the model substrate antipyrine. Oral doses of 15 mg/kg acetaminophen were administered twice daily for 7 days. Antipyrine kinetics were determined before and immediately after acetaminophen treatment in rats (used as their own control). Acetaminophen treatment significantly increased antipyrine half-life by 29% and reduced its clearance by 24%, without affecting its volume of distribution. Further studies are warranted to determine the relevance and mechanism of these findings.     

胆红素预防兔实验性动脉粥样硬化形成的研究

目的通过兔实验性动脉粥样硬化(atherosclerosis,AS)试验探讨体内的强抗氧化剂—血清胆红素防止AS形成的作用及机制。方法在新西兰白兔食饵性AS模型上,观察胆红素治疗性给药对氧化低密度脂蛋白(oxidized low-density lipoprotein,ox-LDL)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)等水平变化及对主动脉壁粥样硬化斑块形成的影响。血清胆红素采用重氮法测定,ox-LDL采用ELISA法测定,TC、TG采用酶法测定,LDL-C采用Friedward公式计算。结果实验第43天,AS模型组的血清胆红素较正常对照组及胆红素处理组降低(P<0.05,P<0.01),胆红素处理组的ox- LDL较正常对照组增高但低于AS模型组(P<0.05,P<0.01),胆红素处理组与AS模型组的TC、TG、LDL-C等水平无显著差异(P>0.05)。结论胆红素在体内的浓度降低,致使体内抗氧化能力减弱,LDL-C氧化修饰形成ox-LDL增多,使细胞内大量脂质聚集形成泡沫细胞,导致AS形成。适当提高体内胆红素浓度以增加体内抗氧化能力,有利于抑制LDL-C氧化形成ox-LDL,防止泡沫细胞形成,可能是防治AS的又一重要途径。     

Oxidized low-density lipoprotein-induced expression of ABCA1 in blood monocytes precedes coronary atherosclerosis and is associated with plaque complexity in hypercholesterolemic pigs

BACKGROUND: Elevated oxidized low-density lipoprotein (oxLDL) is associated with atherosclerosis and high cardiovascular risk. Previously, we identified 18 genes in coronary plaque macrophages of hypercholesterolemic pigs that correlated with plaque oxLDL. OBJECTIVE: To determine which of these genes were differentially expressed in blood monocytes and correlated with blood and plaque oxLDL and with plaque complexity. METHODS: RNA expression in monocytes of 27 hypercholesterolemic and 12 control pigs was analyzed with quantitative real-time polymerase chain reaction. RESULTS: Five of 12 genes with detectable expression in monocytes were overexpressed (at P < 0.01 level) in blood monocytes of hypercholesterolemic pigs: ABCA1, SCD, IRF1, SDC2, and TLR2. ABCA1 RNA expression in blood monocytes correlated with blood oxLDL, and its RNA and protein expression was increased prior to atherosclerotic plaque formation. Higher expression of ABCA1 in monocytes was associated with higher plaque complexity and higher plaque oxLDL. Immunostaining of coronary plaques showed the association of ABCA1 with macrophages, lipids, and oxLDL; ABCA1 protein correlated with plaque oxLDL (R(2) = 0.66; P < 0.0001). In THP-1 monocytes, oxLDL induced ABCA1 expression. OxLDL-induced foam cell generation in THP-1 and human monocyte-derived macrophages was associated with a further increase of ABCA1 expression. CONCLUSIONS: The increase of ABCA1 in monocytes in association with blood oxLDL prior to atherosclerotic lesion formation and the association of higher ABCA1 with higher plaque complexity suggests that ABCA1 is an early biomarker of atherosclerosis. Studies in humans are warranted.     

The effect of selective low-density lipoprotein apheresis on plasma lipoperoxides and antioxidant vitamins in familial hypercholesterolemic patients.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by a lifelong elevation in the concentration of low-density lipoprotein (LDL) bound cholesterol in blood by cholesterol deposits and by early coronary artery disease. The LDL apheresis technique has been introduced with the goal of reducing LDL cholesterol levels, thereby preventing the development of atherosclerosis. The literature on LDL apheresis reports 2 different facets, the therapeutic aspect associated with the lessening of LDL concentration and the initiation of a peroxidation process associated with the biocompatibility of the artificial membrane. Lipid and protein peroxidation gives rise to toxic and atherogenic hydroperoxide, mostly lipid hydroperoxides, and derivative compounds, which may offset the benefit of the procedure. In this paper, plasma hydroperoxide levels are determined along with the elevation of the serum and LDL antioxidant status in hypercholesterolemic patients before and following repeated LDL apheresis sessions. Hydroperoxide concentration has been expressed both in terms of plasma volume and LDL concentration. A highly significant increase in LDL lipid hydroperoxides is demonstrated when expressed in terms of LDL concentration and is associated with the LDL apheresis procedure. The usefulness of antioxidant supplementation in LDL apheresis is discussed.     

甲壳质医用敷料对兔深Ⅱ度烧伤创面愈合的影响

目的探讨外用甲壳质医用敷料对兔深Ⅱ度烧伤创面愈合的影响。方法采用兔深Ⅱ度烧伤模型,创面外用甲壳质敷料,通过伤后不同时相点创面取材,检测羟脯氨酸(OHP)、细胞周期、创面愈合时间及组织病理形态学改变,以外用凡士林组作对照,观察甲壳质对兔深Ⅱ度烫伤创面愈合的影响。结果甲壳质组创面OHP含量及S期细胞百分明显高于凡士林组;创面愈合时间,甲壳质组优于凡士林组(P<0.05),提示甲壳质对促进创面愈合有帮助。病理形态提示甲壳质组上皮细胞和成纤维细胞增殖良好。结论甲壳质有明显的促进创面愈合作用,局部OHP含量增高,S期细胞百分比升高,创面愈合时间缩短。     

Effects of naloxone and flumazenil on antinociceptive action of acetaminophen in rats

Background: Studies of acetaminophen suggest that multiple nociceptive pathways are involved in the drug's analgesic action.Objective: The purpose of this study was to determine whether naloxone and flumazenil were able to modify or antagonize the antinociceptive effect of acetaminophen in rats.Methods: Adult albino Wistar rats were used in the study and randomly allocated to 1 of 4 groups. The acetaminophen group (A group) was administered IP saline and then 300 mg/kg IP acetaminophen 5 minutes thereafter. The acetaminophen + naloxone group (AN group) was pretreated with 1 mg/kg IP naloxone, followed by 300 mg/kg IP acetaminophen 5 minutes later. The acetaminophen + flumazenil group (AF group) was pretreated with 1 mg/kg IP flumazenil, followed by 300 mg/kg IP acetaminophen 5 minutes later. The control group received 2.5 mL IP saline, followed by an additional 2.5 mL IP injection of saline 5 minutes later. The paw-withdrawal latency period of the rats was assessed by an investigator blinded to treatment using the hot-plate test at 30, 45, 60, and 90 minutes after administration of acetaminophen.Results: Thirty-two rats were evenly randomized by envelope method into 4 groups of 8 rats each. Baseline values for the A, AN, AF, and control groups were not significantly different (9.1 [2.3], 10.5 [2.7], 9.8 [3.0], and 8.9 [1.4] sec, respectively). In the AF group, flumazenil appeared to antagonize the analgesic effect exerted by the acetaminophen in the hot-plate test (30 min, 10.3 [3.7] sec; 45 min, 11.7 [5.1] sec; 60 min, 12.1 [5.1] sec; and 90 min, 12.2 [4.9] sec) and values were not significantly different from those obtained in the control group (30 min, 9.8 [2.2] sec; 45 min, 9.0 [1.6] sec; 60 min, 9.2 [1.6] sec; and 90 min, 8.5 [2.0] sec). In the AN group, naloxone did not significantly affect the values observed in the hot-plate test (30 min, 18.0 [4.5] sec; 45 min, 21.5 [7.8] sec; 60 min, 20.5 [5.9] sec; and 90 min, 22.3 [7.4] sec) and values at all time points were not significantly different from those obtained in the A group (30 min, 17.8 [7.6] sec; 45 min, 20.9 [6.9] sec; 60 min, 21.5 [7.3] sec; and 90 min, 23.8 [8.6] sec). All postbaseline values in the A and AN groups were significantly increased versus baseline and versus the control group values (all, P < 0.05). All postbaseline values in the A group were significantly greater than those in the AF group (all, P < 0.05).Conclusion: Flumazenil antagonized the analgesic effect exerted by acetaminophen, while naloxone had no significant effect on acetaminophen's antinociceptive action in this pain model in rats.     

Effects of simvastatin on blood pressure in hypercholesterolemic patients: An open-label study in patients with hypertension or normotension

Background

Simvastatin has been reported to improve endotheliumdependent vascular relaxation in patients with hypercholesterolemia. The consequent decrease in arterial stiffness might be associated with a decrease in blood pressure (BP).

Objective

The aim of this study was to determine whether simvastatin 20 and 40 mg/d have an effect on systolic and diastolic blood pressure (SBP and DBP, respectively) in patients with hypercholesterolemia, and, if so, whether the effect is dose dependent and/or is related to the changes in the serum lipid profile.

Methods

This 6-month, open-label study was conducted at the Lipid Clinics of the Department of Internal Medicine, University of Milan, Maggiore Hospital IRCCS, and of the Department of Internal Medicine 1, G. Salvini Hospital, Garbagnate Milanese (Milan, Italy). Patients aged 18 to 80 years with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet for >2 months before the study were enrolled. Patients at high risk for cardiovascular disease (CVD), according to the National Cholesterol Education Program Adult Treatment Panel II guidelines, were given simvastatin 20 mg (tablet) QD for 3 months, and those at low risk for CVD continued with diet only for 3 months (controls). Efficacy variables included body weight, SBP, DBP, and serum lipid levels (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C], and triglycerides [TG]). At 3 months, patients in the simvastatin + diet group who reached their therapeutic goal continued to receive simvastatin 20 mg/d for 3 additional months. In simvastatintreated patients who were normotensive at baseline or who became normotensive at 3 months but who did not reach the therapeutic goal, the simvastatin dosage was increased to 40 mg/d. Patients in both groups who remained hypertensive at 3 months were switched to hypotensive therapy. In the diet-only group, patients who were formerly normotensive or who became normotensive at 3 months but who did not reach their therapeutic goal continued with diet only or started lipid-lowering therapy. All other patients in the diet-only group continued to be treated with diet only, for 3 additional months. Efficacy variables were measured again at 6 months. Tolerability of simvastatin was assessed at each visit using patient interview and measurement of serum aminotransferase and creatine phosphokinase levels.

Results

The study population comprised 222 patients (132 women, 90 men; mean [SEM] age, 53.9 [0.95] years [range, 23-76 years]); 115 high-risk patients (57 with untreated stage 1 hypertension) were assigned to the simvastatin + diet group, and 107 low-risk patients (29 with untreated stage 1 hypertension) were assigned to the diet-only group. In the simvastatin group, after 3 months of therapy, mean SBP was decreased by 3.9 (1.49) mm Hg (change, −2.9%), mean DBP decreased by 3.0 (0.87) mm Hg (change, −3.7%), mean TC decreased by 90.6 (3.98) mg/dL (change, −27.0%), mean LDL-C decreased by 88.9 (3.88) mg/dL (change, −35.6%), and mean TG decreased by 26.3 (7.34) mg/dL (change, −15.8%) (all, P < 0.001). Mean HDL-C increased by 3.6 (1.16) mg/dL (change, 6.9%; P < 0.001). The BP-lowering effect was found only in patients with hypertension at baseline (n = 57); in these patients, mean SBP decreased by 7.2 (2.44) mm Hg (change, −4.8%; P < 0.005 vs baseline) and DBP decreased by 4.8 (1.29) mm Hg (change, −5.6%; P < 0.001 vs baseline). Also in the simvastatin group, 26 patients (22.6%) achieved their target SBP/DBP. In patients with normotension at baseline (n = 58), neither SBP nor DBP was changed significantly (changes, −0.8 [1.65] and −1.4 [1.15] mm Hg, respectively [−0.6% and −1.8%, respectively]). The changes in serum lipid levels were similar between hypertensive and normotensive patients in the simvastatin group. Forty-one patients (18 hypertensive and 23 normotensive at baseline) were treated with simvastatin 40 mg/d plus diet between months 3 and 6. At 6 months, no further significant decrease was observed in mean BP. In contrast, the expected dose-dependent response was observed for TC and LDL-C levels. In the diet-only group, no significant changes occurred in BP or serum lipid levels. Changes in BP, TC, LDL-C, TG, and HDL-C were significantly greater in the simvastatin + diet group than in the diet-only group (all, P < 0.001). Body weight did not change significantly in either group.

Conclusions

In this group of patients with hypercholesterolemia, the starting dosage of simvastatin (20 mg/d) was associated with reductions in SBP and DBP within 3 months of treatment in patients with hypertension, and this effect was independent of the lipid-lowering properties of the drug. Although the decrease in BP was modest, it is likely clinically relevant. Further studies on this topic are advisable.