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Placebo controlled study on comparison of effects of Nigella sativa and nicotinic acid along with low fat diet and physical exercise on LDL-cholesterol and HDL-cholesterol

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Abstract

To get good compliance of therapeutic goal of hypolipidemic agents by cardiologist and patient, some herbal drugs have had been used by some expert cardiologists. Among those herbal medicines Kalonji is most important drug used as hypolipidemic agent. In this research work hypolipidemic effects of kalonji are compared with hypolipidemic effects of Niacin. It was single blind placebo-controlled comparative study, conducted at Jinnah Hospital, Lahore from September 2013 to December 2013. Ninety hyperlipidemic patients were enrolled after written and well explained consent. Ninety patients were divided in three groups, one group as placebo and other two groups for Niacin and kalonji. After six weeks of therapy by 2 medicines, research proved highly significant changes in LDL-cholesterol, but significant changes in HDL-cholesterol in hyperlipidemic patients.

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... With respect to clinical findings, although some randomized controlled trials (RCTs) have been performed, the reported results have been controversial [9,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]. Because of the variable duration of studies, preparation of NS employed, study designs, and recruited populations, it is difficult to draw definitive conclusions on the hypolipidemic activity of this natural supplement. ...
... The clinical trials used different forms and doses of NS. Three studies investigated NS powder 1 g/day [49,56,57], two studies investigated NS powder 1.5 g/day [47,50], one study investigated NS powder 1.6 g/day [58], three studies investigated NS powder 2 g/day [51,61,62], two studies investigated NS powder 2 spoons/day [52,60], two studies investigated NS oil 5 ml/day [48,55], one study investigated NS oil 100 mg/day [9], one study investigated NS oil 200 mg/day [9], one study investigated NS oil 1 g/day [53], and two studies investigated NS oil 3 g/day [54,59]. The range of intervention periods was from 4 weeks [52,62] up to 3 months [50,54,55,58]. ...
... The range of intervention periods was from 4 weeks [52,62] up to 3 months [50,54,55,58]. The most of included studies were parallel-group design [9,[47][48][49][50][51][52][53][54][55][56][57][59][60][61][62], only one study was cross-over design [58]. Selected trials enrolled subjects with metabolic syndrome [47,56], overweight [51], obesity [50,59], mild hypertension [9], hyperlipidemia [51,52,[60][61][62], type 2 diabetes [53][54][55], menopausal women [56][57][58], and healthy subjects [48,49] (Table 1). ...
Article
The effects of Nigella Sativa (NS) on plasma lipid concentrations are controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases were searched (up to August 2015) to identify RCTs investigating the impact of NS on total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglycerides concentrations. A random-effects model and the generic inverse variance weighting method were used for quantitative data synthesis. Meta-regression, sensitivity analysis, and publication bias assessments were performed using standard methods. A total of 17 RCTs examining the effects of NS on plasma lipid concentrations were included. Meta-analysis suggested a significant association between NS supplementation and a reduction in total cholesterol (weighed-mean-difference [WMD]: -15.65mg/dL, 95% CI: -24.67, -6.63, p=0.001), LDL-C (WMD: -14.10mg/dL, 95% CI: -19.32, -8.88, p<0.001), and triglyceride levels (WMD: -20.64mg/dL, 95% CI: -30.29, -11.00, p<0.001). No significant effect on HDL-C concentrations (WMD: 0.28mg/dL, 95% CI: -1.96, 2.53, p=0.804) was found. A greater effect of NS seed oil versus seed powder was observed on serum total cholesterol and LDL-C levels, and an increase in HDL-C levels was found only after NS seed powder supplementation. NS has a significant impact on plasma lipid concentrations, leading to lower total cholesterol, LDL-C, and TG levels while increased HDL-C is associated with NS powder only. Further RCTs are needed to explore the NS benefits on cardiovascular outcomes.
... These results agree with Gholam et al. (2019) who reported that the levels of TG, total cholesterol, LDL, ALT, and Alkaline phosphatase significantly reduced by treatment with fennel seeds extract and the level of HDL significantly increased. Previous study of Moeen-ud-din et al. (2014) showed that the intake of two teaspoons of black cumin seeds for six weeks by hyperlipidemic patients decreased their LDL-C and increased their HDL-C. Also, Mahdieh et al. (2018) reported that treatment with black cumin reduced body weight and body mass index (BMI). ...
... However, a wide range of dosages used in these studies coupled with the lack of standardization of the preparations used makes it difficult to compare these dosages with the dosages used in experimental animals in the studies discussed above. For example, clinical studies on ginseng have used a dosage of 0.5 g [266] dried roots to 6 g [267] of rootless preparation and 100 mg [266] to 800 mg [268] of a standardized extract per day; a dosage of 150 mg [269] to 5 g [270] per day has been used in studies on quercetin; a dosage of 66 mg [271] to 8 g [272] per day in studies on curcumin; a dosage of 100 mg [273] to 4 g [274] per day in studies on epigallocatechin gallate; a dosage of 1 g [275] to 10 g (2 teaspoons of Nigella sativa oil) [276] per day in studies on Nigella sativa; and a dosage of 24 mg [277] to 2.5 g [278] per day in studies on proanthocyanidins. Additionally, measures were given in form of mL or servings of the plant extract or food rich in phytochemicals in some instances. ...
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Fluorosis is a major public health problem globally. The non-availability of specific treatment and the irreversible nature of dental and skeletal lesions poses a challenge in the management of fluorosis. Oxidative stress is known to be one of the most important mechanisms of fluoride toxicity. Fluoride promotes the accumulation of reactive oxygen species by inhibiting the activity of antioxidant enzymes, resulting in the excessive production of reactive oxygen species at the cellular level which further leads to activation of cell death processes such as apoptosis. Phytochemicals that act as antioxidants have the potential to protect cells from oxidative stress. Evidence confirms that clinical symptoms of fluorosis can be mitigated to some extent or prevented by long-term intake of antioxidants and plant products. The primary purpose of this review is to examine recent findings that focus on the amelioration of fluoride-induced oxidative stress and apoptosis by natural and synthetic phytochemicals and their molecular mechanisms of action.
... The study revealed that, hyperlipidemia patients taking 2 teaspoons of N. sativa seeds for 6 consecutive weeks, showed there is a decrease in LDL-C levels and also increases HDL-C levels [39]. The study also revealed that in both male and females daily 2 spoon of N. sativa seed for 4 weeks causes increases in the HDL-C levels and reduces the body weight [40]. ...
Article
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Nigella sativa belonging to family ranunculaceae. This plant is an extensively used as medicinal plant in India as well as all over the world. Nigella sativa (N. sativa) is well known plant of traditional systems of medicine such as Ayurveda, Siddha and Unani. It is also known as nutmeg flower, black seed, black cumin, black caraway, fennel flower, roman coriander, and kalonji. Alkaloids, phenols, flavonoids, glycosides, terpenoids and steroids are the important phyto constituents of N. sativa. The active constituents of N. sativa are thymohydroquinone, p-cymene, dithymoquinone, thymoquinone, carvacrol, sesquiterpene longifolene. N. sativa seed also contains pentacyclic triterpene, alpha-hederin, protein, carbohydrates, crude fibre, fat and saponin. N. sativa oil contains oleic acid, palmitic acid, linoleic acid. Aromatics contain α-thujene, thymol, α-pinene, thymoquinone, dihydrothymoquinone. N. sativa has been used as stimulant, emmenagogue, appetizer, pungent, anthelmintic, pungent, deodorant, carminative, purgative, expectorant, febrifuge, deodorant etc. N. sativa possess numerous pharmacological action such as antibacterial, antifungal, anticancer, hepatoprotective, antioxidant, antiinflammatory, analgesic, immunomodulatory, antidiabetic, dyslipidemia, antiepileptic, gastroprotective, antioxytocic, anti-fertility, respiratory, dermatological, nephroprotective, antiviral, testicular-protective, antidepressant and anticonvulsant activity. So considering the medicinal value and its therapeutic potential this review article would spotlight on phytochemistry, chemical composition and pharmacological activity of N. sativa.
... The effects of N. sativa in comparison to nicotinic acid along with low fat diet and physical exercise in hyperlipidemia patients divided to three groups: I) placebo group, II) 2 tea spoons N. sativa after breakfast, and III) niacin 2 g in divided doses, after breakfast, lunch and dinner for the period of two months was investigated. The results showed that N. sativa and niacin significantly reduced serum level of LDL-C and increased HDL-C in hyperlipidemia patients [109] . ...
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Various pharmacological effects of Nigella sativa L. have been reported that include, antioxidant, antibacterial, antihistaminic, antihypertensive, hypoglycemic, antifungal, antiinflammatory, anticancer, and immunomodulatory. It has also been reported to produce beneficial effects in cardiovascular, gastrointestinal, reproductive and respiratory disorders. The effects of Nigella sativa had been attributed to constituents such as nigellicine, nigellidine, thymoquinone, dithymoquinone, thymol and carvacrol. In this article the cardiovascular effects of Nigella sativa and its constituents were reviewed. Published data was gathered through search engines and the findings were classified into animal and human studies. The effects of Nigella sativa and its constituents on cardiotoxicity, blood pressure, vascular smooth muscle, endothelial dysfunction, heart rate, cardiac contractility, lipid profile, platelet aggregation and atherosclerosis were reviewed. This review indicated that Nigella sativa and thymoquinone exhibited beneficial cardiovascular effects on cardiotoxicity, hypertension, hyperlipidemia, and atherosclerosis. These effects were probably due to the antioxidant and antiinflammatory properties of Nigella sativa. It seems that Nigella sativa and its constituents could be of therapeutic value in cardiovascular diseases.
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Black seeds, sometimes called black cumin, are obtained from the spicy medicinal herb Nigella sativa that is native to a broad region encompassing the eastern Mediterranean, southwest Asia, and northern Africa. The seed and its oil have a distinctive aroma and taste, diversely described as bitter, peppery, metallic, and pungent. Both are frequent ingredients in numerous foods, especially in the Middle East and India. In these same regions N sativa has an extensive history as a folk medicine dating back millenia for relief for a variety of health conditions such as asthma, headache, bronchitis, amenorrhea, allergies, infections, and hypertension. The antioxidant, anti-inflammatory, and immunomodulatory properties of N sativa seeds observed in preclinical studies provided an impetus for clinical trials examining the seeds' effects on cardiovascular, respiratory, and neurological disorders, among others. This narrative review summarizes findings from publications addressing several these and other disorders and provides suggestions for future research.
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Dyslipidemia is the major risk factor for atherosclerotic cardiovascular disease (ASCVD), cerebrovascular disease and peripheral artery disease (PAD). It is characterized by higher plasma concentrations of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c), apolipoprotein B (apoB), very low density lipoprotein-cholesterol (VLDL-c), triglycerides (TGs) and low levels of high density lipoprotein-cholesterol (HDL-c). Herbal medicines are preferred by many across the globe particularly to manage chronic conditions such as dyslipidemia, hypertension, type 2 diabetes, cancer, and plenty of others. Nigella sativa (Black seeds or Black cumin seeds) is a miracle herb employed within the management of many sicknesses for centuries. Hence, this review focuses on the ameliorative effects of N. sativa on the plasma lipid concentrations of human subjects. Numerous randomized controlled clinical trials (RCTs) and different clinical studies demonstrated that N. sativa possess potential anti-dyslipidemic activity. The patients with dyslipidemia may well be benefited by using N. sativa along with healthy lifestyle changes and statin and other antihyperlipidemic medications as adjuvant therapy if needed.
Chapter
Nigella sativa plant from Ranunculaceae family has been commonly used as traditional remedies by the ancient world such as Greeks, Romans, and Egyptians. The plant is also known black seed or black cumin. The plant is highly valued by Muslims all over the world as it has been mentioned by the Islamic Prophet Muhammad that the black seed has the capability of curing all diseases except death. The purpose of this chapter is to provide updated and categorized information on the traditional uses, chemical composition, biological activities, bioavailability, safety, toxicity, and clinical trials of N. sativa in order to explore their therapeutic potential and evaluate future research opportunities. Every part of this plant contains a valuable medicinal feature. It contains different types of active phytoconstituents like carbohydrates, volatiles, alkaloids, saponins, flavonoids, phenolics, glycoside, coumarins, fixed oils, proteins, vitamins, and minerals are present. The use of its seeds, whole plant, and oil is common for treatment of many diseases like hepatoprotective, antidiabetic, antiasthmatic, cardioprotective, analgesic, neuroprotective, antiinflammatory, antioxidant, antimicrobial, and anticancer effects. N. sativa has potential for the treatment of a wide range of diseases and has been well studied for its phytochemical properties. However, further scientific studies are needed to explore mechanisms of actions, adverse effects of the extracts, the effective therapeutic dose, and the therapeutic effect of major secondary metabolites.
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The aim of this systematic review and meta‐analysis was to evaluate the effects of Nigella sativa (N. sativa) on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress. Two independent authors systematically examined online databases consisting of, EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until October 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of the studied trials. The heterogeneity among the included studies were assessed using the Cochrane's Q test and I‐square (I²) statistic. Data were pooled using a random‐effects model and weighted mean difference (WMD) was considered as the overall effect size. A total of 50 trials were included in this meta‐analysis. We found a significant reduction in total cholesterol (WMD: −16.80; 95% CI: −21.04, −12.55), triglycerides (WMD: −15.73; 95% CI: −20.77, −10.69), LDL‐cholesterol (WMD: −18.45; 95% CI: −22.44, −14.94) and VLDL‐cholesterol (WMD: −3.72; 95% CI: −7.27, −0.18) following supplementation with N. sativa. In addition, there was significant reductive effect observed with N. sativa on fasting glucose (WMD: −15.18; 95% CI: −19.82, −10.55) and HbA1C levels (WMD: −0.45; 95% CI: −0.66, −0.23). Effects of N. sativa on CRP (WMD: −3.61; 95% CI: −9.23, 2.01), TNF‐α (WMD: −1.18; 95% CI: −3.23, 0.86), TAC (WMD: 0.31; 95% CI: 0.00, 0.63), and MDA levels (WMD: −0.95; 95% CI: −2.18, 0.27) were insignificant. This meta‐analysis demonstrated the beneficial effects of N. sativa on fasting glucose, HbA1c, triglycerides, total‐, VLDL‐, LDL‐cholesterol levels.
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Objectives Nigella sativa (black seed or black cumin), which belongs to the Ranunculacea family, is an annual herb with many pharmacological properties. Among its many active constituents, thymoquinone (TQ) is the most abundant constituent of the volatile oil of Nigella sativa (N. sativa) seeds, and it is the constituent to which most properties of this herb are attributed. Methods PubMed-Medline, Scopus, and Web of Science databases were searched to identify randomized control trials (RCTs) investigating the therapeutic effects of N. sativa and/or TQ. In this review, we investigated the clinical uses of N. sativa and TQ in the prevention and the treatment of different diseases and morbidity conditions in humans. Results Black seed and TQ are shown to possess multiple useful effects for the treatment of patients with several diseases, such as inflammatory and auto-immune disorders, as well as metabolic syndrome. Also, other advantages, including antimicrobial, anti-nociceptive and anti-epileptic properties, have been documented. The side effects of this herbal medicine appear not to be serious, so it can be applied in clinical trials because of its many advantages. Conclusion Some effects of N. sativa, such as its hypoglycemic, hypolipidemic and bronchodilatory effects, have been sufficiently studied and are sufficiently understood to allow for the next phase of clinical trials or drug developments. However, most of its other effects and applications require further clinical and animal studies.
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The atherogenic pattern of dyslipidemia associated with type 2 diabetes mellitus (DM) has been increasingly discussed. We have recently reported a hypoglycemic effect of Nigella sativa (NS) seeds in patients with type 2 DM. In this study we sought to assess the impact of NS seeds on lipid profile in type 2 diabetic patients. A total of 94 patients with type 2 DM were recruited and divided into 3 dose groups. Capsules containing NS were administered orally in a dose of 1, 2, and 3 g/day for 12 weeks. All patients were subjected to measurement of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) before treatment and 4, 8, and 12 weeks thereafter. Patients receiving 1 g/day NS seeds for 12 weeks (group 1) showed nonsignificant changes in all the parameters except for a significant increase in HDL-c after 4 weeks of treatment. However, patients ingested 2 g/day NS displayed a significant decline in TC, TG, and LDL-c, and a significant elevation in HDL-c/LDL-c, compared with their baseline data and to group 1 patients. Increasing NS dose to 3 g/day failed to show any increase in the hypolipdemic effect produced by the 2 g/day dose. NS supplementation at a dose of 2 g/day for 12 weeks may improve the dyslipidemia associated with type 2 diabetic patients. Therefore, NS is a potential protective natural agent against atherosclerosis and cardiovascular complications in these patients.
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Although low-density lipoprotein cholesterol (LDL-C) lowering represents the mainstay of current lipid treatment, high-density lipoprotein cholesterol (HDL-C) has generated increasing interest as a secondary therapeutic target because of strong evidence that serum HDL-C concentration is inversely associated with coronary heart disease risk. Niacin is a lipid-altering drug that has been used to lower cholesterol since the 1950s. In addition to its LDL-C-lowering effects, niacin is the most effective agent currently available for raising HDL-C. Despite its long history as a lipid-altering drug, only limited data are available regarding its clinical benefit alone and in combination with other agents, and the majority of studies investigating its impact on clinical outcomes are from the pre-statin area. Several studies have demonstrated a beneficial effect of treatment with niacin in combination with statin therapy on surrogate cardiovascular markers (e.g. carotid intima-media thickness). However, the clinical significance of these surrogate markers has been questioned. Two large randomized trials will address whether niacin-statin combination therapy is an appropriate therapeutic alternative to statin monotherapy.
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We have studied the effect of thymoquinone on the blood levels of cholesterol, triglycerides, HDL and LDL in albino rats. A total of 200 rats, 150 test group and 50 as controls, were included in the study. Six doses of thymoquinone (0.5, 1, 2, 4, 6, and 8 mg/kg/day) were given through intraperitonial injections at 8 Am. The drug was administered for 5 durations 1, 4, 7, 10, and 14 days. Thymoquinone produced significant reduction in the blood level of all parameters studied. There was no linear dose or time dependent effect on these parameters. The effect of thymoquinone started after 4 days with all doses and continued, with some swings, in the rest of the duration. The dose of 8 mg/kg was found to be toxic. It is concluded that thymoquinone has a hypocholestrolemic as well as a reducing effect on triglycrides, HDL and LDL. Therefore, we recommend further research on the therapeutic effect of thymoquinone in related diseases in humans and animals.
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The effect of 2 weeks daily treatment with 2 g Nigella sativa (N. sativa) on the blood levels of glucose, uric acid, cholesterol, triglycerides, BUN and creatinine was studied on 16 second year male medical students. Nine students took 2 capsules of 500 mg N. sativa twice daily and served as the test group. Seven students served as controls and took 2 capsules of 500 mg brown sugar twice daily. In the test group, the parameters which showed a significant decrease by the end of the first week of treatment were glucose (p < 0.01) and cholesterol (p = 0.05). However, both levels went up by the end of the second week of the treatment but remained below baseline. Creatinine was significantly elevated (p < 0.01) by the end of the first week. Uric acid showed a progressive but a nonsignificant decrease. A finding of interest was that the control group showed a progressive and significant increase in uric acid. It is concluded that N. sativa has a potential reducing effect on the blood levels of both glucose and cholesterol.
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The Nigella sativa L. seed oil (petroleum ether extracted) was found to be present to the extent of 33–33.8 % in the seeds. Steam distillation removed a 1.4 % of a volatile oil and left a fatty oil. The physical and chemical constants of the oil were determined and are shown in Table I. The saturated fatty acids were found to constitute 11.8 % of the whole fatty acid fraction and consisted of myristic, palmitic and stearic acids. The spectrophotometric determination of the unsaturated fatty acids showed the presence of oleic 48.76 %, linoleic 37.56 % and linolenic acid 1.88 %. β–Sitosterol was isolated from the nonsaponifiable matter. It was identified through direct comparison of the free alcohol, its acetate and benzoate with authentic material. Also the 3,5–dinitrobenzoate was prepared. Furthermore the identity was proved using thin–layer chromatography. Die Samen von Nigella sativa enthalten 33,0–33,8 % ol (Petrolather–Extrakt). Durch Dampfdestillation wurden 1,4 % atherisches ol vom fetten ol abgetrennt. Die physikalischen und chemischen Konstanten des Ols wurden bestimmt. Der Anteil an gesattigten Fettsauren betrug 11,8 % und bestand aus Myristin–, Palmitin– und Stearinsaure. Auf spektrographischem Wege liesen sich an ungesattigten Fettsauren 48,76 % Oleinsaure, 37,56 % Linolsaure und 1,88 % Linolensaure nachweisen. Aus dem nicht verseifbaren Anteil konnte β–Sitosterol isoliert und identifiziert werden.
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To minimize the cutaneous flushing symptoms associated with niacin use, a time-release capsule form of niacin has been formulated. Thus study compares the effects of time-release niacin with those of unmodified niacin on lipoprotein lipids, including HDL2 and HDL3, apoproteins A-I and A-II, clinical chemistries, symptomatic side effects, and adherence to the medication regimen. Seventy-one primarily hypercholesterolemic subjects were randomized to either unmodified niacin or time-release niacin ad took medication for a six-month period. The two groups were closely matched on anthropomorphic and lipid variables. Adherence to the therapeutic regimen at a dose of 1.5 g/d in the first month of treatment was similar in the two groups. Thereafter, at a dose of 3.0 g/d, adherence was in excess of 90% among subjects taking unmodified niacin but only 64% among those taking time-release niacin, chiefly because of aggravated gastrointestinal symptoms; cutaneous flushing side effects, however, were slightly less common with time-release niacin. At these levels of adherence, LDL cholesterol (C) was reduced 21% by unmodified niacin and 13% by the time release form. Plasma total triglyceride was reduced more with unmodified niacin (27%) than with time-release niacin (8% maximum), and HDL-C and HDL2-C were increased significantly with unmodified niacin (26% and 36%) and were not significantly changed by time-release niacin. Increased to a similar degree on both regimens were HDL3-C (approximately 35%) and apoA-I (approximately 12%). ApoA-II was not affected by either drug regimen.(ABSTRACT TRUNCATED AT 250 WORDS)
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Treatment with statins markedly reduces levels of LDL-cholesterol, and large, well-designed evaluations of these agents have demonstrated reductions in cardiovascular event rates of ∼20–40&percnt;. Additional therapeutic strategies will be required to make further inroads into the substantial residual burden of cardiovascular disease in statin-treated patients. Epidemiological studies over several decades and outcome studies with agents that raise levels of this lipoprotein (nicotinic acid or fibrates) have established low HDL-cholesterol as an important therapeutic target. Combining agents which decrease LDL-cholesterol and increase HDL-cholesterol within a single regimen might provide a means of improving cardiovascular prognosis beyond that possible with statins alone. Six randomized clinical trials involving treatment with nicotinic acid in combination with a statins or bile acid sequestrant have demonstrated regression, or markedly slowed progression, of atherosclerosis in patients at high risk of a cardiovascular event. Three of these trials, the HDL-Atherosclerosis Treatment Study, the Familial Atherosclerosis Treatment Study, and the Armed Forces Regression Study, have associated these benefits with significant improvements in clinical outcomes. Correcting low HDL-cholesterol in statin-treated patients may provide a means to achieve the next leap forward in the management of cardiovascular disease.
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This preliminary report describes the simplest and possibly earliest lipid-containing lesions induced in aortas of rabbits fed a cholesterol-containing diet. Subendothelial accumulation of unesterified cholesterol, detected with filipin dye, appears to precede morphologic changes in endothelium and accumulation of subendothelial lipid-containing "foam" cells. The origin of subendothelial unesterified cholesterol remains to be determined.
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Low-density lipoproteins (LDLs) carry most of the cholesterol in human plasma, and high levels of LDL cholesterol clearly cause heart disease. In recent years, many scientists have focused on elucidating the pathophysiologic steps that lie between elevated levels of LDL in the plasma and atherosclerotic plaques in the arterial wall. A large number of scientific studies indicate that oxidation of LDL within the arterial wall may be an important early step in atherogenesis. The uptake of oxidized LDL by macrophages is a likely explanation for the formation of macrophage foam cells in early atherosclerotic lesions. In addition, oxidized LDL has many other potentially proatherogenic properties.
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To study the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitor atorvastatin on the potential mechanisms involved in the recruitment of monocytic cells into the vessel wall. Inhibitors of HMG-CoA-reductase reduce cardiovascular mortality though the mechanisms yet elucidated. Most ischemic events are secondary to disruption of atherosclerotic plaques highly infiltrated by macrophages. Atherosclerosis was induced in the femoral arteries of rabbits by endothelial damage and atherogenic diet for 4 weeks. Then, animals were switched to standard chow and randomized to receive either no treatment or atorvastatin (5 mg/kg/d) and killed after 4 weeks. Atorvastatin induced a significant reduction in serum lipids and in lesion size. Arterial macrophage infiltration was abolished by the treatment, and monocyte chemoattractant protein-1 (MCP-1) was significantly diminished in the neointima and in the media. Nuclear factor kappa-B (NF-kappaB) was activated in the 60% of the lesions, both in macrophages and vascular smooth muscle cells (VSMC), of the untreated group while only in 30% of the atorvastatin group. NF-kappaB activity was also lower in the uninjured aorta and liver of treated compared with untreated rabbits. In cultured VSMC, MCP-1 expression and NF-kappaB activity induced by tumor necrosis factor alpha were downregulated by atorvastatin. In a rabbit atherosclerosis model, atorvastatin diminishes the neointimal inflammation, and this could contribute to the stabilization of the atherosclerotic plaque. This may be an additional explanation for the reduction of acute ischemic events in patients treated with statins.
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Low HDL-cholesterol is a strong independent cardiovascular risk factor recognized as a therapeutic target in recent guidelines. The Pan-European Survey on HDL-cholesterol collected data on plasma lipid profiles from 8545 dyslipidaemic patients in the care of 1339 specialist physicians in 11 European countries. The main objective was to obtain a reliable estimation of the prevalence of low HDL (< 1.03 mmol/L [< 40 mg/dL] in men; < 1.29 mmol/L [< 50 mg/dL] in women). Eligible patients were aged >or= 18 years and had received diet and exercise plus pharmacologic lipid-modifying treatment for >or= 3 months, or had serum cholesterol >or= 5.18 mmol/L (>or= 200 mg/dL) and/or serum triglycerides >or= 2.03 mmol/L (>or= 180 mg/dL) despite >or= 3 months of diet and exercise. The survey population was overweight (mean body mass index 29.0 kg/m2), with a high prevalence of sedentary lifestyle (68%), type 2 diabetes (45%), hypertension (72%) and coronary heart disease (45%). Lipid-modifying treatment, received by 85% of patients, included lifestyle modification (85%) and/or lipid-lowering drugs (85% received a statin). The prevalence of low HDL-cholesterol despite lipid-modifying treatment was 40% (women) and 33% (men). Very low HDL-cholesterol (< 0.90 mmol/L [< 35 mg/dL]) occurred in 14% of treated patients, with similar prevalence in the subgroup of patients not receiving such treatment. Hypertriglyceridaemia (> 1.69 mmol/L [> 150 mg/dL]) occurred in 57% of men not under lipid-modifying treatment and in 47% of men receiving such treatment; corresponding values in women were 48% and 43%. Both low HDL-cholesterol and hypertriglyceridaemia occurred in 26% of men and 27% of women who were not receiving lipid-modifying treatment and in 21% of men and 25% of women receiving lipid-modifying treatment. Low HDL-cholesterol and hypertriglyceridaemia are, therefore, common among European patients treated for dyslipidaemia. Clearly, physicians need to focus more of their attention on this major risk factor and to consider adequate treatment when indicated.