P-选择素与缺血性脑血管病

P-选择素又称CD62,通过介导内皮细胞和血小板的活化以及动脉粥样硬化的形成和发展等过程,促进缺血性脑血管病的发生.多项研究证实,P-选择素在缺血性脑血管病危险因素,如高血压、糖尿病、高胆固醇血症、心脏病、吸烟、酗酒、高纤维蛋白原血症等的发生和发展中起重要作用.P-选择素能否作为独立危险因素预测缺血性脑血管病的发生,尚待进一步研究证实.     

Anti-cytomegalovirus antibodies and other atherosclerosis risk factors in patients with cardiovascular diseases

Objective To determine anti-cytomegalovirus (CMV) antibodies along with anti-Chlamydia pneumoniae (CP)antibodies in comparison with inflammatory markers and other risk factors of atherosclerosis in patients with selected cardiovascular diseases(CVD).Methods A total of 228 patients with coronary heart disease (CHD) and/or hypertension (HT), and those who underwent reconstructive vascular surgery (RVS) on carotids or abdominal aorta were tested for the presence of anti-CMV IgG and IgM antibodies as well as for anti-CP IgA antibodies, C-reactive protein (CRP),and interleukin-6 (IL-6). Other risk factors for atherosclerosis, namely age, gender,smoking, hypercholesterolemia, and diabetes mellitus were also analyzed. Results Anti-CMV IgG antibodies were found in 204 patients sera (89.5%),compared with 46 positive of 68 sera in the controls (67.6%), whereas anti-CMV IgM antibodies were detected in 4 of 54 sera of patients tested (7.4%), but not in the controls. The highest proportion of positive sera with not only anti-CMV IgG antibodies (95.6.7%),but also anti-CP IgA antibodies (78.3%), IL-6 (84.8%) and CRP (97.8%), was observed in patients with RVS. The results obtained corresponded to age, hypercholesterolemia, and diabetes. Conclusions The presence of anti-CMV antibodies together with antibodies to CP and markers of inflammation (CRP and IL-6) in our study was associated with CVD, primarily in elderly patients who underwent RVS.     

The risk factors for ischemic heart disease in young adults

We reviewed the histories and laboratory data of 67 young patients with ischemic heart disease under the age of 40 years. Twenty-three cases were associated with hypercholesterolemia. Of these, 10 were of the familial type. Twenty patients had hypertension, while 14 were diabetics and 13 were heavy smokers. It is noteworthy that 13 of 17 patients with multi-vessel disease and hypercholesterolemia. Significant atherosclerotic coronary stenosis was demonstrated in 51 cases. The incidences of hypercholesterolemia, hypertension and diabetes mellitus in these 51 patients were not only significantly higher than those in age-matched normal health subjects and young patients with non-ischemic heart disease, but also higher than those in patients with ischemic heart disease over the age of 40 years. The results indicated that hypercholesterolemia is the most important risk factor for ischemic heart disease in young patients, although the three previously accepted risk factors (hypertension, diabetes mellitus and cigarette smoking) were all associated with the development of the disease. We could not find any obvious risk factor in 18 young patients with ischemic heart disease, including 12 cases of myocardial infarction. Myocardial infarction in the absence of any obvious risk factor occurred during strenuous physical exercise in 5 patients and following excessive alcohol consumption in 4.     

Immunoglobulin-bound lipoproteins (Ig-Lp) as markers of familial hypercholesterolemia, xanthomatosis and atherosclerosis

In autoimmune hyper- or dislipidemia secondary to a monoclonal antilipoprotein gammapathy, immunoglobulin-lipoprotein (Ig-Lp) complexes are found in the circulating blood. In order to determine their possible significance in common types of hyperlipidemia we compared the Ig-Lp content of sera from 98 healthy blood donors and 155 outpatients from a Lipid Clinic, including 91 cases of hypercholesterolemia (55 familial and 36 non-familial), 15 cases of hypertriglyceridemia, 20 cases of mixed hyperlipidemia and 29 miscellaneous cases. Detection of the Ig-Lp was performed by an ELISA technique with polyclonal affinity purified anti-LDL + HDL as capture antibodies and peroxidase-labeled anti-Ig antibodies specific for IgA, IgG, IgM heavy chains as indicators. Two cases of monoclonal gammapathy (one IgA K and one IgG L) with dislipidemia served as positive controls for the test. IgG, IgA and IgM Lp were found in the sera of the blood donors, in very small quantities when compared with the monoclonal gammapathy cases. All three types of Ig-Lp were also found in the different hyperlipidemic populations studied. When blood donors were compared to hyperlipidemic patients, no difference was observed for IgG Lp. A significant increase in IgM Lp was found in patients with familial hypercholesterolemia (P less than 0.01). An increase in IgA Lp was also found in hypercholesterolemia, familial or not (P less than 0.01), and in patients with corneal arcus (P less than 0.0001), ischaemic disease (P less than 0.01), tendon xanthomas (P less than 0.05) or xanthelasma (P less than 0.05). Furthermore, in a group of 18 paired parents from 9 different families, positive interparent correlations were found for IgM Lp (r = 0.78; P = 0.013) and IgG Lp (r = 0.69; P = 0.038). Therefore IgM Lp may be markers for subpopulations of familial hypercholesterolemia, and IgA Lp markers for the risk of atherosclerotic ischemic disease and deposition of lipids in the cornea. It may be (1) that natural clones of autoanti-lipoprotein antibodies are responsible for the minute quantities of Ig-Lp found in normal people; (2) that the marked development of one of these clones is the cause of autoimmune hyper- or dyslipidemia and xanthomatosis associated with monoclonal gammapathy; (3) that the limited development of a clone produces the Ig-Lp particles found in hypercholesterolemic patients; (4) that there are types of Ig-Lp particles (IgA Lp) that may be harmful for tissues independently of hypercholesterolemia.     

Influence of resting heart rate on mortality in patients undergoing coronary angiography (from the Ludwigshafen Risk and Cardiovascular Health [LURIC] study)

Atherosclerosis is the main cause of cardiovascular disease, but the extent of atherosclerosis in individual patients is difficult to estimate. A biomarker of the atherosclerotic burden would be very valuable. The aim of the present study was to evaluate the association of plasma osteoprotegerin (OPG) to clinical and subclinical atherosclerotic disease in a large community-based, cross-sectional population study. In the Copenhagen City Heart Study, OPG concentrations were measured in 5,863 men and women. A total of 494 participants had been hospitalized for ischemic heart disease or ischemic stroke, and compared to controls, this group with clinical atherosclerosis had higher mean OPG (1,773 vs 1,337 ng/L, p <0.001) and high-sensitivity C-reactive protein (2.3 vs 1.6 mg/L, p <0.001). In a multivariate model with age, gender, body mass index, hypertension, diabetes, hypercholesterolemia, smoking status, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and OPG, OPG remained significantly associated with clinical atherosclerosis (p <0.01); high-sensitivity C-reactive protein, in contrast, did not (p = 0.74). In the control group without clinical atherosclerosis, OPG was independently associated with hypertension, diabetes, hypercholesterolemia, smoking, and subclinical peripheral atherosclerosis as measured by ankle brachial index. For each doubling of the plasma OPG concentration, the risk for subclinical peripheral atherosclerosis increased by 50% (p <0.001) after multivariate adjustment. In conclusion, OPG appears to be a promising biomarker of atherosclerosis that is independently associated with traditional risk factors of atherosclerosis, subclinical peripheral atherosclerosis, and clinical atherosclerotic disease such as ischemic heart disease and ischemic stroke.     

The role of smoking in abdominal aortic aneurysm development

Abdominal aortic aneurysm is common. The aim of this study was to assess the effect of smoking on prevalence and management. Patients attending the vascular unit and appropriate controls were prospectively recruited. A smoking history revealed tobacco exposure in pack years. Serum cotinine was assessed biochemically. Independent risk factors were statistically determined. In all, 202 (186 men) patients were recruited, with 202 (197 men) controls. A total of 69 patients tested positive for cotinine, whereas 39 controls were positive (P = .001). Smoking and ischemic heart disease were significant predictors for aneurysm prevalence. Cardiac disease emerged as a more important predictor than smoking in symptomatic patients. In noncardiac patients, smoking and hypercholesterolemia were significant risk factors. Smoking is a significant predictor for aneurysm development. In high-risk patients, the cardiac disease process is the most important factor, with control of this imperative. However, in noncardiac patients, smoking cessation and lipid-lowering therapy are crucial.     

Joint effects of Chlamydia pneumoniae infection and classic coronary risk factors on risk of acute myocardial infarction

Background

Although not in itself strongly predictive of coronary heart disease, Chlamydia pneumoniae infection could interact with classic risk factors in determining risk of acute myocardial infarction (AMI).

Methods

We assessed C pneumoniae immunoglobulin (Ig) G and IgA titers and classic risk factors in 618 patients with AMI and in 967 controls.

Results

IgG titers were not related to AMI, but a significant association was seen between IgA titers and AMI. Excess risk of AMI was noted mainly among patients with the highest IgA titers, such as those beyond 2.88 (the 95th percentile cutoff point in control subjects), showing a 1.8-fold increase in risk (odds ratio 1.75, 95% CI 1.04-2.92). Classic risk factors did not differ between subjects with IgA titers above and below the 95th percentile cutoff. However, in multivariate analyses, models incorporating both IgA titers and a classic risk factor such as obesity, hypercholesterolemia, or smoking predicted risk more effectively than single-parameter models. For example, the odds ratio for AMI among subjects with the highest IgA titers plus hypercholesterolemia was greater than the product of individual risks associated with these high IgA titers and with hypercholesterolemia.

Conclusions

Interactions with classic risk factors (ie, obesity, hypercholesterolemia, and smoking), increased the predictive value of C pneumoniae IgA antibody titers in determining risk of AMI.     

Autoantibodies to the atheroma component beta2-glycoprotein I and risk of symptomatic peripheral artery disease

Peripheral artery disease (PAD) is mostly related to atherosclerosis. Autoimmunity and, in particular, antibodies to cardiolipin (aCL) and phospholipid cofactors such as beta2-glycoprotein I (beta2-gpI) might influence the development of atheroma. Beta2-glycoprotein I (beta2-gpI) has been found in atheroma. It has previously been shown that immunoglobulin A (IgA) anti-beta2-gpI antibodies are associated with a risk of cerebral ischemia and myocardial infarction. This case control study aimed to determine whether elevated levels of aCL/anti-beta2-gpI antibodies are associated with a risk of symptomatic PAD (sPAD). Cases comprised a nonselected population of patients with sPAD (intermittent claudication or critical ischemia). Patient recruitment was based on arteriography changes. Controls were selected from patients admitted to orthopedic wards as a result of fractures or muscle-ligamentous disorders. Age, sex, race, hypertension, smoking, diabetes mellitus, and hypercholesterolemia were evaluated as risk factors in both groups. IgG/IgM/IgA aCL and anti-beta2-gpI were detected by enzyme-linked immunoabsorbant assays (ELISA). To estimate the grade of association of antibodies with sPAD, odds ratios (OR) were calculated. Logistic regression was utilized for adjustment of confounding factors. Seventy-seven cases and 93 controls were studied. The mean age was 61.5 years for cases and 47.5 years for controls (p <0.001). Among the risk factors evaluated, the presence of hypertension showed the strongest association with sPAD (OR 12.1; 95%CI 5.8-30). The presence of IgA anti-beta2-gpI was independently associated with sPAD (OR 5.4; 95%CI 1.8-15.8; p = 0.01). IgA aCL was strongly associated with the outcome (nonadjusted OR 11.5 after Agresti correction). IgA aCL and IgA anti-beta2-gpI antibodies were not associated with any known risk factors for sPAD or with arteriography changes. The occurrence of these autoantibodies might represent one of the links between autoimmunity and atherosclerosis in patients with sPAD.     

Hyperinsulinemia, lipoprotein (a), and Chlamydia pneumoniae antibodies--are they risk factors or serologic predictors for progression of coronary artery disease?

The authors studied 134 patients with unstable angina pectoris symptoms and 32 subjects without coronary artery disease (CAD) for the presence of classical risk factors such as hypercholesterolemia, smoking, and family history of CAD. In addition they analyzed plasma insulin levels, lipoprotein (a) (Lp [a]) levels, and antibody titers against Chlamydia pneumoniae. All patients had a heart catheterization. Patients with diabetes mellitus were excluded from the study. Fasting insulin, low-density lipoprotein (LDL) cholesterol and Chlamydia pneumoniae immunoglobulin G (IgG) and IgA antibody titers did not show any difference in CAD from healthy control subjects, whereas Lp(a) was increased and high-density lipoprotein (HDL) decreased in CAD patients. These data indicate that lipoprotein (a), low HDL cholesterol, and smoking, but neither hyperinsulinemia nor elevated Chlamydia pneumoniae titers, are risk factors or predictors for CAD.     

Chlamydial LPS antibodies,intima-media thickness and ischemic events in patients with established atherosclerosis

BACKGROUND: Chlamydia pneumoniae has been associated with cardiovascular disease. However, studies on the presence of chlamydial antibodies and intima-media thickness (IMT) or future ischemic events are inconclusive. We examined the relation between circulating antibodies to chlamydial lipopolysaccharide (cLPS Ab), IMT and the occurrence of ischemic events during follow-up in patients with manifest atherosclerotic disease. METHODS: IgG and IgA antibodies against cLPS were determined in 273 out of 307 consecutive patients with a recent ischemic stroke (IS, n=90), a recent myocardial infarction (MI, n=87) or peripheral arterial disease (PAD, n=96). B-mode ultrasound IMT measurement of carotid and femoral arteries was performed and ischemic events, IS or MI, during follow-up were registered. RESULTS: IgG and IgA were found in 66 and 46% of the patients, respectively. We did not detect any difference in IMT between patients with or without antibodies: IgA-0.97(0.28) mm versus IgA+0.95(0.26) mm, P=0.63, IgG-0.96(0.28) mm versus IgG+0.96(0.26) mm, P=0.98. During follow-up with a mean duration of 3.5 years the combined endpoint, MI or IS, was similar in patients with or without antibodies (IgA-24% vs. IgA+19%, IgG-23% vs. IgG+22%). However, a lower frequency of MI was observed in IgA positive patients (IgA-13% vs. IgA+8%). The number of ischemic events in the 12 patients who used anti-chlamydial antibiotics was similar compared with those who did not use antibiotics. CONCLUSION: In patients with manifest atherosclerotic disease no association between the presence of cLPS Ab and IMT could be detected. In addition, no influence of cLPS Ab on the number of ischemic events was observed, the frequency of MI during follow-up in IgA positive patients was even lower.     

Synergistic Effects of Risk Factors

Risk factors for coronary heart disease (CHD), stroke, congestive heart failure and total mortality were analysed in two random population samples of men in Gothenburg, Sweden, aged 50 and 47—55 years, respectively, at entry.

A series of potential risk factors for the above mentioned end-ponsts have been analysed in univariate and multivariate logistic analyses. Population attributable risks were also calculated.

Significant risk factors in multivariate analyses are summarized. For CHD they were: family history of CHD, hypercholesterolemia, hypertension, tobacco smoking, psychologic stress, low social class and diabetes mellitus. In hypertensives, proteinuria was measured and found to be significant also.

Stroke risk factors were: family history of stroke, blood pressure, smoking, high waist/hip ratio, high plasma fibrinogen, psychologic stress, proteinuria, atrial fibrillation and transitory ischemic attacks.

Hypertension, smoking, high waist/hip ratio and psychologic stress were risk factors for congestive heart failure.     

Haplotype of the angiotensinogen gene is associated with coronary heart disease in familial hypercholesterolemia

OBJECTIVE: Familial hypercholesterolemia is characterized by high plasma low-density lipoprotein cholesterol levels and premature coronary heart disease. Despite the monogenetic origin of familial hypercholesterolemia, the incidence of coronary heart disease varies considerably among patients, which is only partly explained by classical risk factors. Hypertension is an important risk factor for coronary heart disease that is associated with angiotensinogen levels. Therefore, we analyzed the angiotensinogen gene as a modifier gene for coronary heart disease risk in patients with familial hypercholesterolemia. METHODS: In a cohort of 1785 familial hypercholesterolemia patients, we reconstructed five frequent haplotypes of the angiotensinogen gene, based on four polymorphisms. The five haplotypes cover approximately 98% of the genetic diversity accounted for by these four polymorphisms. The associations between the haplotypes and coronary heart disease were analyzed with the haplo.stats program, adjusted for age, sex and smoking. RESULTS: Patients homozygous for the C allele of the 4072 T>C polymorphism had a 34% increased coronary heart disease risk (P = 0.017) compared to patients homozygous for the T allele. Haplotype H3, consisting of the minor allele of the 4072T>C polymorphism and the major alleles of the other polymorphisms, had a frequency of 15% and was associated with a 45% increased coronary heart disease risk (P = 0.006) compared to the wild-type haplotype H1. CONCLUSIONS: We conclude that genetic variation in the angiotensinogen gene contributes to coronary heart disease risk in patients with familial hypercholesterolemia.     

Cardiovascular disease epidemiology and risk factors in primary care

INTRODUCTION AND OBJECTIVES: To study the prevalence of and risk factors for cardiovascular disease in primary care. PATIENTS AND METHOD: A cross-sectional study was carried out at an urban health center in Barcelona, Spain. In total, 2248 patients > or =15 years old were selected randomly from medical records. The study investigated cardiovascular diseases such as ischemic heart disease, cerebrovascular disease and peripheral arterial disease, and cardiovascular risk factors such as age, sex, smoking, high blood pressure, hypercholesterolemia, hypertriglyceridemia, and diabetes mellitus. RESULTS: The patients' mean age was 49.1 (18.9) years and 53.5% were male. Cardiovascular risk factor prevalences were: smoking, 35.2%; high blood pressure, 33.7%; hypercholesterolemia, 21.9%; hypertriglyceridemia,12.7%; and diabetes mellitus, 15.8%. Overall, 57.9% of patients had at least 1 cardiovascular risk factor. Significantly more males presented with each risk factor (P<.05), apart from high blood pressure. The prevalence of all risk factors, except smoking, increased with age until 74 years and then stabilized, except high blood pressure, which continued to increase. Around 10% had cardiovascular disease, with myocardial ischemia in 5.5%, cerebrovascular disease in 3.7%, and peripheral arterial disease in 2.4%. All except cerebrovascular disease were significantly more common in males (P<.05). The prevalence of cardiovascular disease was low in individuals <55 years old, particularly women, and increased with age for all forms of disease. Some 68.3% were > or =65 years old. CONCLUSIONS: The high prevalence of cardiovascular risk factors was confirmed. Cardiovascular disease was more common in males and the elderly.     

Plasma high-density lipoproteins and ischemic heart disease: studies in a large kindred with familial hypercholesterolemia.

The expression of ischemic heart disease was studied in a large kindred with familial hypercholesterolemia. Tendon xanthomas, multiple generation transmission, and the appearance of bimodality in the distributions of total and low-density lipoprotein cholesterol were found. The segregation ratio was 0.9 in females and 0.43 in males, a difference first apparent during adolescence. The upper quartile of total and low-density lipoprotein cholesterol contained all but two cases of ischemic disease, whereas the lower quartile of high-density lipoprotein cholesterol contained one half of the cases. The ratio of high- to low-density lipoprotein cholesterol (range, 0.06 to 1.6) was less than or equal to 0.20 in each patient with ischemic disease. The association of a low level of high-density lipoprotein cholesterol with ischemic disease persisted after adjustment for differences in other lipids and lipoproteins. A low level of high-density lipoprotein cholesterol, as well as a high level of low-density lipoprotein cholesterol, may influence the development of ischemic heart disease in this disorder.     

冠心病患者HCMV抗体和HCMV-DNA的测定及其临床意义

目的　探讨人巨细胞病毒 (HCMV)感染与冠心病的关系及 HCMV感染可否作为冠心病的独立危险因子。方法　间接酶联免疫吸附试验 (ELISA)测定 HCMV- Ig G、HCMV- Ig M和 HCMV- Ig A抗体 ,聚合酶链反应 (PCR)测定 HCMV- DNA。结果　冠心病组的 HCMV- Ig G、Ig M、Ig A抗体阳性率、S/N值 (标本 450 nm吸光度值 /阴性对照 450 nm吸光度值 )和 HCMV- DNA阳性率均明显高于对照组 ,且这些指标不受血清胆固醇、甘油三酯水平及是否伴有高血压和 /或糖尿病的影响 (除 HCMV- Ig M抗体阳性率在是否伴有高血压和 /或糖尿病两组间比较 P<0 .0 5外 ,余均为 P>0 .0 5)。结论　 HCMV感染可能与冠心病有关 ,HCMV感染有可能作为冠心病的独立危险因子。     

Association between anti–cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis

Objective

Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease that may not always be related to the presence of traditional cardiovascular risk factors. The aim of this study was to determine if anti–cyclic citrullinated peptide (anti‐CCP) antibodies are associated with cardiovascular disease in patients with RA.

Methods

Anti‐CCP antibodies were determined by enzyme‐linked immunosorbent assay in the earliest serum sample available from 937 patients with a diagnosis of RA. We studied the relationship between anti‐CCP antibodies with traditional cardiovascular risk factors and cardiovascular events.

Results

We found positive anti‐CCP antibodies (>25 units/ml) in 672 patients (71.7%). There was no association between the anti‐CCP antibodies and cardiovascular risk factors such as smoking, hypertension, dyslipidemia, being overweight, or diabetes mellitus. However, patients who had positive anti‐CCP antibodies experienced more frequent ischemic heart disease (6.5% versus 2.6%; odds ratio [OR] 2.58, 95% confidence interval [95% CI] 1.17–5.65) and had higher mortality rates (11.2% versus 6.8%; OR 1.72, 95% CI 1.01–2.91). Similar results were obtained when we considered anti‐CCP titers 20‐fold higher (>500 units/ml). Multivariable analysis showed that ischemic heart disease is independently associated with positive anti‐CCP antibodies (OR 2.8, 95% CI 1.19–6.56; P = 0.009).

Conclusion

Anti‐CCP antibodies in patients with RA are independently associated with the development of ischemic heart disease.     

Negative association between smoking and anti-saccharomyces cerevisiae antibodies in Crohn's disease

BACKGROUND: Crohn's disease (CD) is a polygenic multifactorial heterogeneous disease. Anti-Saccharomyces Cerevisiae antibodies (ASCA) correlate highly with CD and are present in 50-80% of patients. The reason for ASCA positivity or negativity in CD is unknown. The aim of our work was to analyse clinical, epidemiological and genetic characteristics in ASCA+ or ASCA- CD patients. METHODS: 113 patients with CD were tested for ASCA (IgA and IgG) by using a commercial kit (Medipan Diagnostica). Age, gender, systemic manifestations, familial form of disease, age at diagnosis, location and behaviour of the disease, smoking habit as well as genotyping for -308 TNF gene polymorphisms were determined. RESULTS: 38.9% CD patients were negative for both IgA and IgG ASCA while 61.1% were ASCA positive (respectively IgA and IgG: 31.9%; IgA only: 9.7%; IgG only: 19.5%). The only significant difference between ASCA+ and ASCA- patients was for smoking habit: there were 29% smokers in ASCA+ versus 50% in ASCA- CD patients (P = 0.03). This low proportion of smokers was more prominent in ASCA IgA+ patients than in isolated ASCA IgG+ patients (25.6% versus 45.5%) and was minimal in patients with high titers of ASCA IgA (0/8). Logistic regression showed smoking habit still borderline for significance (P = 0.057). CONCLUSIONS: Our results suggest a negative association between smoking and ASCA positivity in CD. This association was more prominent for ASCA IgA+. It indicates that smoking habit should be taken into account when analysing ASCA status in CD patients and may suggest an influence of smoking on immunization against intestinal material.     

Smoking habit and cardiovascular diseases

The relationship between smoking and ischemic heart disease was discussed, in terms of the smoking habit and the mechanisms of acute and chronic effects of smoking on the cardiovascular system as one of the coronary risk factors, with reference to exercise capacity and coronary flow reserve. The smoking habits of 1000 consecutive patients with ischemic heart disease, who were evaluated with coronary angiography, were analyzed. High percentages of smokers were observed in the younger generation. It was up to 86% in the 4th decade, though it was only 48% in the 8th decade. There was no large difference in other risk factors between smokers and non-smokers. The exercise capacity with and without smoking was evaluated with treadmill exercise test in 6 healthy volunteers. The exercise time was decreased with smoking, compared to without smoking, indicating a decrease in exercise capacity due to smoking. The elevated concentration of carbon monoxide in blood decreased the ability of oxygen transport. The increased lactic acid level in blood with smoking suggested anaerobic energy production acting as a part of the energy source. The smoking increased the myocardial oxygen consumption in relation to increase in heart rate and blood pressure. It decreased coronary flow reserve, shown by a peak to resting flow velocity ratio measured with the Doppler flow velocimeter. In coronary heart disease, therefore, the threshold of myocardial ischemia was decreased by smoking. The decrease in coronary flow reserve recovered with cessation of smoking for more than 2 days.     

Lipid peroxides and atherosclerosis. The enzymatic detoxication of lipid peroxides in the blood in ischemic heart disease due to coronary artery arteriosclerosis]

It was established that in blood of patients with ischemic heart disease due to atherosclerosis of the coronary arteries (the diagnosis was verified in selective coronaroangiography) the content of acylhydroperoxides grows while the activity of glutathione-peroxidase II decreases. In blood of patients with no damage to the coronary vessels (according to the results of angiography), glutathione-peroxidase II activity does not differ significantly from the values in the control group. The decrease of glutathione-peroxidase II activity was most marked in patients with ischemic heart disease and hypercholesterolemia. It is suggested that the increase in the peroxide content in blood of patients with ischemic heart disease may be due to the sharp decrease in the activity of glutathione-peroxidase II.     

Trends, risk factors, and prevention of ischemic heart disease in Japan

The mortality from ischemic heart disease has increased steadily in most industrialized countries from the 19th century up to 1970. In some developed countries, such as the U.S.A. and Australia, it started to decrease in the nineteen seventies and accelerated recently. However, it has increased in some East European countries, such as Rumania, Poland and Hungary. The mortality had been extraordinarily low and the age standardized rate declined since the nineteen seventies in our country as in the U.S.A. These finding strongly suggests the possibility of prevention of ischemic heart disease worldwide. Among the risk factors, hypertension has gradually decreased due to treatment and lower intake salt in Japan. However, the compliance of antihypertensive treatment could be improved and the average intake of salt further decreased. The frequency of hypercholesterolemia was quite low for many years, but increased recently in Japan. However, the national average level of serum cholesterol is probably close to 200 mg/dl, and the new cholesterol level data will be revealed by the national survey in 1990. The world-famous high figure of smoking among Japanese men has been declining for these 20 years down to 61.2% in 1988, along with an exceptionally low rate for women in industrialized countries. The average figure of body weight by stature was in line with the desirable body weight for Japanese and the average intake of lipids has leveled off recently according to the National Nutrition Survey. After all it can be concluded that incidence of ischemic heart disease could be reduced further, even in Japan.