Nitrite plasma levels in normolipemic and hypercholesterolemic patients with peripheral occlusive arteriopathy

BACKGROUND: The authors studied the nitrite plasma levels in a group of patients with peripheral obstructive arteriopathy. METHODS: The series consisted of 63 subjects (43 males, 20 females, mean age 64 +/- 9 years) suffering from peripheral arterial occlusive disease of the lower limbs, at II (55 cases) and III (8 cases) Fontaine stage; 21 subjects with total cholesterol (TC) lower than 200 mg/dl were considered as normolipemics, 24 subjects with TC values between 200 and 240 as mild hypercholesterolemics, 18 subjects with TC above 240 mg/dl as severe hypercholesterolemics. For each subject the determination of nitrite plasma levels was carried out, by the Gutman and Hollywood colorimetric method. RESULTS: In the normolipemic arteriopathics the basal value of nitrites was sharply reduced (p < 0.05) compared to the controls; in the mild hypercholesterolemics the mean basal value of nitrites was markedly higher compared to the controls; in the severe hypercholesterolemics the mean basal value of nitrites was statistically (p < 0.05) higher than that of the controls. In the arteriopathic patients, globally considered, the mean basal value of nitrites was superimposable on that of the normal control subjects. CONCLUSIONS: This study, carried out on the nitrite plasma levels in a group of arteriopathic patients allowed us to show the enhanced levels of nitric oxide due to the increase of LDL; this effect, previously observed in hypercholesterolemic diabetic and coronaropathic patients, leads us to the hypothesis of a stimulating effect of LDL upon NO endothelial synthesis; this would be a compensatory response to the damaging and vasoconstricting action of LDL.     

Nitrite plasma levels after an oral fat meal in normolipemic subjects

BACKGROUND: The authors, investigating the effects of an oral triglyceride-rich fatty load upon the endothelial function as regards the production of nitric oxide, performed the determination of plasma nitrites, which are stable, specific and irreversible end-products of nitric oxide. METHODS: The series consists of 13 metabolically normal female subjects (mean age 55 +/- 7 years); after an overnight fasting each subject undertook an oral fat load (butter 1 g/kg); a venous blood withdrawal was carried out before oral fat meal and after two and four hours. For each plasma sample total cholesterol, HDL-cholesterol and triglyceride plasma levels were determined by enzymatic methods; LDL-cholesterol was calculated by Friedwald's formula; the nitrite plasma levels were obtained by the Gutman and Hollywood colorimetric method. RESULTS: Total cholesterol, HDL-cholesterol, LDL-cholesterol did not show significant changes after the oral fat load; triglycerides rose significantly (p < 0.05) after 4 hours as compared to the basal value (226 +/- 12 vs 175 +/- 12 mg/dl, +30%). The nitrite plasma levels were almost unchanged before oral fat load and after 2 and 4 hours. CONCLUSIONS: The results suggest that the acute biochemical stress consisting of increased triglyceride-rich very low density lipoproteins was not able to stimulate the endothelial production of nitric oxide.     

Nitrite plasma levels in chronic lung disease patients

BACKGROUND: The authors carried out a study in a group of lung disease patients, about the behaviour of the plasmatic levels of nitrites (stable, specific and irreversible end-products of nitric oxide). METHODS: The series consisted of 13 male patients (mean age 65 +/- 7 years) with chronic obstructive pulmonary disease with type 1 respiratory failure; 33 male subjects (mean age 58 +/- 5 years) without internistic disease were considered as controls. For each subject the determination of nitrite plasma levels by the Gutman and Hollywood method based on the Griess colorimetric reaction was performed. RESULTS: The mean value of the plasmatic nitrites was significantly reduced (p < 0.05) as compared to the controls (11 +/- 0.48 mumol/l vs 21 +/- 0.92 mumol/l). CONCLUSIONS: The authors hypothesized that in chronic lung disease patients there would be a condition of initial pulmonary hypertension; in this condition long-term endothelium-dependent nitric oxide production, aimed at the vasodilating effects with secondary excessive exhaled amount of NO, might cause a reduction in nitrite plasma levels. These levels may represent an early marker of pulmonary hypertension and suggest interesting therapeutic treatments through inhalation of exogenous NO.     

Flaxseed reduces plasma cholesterol levels in hypercholesterolemic mouse models

OBJECTIVE: We examined the effects of whole ground flaxseed added to a Western diet on plasma and hepatic lipids and hepatic gene expression in male and female human apolipoprotein B-100 transgenic (hApoBtg) mice which have a plasma lipid profile more closely resembling man than wild type mice and in mice lacking the low density lipoprotein receptor (LDLr) and apolipoprotein B mRNA editing enzyme complex 1 (LDLr(-/-)/apobec(-/-)). METHODS: The Westernized control diet containing 0.1% cholesterol and 30% kcal as fat was fed for 10 days to hApoBtg mice and for 14 days to LDLr(-/-)/apobec(-/-) mice. Animals from each genetic background were then divided into 2 groups based on gender and mean plasma total cholesterol (TC). The hApoBtg and LDLr(-/-)/apobec(-/-) mice either continued on the control diet for a total of 31 and 35 days, respectively or were fed 20% w/w whole ground flaxseed (flax) with comparable caloric, macronutrient and fiber content for 21 days. Blood was obtained after a 4 hour fast from all mice prior to feeding both control and flax diets, after 10 days on the flax diet, and after 21 days on the flax at which time all mice were exsanguinated. RESULTS: The control diet increased TC by >100 mg/dl in the hApoBtg with a greater increase observed in males and by 800 mg/dl in mice lacking the LDLr. After 3 weeks, the flax diet significantly reduced plasma TC by 19% and 22% in hApoBtg and LDLr(-/-)/apobec(-/-), respectively and non-high density lipoprotein cholesterol (non-HDL-C) by 24% in both models (p for all <0.05). Flax significantly reduced hepatic cholesterol in hApoBtg by 32% and 47% in males and females, respectively and LDLr(-/-)/apobec(-/-) mice by 66%. Flax had no effect on the expression of the following hepatic genes: LDLr, 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, phospholipid transfer protein, cholesterol 7alpha hydroxylase, fatty acid synthase, and acyl CoA oxidase in either mouse model. CONCLUSIONS: Flaxseed reduces plasma and hepatic cholesterol in hApoBtg mice, but had no effect on hepatic lipogenic genes and was equally effective in mice lacking LDLr. The combined data suggest that the lipid lowering effect of flax is not hepatic mediated and may be at the level of cholesterol absorption and/or bile acid reabsorption.     

Effect of lipid-lowering and anti-hypertensive drugs on plasma homocysteine levels

Elevated plasma concentrations of homocysteine, a sulfur-containing amino acid, are a risk factor for coronary, cerebral and peripheral artery disease. Next to other factors, drugs used for the prevention or treatment of cardiovascular disease may modulate plasma homocysteine levels. Thus, a drug induced homocysteine increase may counteract the desired cardioprotective effect. The aim is to summarize the current knowledge on the effect of two important classes of drugs, lipid-lowering drugs and anti-hypertensive drugs, on homocysteine metabolism. Among the lipid-lowering drugs, especially the fibric acid derivatives, which are used for treatment of hypertriglyceridemia and low HDL-cholesterol, are associated with an increase of homocysteine by 20%-50%. This increase can be reduced, but not totally avoided by the addition of folic acid, vitamin B12 and B6 to fibrates. HMG-CoA reductase inhibitors (statins) do not influence homocysteine concentrations substantially. The effects of nicotinic acid and n3-fatty acids on the homocysteine concentrations are less clear, more studies are necessary to clarify their influence on homocysteine. Antihypertensive drugs have also been studied with respect to homocysteine metabolism. A homocysteine increase has been shown after treatment with hydrochlorothiazide, a lowering was observed after treatment with beta-blockers, but no effect with ACE-inhibitors. The clinical significance of the homocysteine elevation by fibrates and thiazides is not clear. However, individual patients use these drugs for long time, indicating that even moderate increases may be important.     

Oat bran lowers plasma cholesterol levels in mildly hypercholesterolemic men.

The effects of oat bran and wheat bran on plasma lipid concentrations were compared in a crossover study. Each bran (123 g oat bran or 54 g wheat bran) added nearly 18 g of nonstarch polysaccharide to a background diet containing about 10 g nonstarch polysaccharide. Twenty-three men (average plasma cholesterol level = 5.84 mmol/L, and low-density-lipoprotein (LDL) cholesterol level = 4.11 mmol/L) were randomly assigned to either the oat or wheat bran diet for 4 weeks and then changed to the alternate bran diet for a similar period. The oat bran diet produced significantly lower levels of plasma total cholesterol and LDL cholesterol: 5.65 +/- 0.16 and 3.88 +/- 0.15 mmol/L (mean +/- standard error) for oat bran vs 5.89 +/- 0.16 and 4.11 +/- 0.16 mmol/L for wheat bran. Food intake diaries showed that average consumption of total fat and saturated fat was identical during the two test periods, which excluded displacement of fat as an explanation for lowering of plasma cholesterol by oat bran. Our results indicate that in mildly hypercholesterolemic men, a diet high in soluble oat fiber can significantly lower plasma total cholesterol and LDL cholesterol and thus potentially lower the risk of coronary heart disease.     

Macadamia nut consumption lowers plasma total and LDL cholesterol levels in hypercholesterolemic men

This study was conducted to assess the cholesterol-lowering potential of macadamia nuts. Seventeen hypercholesterolemic men (mean age 54 y) were given macadamia nuts (40-90 g/d), equivalent to 15% energy intake, for 4 wk. Plasma total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and homocysteine concentrations and the fatty acid composition of plasma lipids were determined before and after treatment. Plasma MUFA 16:1(n-7), 18:1(n-7) and 20:1(n-9) were elevated after intervention with macadamia nuts. Plasma (n-6) and (n-3) PUFA concentrations were unaffected by macadamia nut consumption. Plasma total cholesterol and LDL cholesterol concentrations decreased by 3.0 and 5.3%, respectively, and HDL cholesterol levels increased by 7.9% in hypercholesterolemic men after macadamia nut consumption. Plasma triglyceride and homocysteine concentrations were not affected by treatment. Macadamia nut consumption was associated with a significant increase in the relative intake of MUFA and a reduced relative intake of saturated fatty acids and PUFA. This study demonstrates that macadamia nut consumption as part of a healthy diet favorably modifies the plasma lipid profile in hypercholesterolemic men despite their diet being high in fat.     

180例高胆固醇血症患者调脂治疗现状调查

目的 了解高胆固醇血症患者经调脂治疗后，达到国内《血脂异常防治建议》要求的总胆固醇与低密底脂蛋白胆固醇治疗目标的比例。方法 选择已接受同一调脂药物治疗至少2个月的高胆固醇血症患者，测定其血脂水平，判断是否达到治疗目标。同时记录患者的心血管病危险因子以及调脂治疗的药名称。结果 共入选180例患者，平均年龄65.8岁。其中6.7%的患者无危险因子也无明确的动脉粥样硬化疾病（低危组），65.5%的患者有危险因子但无明确的动脉粥样硬化疾病（高危组），27.8%的患者有明确的动脉粥样硬化疾病或糖尿病。在整个人群中，仅有44%的患者的总胆固醇与低密底脂蛋白胆固醇水平同时达到治疗目标。低危组与高危组患者的达标率高于动脉粥样硬化疾病与糖尿病组对。对4组不同调脂药物与达标率的关系也进行了研究：辛伐他汀组为51.8%，普伐他汀组为42.9%，氟伐他汀组为31.6%，其他药物组为12.5%。结论 超过一半正在接受调脂治疗的患者，其总胆固醇与低密度脂蛋白胆固醇水平并未达到治疗目标。调查表明在《血脂异常防治建议》与临床实践之间仍然存在一定差距，提示需要更积极的调脂治疗。     

Quantification of plasma cholesterol and triglyceride levels in hypercholesterolemic subjects receiving ascorbic acid supplements.

In order to assess the possible effects of ascorbic acid on plasma cholesterol and triglyceride levels and plasma lipoprotein composition, nine hypercholesterolemic subjects were treated with oral ascorbic acid (4 g/day) for 2 months. The data demonstrate: 1) no significant change in plasma cholesterol or triglyceride levels; 2) no significant change in the cholesterol or triglyceride concentrations of the major lipoprotein classes; and 3) the unexpected appearance of extra pre-beta bands on lipoprotein electrophoresis by the end of the ascorbic acid treatment period.     

Enhancing drug compliance in lipid-lowering treatment

Hyperlipidemia and the atherosclerotic conditions that result from it are well recognized as major contributors to coronary heart disease (CHD). Fortunately, several large-scale clinical trials have shown that there are effective treatments that can substantially lower atherogenic lipid levels and thereby reduce the risk of CHD mortality and morbidity. However, duplication of these dramatic trial results can be negatively affected in "real life" clinical practice by an important issue: compliance. No medications will work if patients do not take them. Unfortunately, patients who need lipid-lowering therapy are likely to need it long-term, perhaps for a lifetime. Yet, many do not adhere to the prescribed medication regimen. This article reviews some major studies of compliance for lipid-lowering drugs. The reasons why patients do not take them as prescribed vary: poor education, lack of understanding, cost, provider indifference, and others. Achieving compliance requires a multifaceted approach. It can be enhanced by encouraging patients to talk openly about their medication habits and by convincing them of the long-term benefits of reaching and maintaining target low-density lipoprotein cholesterol levels. Although more studies focusing on compliance specifically regarding CHD are needed, the current literature does provide some guidance. Arch Fam Med. 2000;9:1169-1175     

Effects of two "lipid-lowering" diets on plasma lipid levels of patients with peripheral vascular disease

Fifty subjects with peripheral vascular disease were randomly assigned to either the American Heart Association Hyperlipidemia Diet C (AHA, N = 23) or a higher fiber, low fat diet based on the Pritikin maintenance diet (HFD, N = 27) and studied for a 12-month period. Diet counseling was provided, and the subjects were encouraged to exercise regularly, to decrease their consumption of salt, alcohol, and caffeine, and to restrict cigarettes as much as possible. Dietary intake data showed that energy distribution was approximately 49% and 64% carbohydrate, 20% and 22% protein, and 31% and 14% fat for the AHA and HFD groups, respectively. Cholesterol and dietary fiber intakes averaged 201 mg and 23 gm per day, respectively, for the AHA group and 108 mg and 43 gm per day, respectively, for the HFD group. Generally, both groups showed tendencies toward decreased serum triglycerides, cholesterol, and LDL cholesterol and increased HDL cholesterol. The HFD group achieved a significant decrease in serum cholesterol (at month 12) (p less than .01). The only significant between-group difference was in serum cholesterol at 4 months (p less than .01), with the lower value in the HFD group. There was a consistent negative correlation between dietary fiber and serum cholesterol levels (p less than .01). Average weight loss was 4.1 kg for the AHA group and 6 kg for the HFD group. We concluded that both dietary regimens, combined with exercise, can be of benefit to patients with peripheral vascular disease.     

Plasma lipids and lipoproteins in hypercholesterolemic men fed a lipid-lowering diet containing lean beef,lean fish,or poultry

BACKGROUND: To reach desirable lipid and lipoprotein concentrations, patients with hypercholesterolemia are often told to replace the consumption of beef with that of fish and poultry. OBJECTIVE: The objective of this study was to compare the effects on lipoprotein profiles in hypercholesterolemic men of the incorporation of lean beef, poultry (without skin), and lean fish into an American Heart Association diet with a high polyunsaturated-to-saturated fatty acid ratio and a high fiber content. DESIGN: Three groups of subjects each rotated in a crossover design through 3 experimental periods that lasted 26 d each. The diets were planned to provide 11 713 kJ/d, of which 18% came from protein, 53% from carbohydrate, and 30% from lipids (polyunsaturated-to-monounsaturated-to-saturated fatty acid ratio: 1.0:1.1:1.0); 268 mg cholesterol/d; and 29 g fiber/d. RESULTS: The lean beef, lean fish, and poultry diets reduced plasma total and LDL cholesterol by 5-9%, LDL apolipoprotein B by 16-19%, VLDL triacylglycerols by 22-31%, and the ratio of total cholesterol to HDL cholesterol by 6-11%; they also increased the ratio of LDL cholesterol to apolipoprotein B by 18-28%. No significant difference was found in these lipid variables between the 3 experimental diets. However, the lean fish diet increased HDL(2) cholesterol significantly more (P < 0.05) than did the lean beef diet and the ratio of HDL(2) to HDL(3) cholesterol significantly more (P < 0.05) than did the lean beef and poultry diets. CONCLUSION: The results indicate that an American Heart Association diet with a high polyunsaturated-to-saturated fatty acid ratio and high fiber content induced numerous favorable changes in coronary artery disease risk factors in hypercholesterolemic men, regardless of the protein source.     

Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women

BACKGROUND: Soy-protein consumption is known to reduce plasma total and LDL cholesterol concentrations. However, the responsible soy component or components and the magnitude of effects in normocholesterolemic and mildly hypercholesterolemic subjects are unclear. OBJECTIVE: The present study examined the effects of soy isoflavone consumption on plasma concentrations of triacylglycerol, apolipoprotein (apo) A-I, apo B, lipoprotein(a), and total, LDL, and HDL cholesterol and on LDL peak particle diameter in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. DESIGN: In a randomized crossover trial, fasting plasma samples were obtained from 18 postmenopausal women throughout three 93-d periods of daily isolated soy protein (ISP) consumption providing an average of 7.1 +/- 1.1 (control), 65 +/- 11 (low isoflavone), or 132 +/- 22 (high isoflavone) mg isoflavones/d. RESULTS: Compared with values measured during the control diet, the plasma LDL cholesterol concentration was 6.5% lower (P < 0.02) during the high-isoflavone diet and the ratio of LDL to HDL cholesterol was 8.5% and 7.7% lower during the low- and high-isoflavone diets, respectively (P < 0.02). Isoflavone consumption did not significantly affect plasma concentrations of total or HDL cholesterol, triacylglycerol, apo A-I, apo B, or lipoprotein(a) or the LDL peak particle diameter. CONCLUSIONS: Consumption of isoflavones as a constituent of ISP resulted in small but significant improvements in the lipid profile in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Although the effects were small, it is possible that isoflavones may contribute to a lower risk of coronary heart disease if consumed over many years in conjunction with other lipid-lowering strategies.     

Low arginine plasma levels in patients after thoracoabdominal aortic surgery

OBJECTIVE: Thoracoabdominal aortic surgery is a high-risk procedure and associated with a significant morbidity and mortality. Ischemia reperfusion of visceral organs and lower extremities is one of the most important determinants of this morbidity. Arginine is the precursor of nitric oxide and arginine plasma levels are important in maintaining organ blood flow. Furthermore, arginine is important in wound healing and the immune system. Because of increased utilization of arginine, low arginine plasma levels could be expected after thoracoabdominal aortic surgery. We therefore measured arginine plasma levels in these patients. DESIGN: Six patients with thoracoabdominal aortic aneurysm were included in this study. SETTING: University Hospital Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands. SUBJECTS: Six patients undergoing thoracoabdominal aortic surgery. INTERVENTION: Plasma levels of arginine were measured by high-performance liquid chromatography. RESULTS: Very low arginine plasma levels were seen on the first postoperative day. From day 1 arginine slowly increased, but did not reach normal plasma levels on day 6. CONCLUSIONS: A significant decrease of arginine plasma levels was found and because of the fact that arginine has multiple functions, it may be important to keep these arginine plasma levels at normal or even higher levels in patients undergoing major vascular surgery. European Journal of Clinical Nutrition (2000) 54, 615-617.     

Plant sterols and endurance training combine to favorably alter plasma lipid profiles in previously sedentary hypercholesterolemic adults after 8 wk

BACKGROUND: Plant sterol supplementation was shown to reduce total and LDL-cholesterol concentrations, whereas endurance training was shown to increase HDL-cholesterol concentrations and decrease triacylglycerol concentrations. OBJECTIVE: The objective was to examine the effect of plant sterols, endurance training, and the combination of plant sterols and endurance training on plasma lipid and lipoprotein cholesterol concentrations, sterol concentrations, and cholesterol precursor concentrations in previously sedentary hypercholesterolemic adults. DESIGN: In an 8-wk, placebo-controlled, parallel-arm clinical trial, 84 subjects were randomly assigned to receive 1 of 4 interventions: 1) combination of sterols and exercise, 2) exercise, 3) sterols, or 4) control treatment. RESULTS: Sterol supplementation significantly (P < 0.01) decreased total cholesterol concentrations by 8.2% from baseline. In addition, sterols significantly (P < 0.01) lowered absolute LDL-cholesterol concentrations after treatment but had no effect on the percentage change from the beginning to the end of the trial. Exercise significantly (P < 0.01) increased HDL-cholesterol concentrations by 7.5% and decreased triacylglycerol concentrations by 13.3% from baseline. Moreover, sterol supplementation significantly (P < 0.05) increased lathosterol, campesterol, and beta-sitosterol concentrations after treatment. Exercise significantly (P < 0.01) decreased percentage of body fat by 3.9% from the beginning to the end of the trial. CONCLUSIONS: In comparison with plant sterols or exercise alone, the combination of plant sterols and exercise yields the most beneficial alterations in lipid profiles. Implementation of such a combination therapy could improve lipid profiles in those at risk of coronary artery disease.