阿托伐他汀治疗冠状动脉粥样硬化性心脏病的疗效

目的:研究不同剂量的阿托伐他汀治疗冠状动脉粥样硬化性心脏病的疗效,并探讨性别与年龄对疗效的影响.方法:将320例冠状动脉粥样硬化性心脏病患者随机分为4组(每组80例):10mg/d阿托伐他汀治疗A组、40mg/d阿托伐他汀治疗B组、80mg/d阿托伐他汀治疗C组与常规治疗D组,其中常规治疗组采用硝酸甘油、血管紧张与素转换酶抑制剂阿司匹林等;疗程12周.分析比较各组患者治疗前后:TG、TC、HDL-C、LDL-C和hs-CRP的水平变化.结果:治疗12周后,与常规治疗组相比:①三个不同剂量的阿托伐他汀治疗组中患者的TG、TC、HDL-C、LDL-C和hs-CRP分子的浓度变化差异均有统计学意义,P＜0.05;其中以剂量为40 mg/d的阿托伐他汀治疗组的整体疗效相对最好,P＜0.05;②治疗效果与患者年龄呈负相关趋势;③在45-55岁这个年龄阶段,女性患者的治疗效果要好于同年龄阶段的男性患者,P＜0.05;④在老年患者中,大剂量的阿伐他汀的安全性明显低于中小剂量组.结论:中等剂量的阿托伐他汀对冠状动脉粥样硬化性心脏病的疗效显著,安全性良好.     

Phytoestrogens, cancer and coronary heart disease

Recent results obtained in collaboration with many other groups with regard to phytoestrogens (isoflavones and lignans) and breast cancer, prostate cancer and cardiovascular disease are presented and discussed in light of new developments in the field. Both isoflavones and lignans may be protective with regard to these diseases, but we do not yet understand some of the controversial results obtained. In this short communication the possible mechanisms of disease prevention were not discussed.     

Dietary and pharmacological antioxidants in atherosclerosis

Antioxidants that inhibit LDL oxidation are thought to be potential anti-atherogenic compounds. The results of major human randomized trials with antioxidants have, however, been disappointing, except for probucol, which consistently inhibits restenosis. Similarly, animal intervention studies show that antioxidants do not generally inhibit atherosclerosis, although some compounds provide protection. Direct evidence for the oxidation of LDL causing atherosclerosis is needed. This article summarizes results from antioxidant intervention studies, and highlights some of the key issues that need to be addressed to link biochemical changes in the arterial wall more directly to the oxidation theory of atherosclerosis.     

Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease.

The role of somatic mitochondrial DNA (mtDNA) damage in human aging and progressive diseases of oxidative phosphorylation (OXPHOS) was examined by quantitating the accumulation of mtDNA deletions in normal hearts and hearts with coronary atherosclerotic disease. In normal hearts, mtDNA deletions appeared after 40 and subsequently accumulated with age. The common 4977 nucleotide pair (np) deletion (mtDNA4977) reached a maximum of 0.007%, with the mtDNA7436 and mtDNA10,422 deletions appearing at the same time. In hearts deprived of mitochondrial substrates due to coronary artery disease, the level of the mtDNA4977 deletion was elevated 7-220-fold over age-matched controls, with the mtDNA7436 and mtDNA10,422 deletions increasing in parallel. This cumulative mtDNA damage was associated with a compensatory 3.5-fold induction of nuclear OXPHOS gene mRNA and regions of ischemic hearts subjected to the greatest work load (left ventricle) showed the greatest accumulation of mtDNA damage and OXPHOS gene induction. These observations support the hypothesis that mtDNA damage does accumulate with age and indicates that respiratory stress greatly elevates mitochondrial damage.     

Dietary flavonoids and risk of coronary heart disease

Flavonoids, a group of phenolic compounds found naturally in fruit, vegetables, nuts, flowers, seeds and bark are an integral part of the human diet. They have been reported to exhibit a wide range of biological effects, including antiischemic, antiplatelet, antineoplastic, antiinflammatory, antiallergic, antilipoperoxidant or gastroprotective actions. Furthermore, flavonoids are potent antioxidants, free radical scavengers and metal chelators, and inhibit lipid peroxidation. Oxidative modification of low-density lipoproteins (LDLs) is believed to play a crucial role in atherogenesis. Epidemiological studies have shown that the consumption of fruits and vegetables, and regular red wine consumption is related with a reduced risk of cardiovascular diseases.     

Dietary factors in the fall in coronary heart disease mortality.

The role of dietary change in the fall in heart disease mortality has been hotly debated. Three countries, Australia, USA and UK with equal 'care' and sophistication of surgical techniques have shown different timing in the beginning of the decline of this 'epidemic'; around the mid 1960s in the first two countries, but not until the late 1970s for the UK. The cause of this difference may be the changing food habits of their populations. Using food disappearance data, apparent consumption of butter and margarine show opposite trends (butter down and margarine up) predating the decline in mortality in both the USA and Australia by at least 7 years and also in the UK, but at a later time, (about 1970). Changes in adipose tissue linoleate, a marker for polyunsaturated fat intake, support this indirect evidence, with depot levels rising in the USA from the 1960s and 10 years later in the UK. Other evidence support the view of decreasing saturated fat intake and increasing polyunsaturated intake prior to 1960 in the USA. Although many factors must contribute to the decline in mortality from CHD, change in dietary P/S ratio would seem to be the major dietary contributor.     

Oxidative DNA damage,antioxidants, and cancer

Oxidised bases, such as 8-oxo-guanine, occur in cellular DNA as a result of attack by oxygen free radicals. The cancer-protective effect of vegetables and fruit is attributed to the ability of antioxidants in them to scavenge free radicals, preventing DNA damage and subsequent mutation. Antioxidant supplements (e.g., β-carotene, vitamin C) increase the resistance of lymphocytes to oxidative damage, and a negative correlation is seen between antioxidant concentrations in tissues and oxidised bases in DNA. Large-scale intervention trials with β-carotene have, however, led to increases in cancer. Recent measurements of the frequency of oxidised DNA bases indicate that earlier estimates were greatly exaggerated; there may be only a few thousand 8-oxo-guanines per cell. Convincing evidence for mutations resulting from oxidative damage, in tumours or cultured cells, is lacking. It seems that efficient antioxidant defences together with DNA repair maintain a steady-state level of damage representing minimal risk to cell or organism. BioEssays 21:238–246, 1999. © 1999 John Wiley & Sons, Inc.     

Altitude, radiation, and mortality from cancer and heart disease

The variation in background radiation levels is an important source of information for estimating human risks associated with low-level exposure to ionizing radiation. Several studies conducted in the United States, correlating mortality rates for cancer with estimated background radiation levels, found an unexpected inverse relationship. Such results have been interpreted as suggesting that low levels of ionizing radiation may actually confer some benefit. An environmental factor strongly correlated with background radiation is altitude. Since there are important physiological adaptations associated with breathing thinner air, such changes may themselves influence risk. We therefore fit models that simultaneously incorporated altitude and background radiation as predictors of mortality. The negative correlations with background radiation seen for mortality from arteriosclerotic heart disease and cancers of the lung, the intestine, and the breast disappeared or became positive once altitude was included in the models. By contrast, the significant negative correlations with altitude persisted with adjustment for radiation. Interpretation of these results is problematic, but recent evidence implicating reactive forms of oxygen in carcinogenesis and atherosclerosis may be relevant. We conclude that the cancer correlational studies carried out in the United States using vital statistics data do not in themselves demonstrate a lack of carcinogenic effect of low radiation levels, and that reduced oxygen pressure of inspired air may be protective against certain causes of death.