Vascular Disease Mortality Research Articles

Neutrophil Count and Complex Lesions in Patients With Coronary Artery Disease

To the Editor: In a recent article, Coller1 reviews the role of leukocytosis in vascular disease morbidity and mortality. Despite the exhaustive nature of the review, we were concerned that the author failed to address an issue of major importance, namely the relationship between neutrophil count and the presence of vulnerable atheromatous plaques in patients with coronary artery disease. Acute coronary syndromes result mainly from occlusive coronary artery thrombosis at sites of plaque fissure, rupture, or superficial erosion. At angiography, disrupted or ulcerated plaques often appear as “complex” stenoses with rough …

Prevalence of Abnormal Glucose Tolerance Following a Transient Ischemic Attack or Ischemic Stroke

Despite current preventive therapies, patients with transient ischemic attack (TIA) and ischemic stroke remain at high risk for recurrent brain disease and cardiovascular events. In an effort to develop new therapies, abnormal glucose tolerance has recently been proposed as an interventional target. Among persons not otherwise known to be diabetic, impaired glucose tolerance (IGT) and diabetic glucose tolerance (DGT) are each associated with an increased risk for incident vascular disease, vascular disease mortality, and all-cause mortality. We conducted this study to determine if IGT and DGT are sufficiently common among patients with TIA and ischemic stroke to warrant therapeutic trials of antihyperglycemic agents. Men and women older than 45 years were recruited from 3 hospitals in south central Connecticut. Eligibility criteria included a recent TIA or nondisabling ischemic stroke, no history of physician-diagnosed diabetes mellitus, and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). After an overnight fast, subjects were admitted to a clinical research center for a standard 75-g oral glucose tolerance test. Impaired glucose tolerance was defined by a 2-hour plasma glucose value of 140 to 199 mg/dL (7.8-11.0 mmol / L) and DGT by a value of 200 mg/dL or greater (> or =11.1 mmol/L). Between June 2000 and August 2003, we enrolled 98 eligible patients. The average time from TIA or stroke to measurement of glucose tolerance was 105 days (range, 24-180 days) and the median age was 71 years. Twenty-seven subjects (28%) had IGT and 24 (24%) had diabetes. In a forward stepwise logistic regression model, only a fasting plasma glucose level of 110 mg/dL or greater (> or =6.1 mmol / L) and lower waist circumference were associated with an increased risk for IGT or DGT. Impaired glucose tolerance and DGT are present in most persons with a recent TIA or ischemic stroke who have no history of diabetes and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). Our findings bring new urgency to the initiation of research to examine the effectiveness of antihyperglycemic therapies among patients with cerebrovascular disease and abnormal glucose tolerance.

Leukocytosis and Ischemic Vascular Disease Morbidity and Mortality

The association between leukocytosis and increased morbidity and mortality of ischemic vascular disease has been observed for more than half a century, and recent studies in >350,000 patients confirm the robustness of the association and the dramatically higher relative and absolute acute and chronic mortality rates in patients with high versus low leukocyte counts. Although there is reason to believe that the association is not causal (that is, that leukocytosis is simply a marker of inflammation), there is also reason to believe that the leukocytosis directly enhances acute thrombosis and chronic atherosclerosis. Leukocytosis also is associated with poor prognosis and vaso-occlusive events in patients with sickle cell disease, and experimental data suggest a direct role for leukocytes in microvascular obstruction. The only way to test whether leukocytes contribute directly to poor outcome in ischemic cardiovascular disease is to assess the effect of modifying leukocyte function or number. Because selective blockade of leukocyte integrin alphaMbeta2 and P-selectin have thus far been disappointing as therapeutic strategies in human cardiovascular and cerebrovascular disease, I discuss the potential risks and benefits of short-term treatment with hydroxyurea to decrease the leukocyte count in select populations of patients at the highest risk of short-term death.

1160 Asymptomatic intracranial atherosclerosis independently predicts total and vascular disease mortality in type 2 diabetic patients in Chinese

1160 Asymptomatic intracranial atherosclerosis independently predicts total and vascular disease mortality in type 2 diabetic patients in Chinese

Peripheral vascular disease and one-year mortality following percutaneous coronary revascularization

The association between peripheral vascular disease and outcomes after percutaneous coronary intervention was examined in the Do Tirofiban and Reopro Give Similar Efficacy Outcome Trial (TARGET). After adjustments in a multivariate model, a history of peripheral vascular disease was found to be associated with a two- to threefold increase in mortality at 1 year after coronary stent placement.

Air Pollution and Daily Mortality in Two U.S. Counties: Season-Specific Analyses and Exposure-Response Relationships

I used generalized additive models to analyze the time series of daily total nonaccidental deaths and deaths due to vascular disease over the period 1987-1995 in two major metropolitan areas, Cook County, Illinois, and Los Angeles County, California, in the United States. In both counties I had monitoring information on PM 10, CO, SO 2, NO 2, and O 3. In Los Angeles, monitoring information on PM 2.5 was available as well. In addition to full-year analyses, I performed season-specific analyses. I present the results of both single- and multipollutant analyses. Although components of air pollution were associated with total nonaccidental and vascular disease mortality in both counties, the results indicate considerable heterogeneity of these associations in the two locations and also from season to season. In Los Angeles County, the gases, particularly CO and SO 2 but not ozone, were more strongly associated with mortality than was particulate matter, which exhibited only weak and inconsistent associations with both mortality endpoints. Both PM 10 and the gases were associated with total and vascular disease mortality in Cook County. The association of the gases with both mortality endpoints appeared to be stronger and more robust than that of PM 10. Exposure-response analyses using flexible smoothers showed significant departures from linearity, particularly for PM effects.

Prevention of hypertension and its complications: theoretical basis and guidelines for treatment.

Hypertension is a nutritional-hygienic disease. Long-term caloric intake in excess of energy expenditures, chronic supraphysiological intake of dietary sodium, excessive alcohol consumption, and psychosocial stressors all contribute to the development of hypertension throughout the world. Elevated BP, particularly systolic BP, has been linked to multiple adverse clinical outcomes including stroke, heart failure, myocardial infarction, renal insufficiency/failure, peripheral vascular disease, retinopathy, dementia, and premature mortality. These undesirable clinical outcomes are typically, although not invariably, preceded by pressure-related target-organ injury such as left ventricular hypertrophy, renal insufficiency and proteinuria. The relation of BP and CKD and, in turn, the prevention of CKD or forestalling its progression by hypertension treatment, will be the focus of this manuscript. In hypertensive persons with reduced kidney function and/or proteinuria, lowering BP with multidrug therapy that is inclusive of pharmacologic modulators of the renin-angiotensin-aldosterone-kinin system is an effective strategy to forestall the progressive loss of kidney function. The totality of data support low therapeutic BP targets for persons with proteinuria >1 g/d. Nevertheless, in persons with CKD, even those with proteinuria below the dipstick positive level (approximately 300 mg/d or urine protein to creatinine ratio of 0.22), aggressive BP control also may be warranted because of the high risk of nonrenal cardiovascular disease. Multiple antihypertensive drugs will be required in the vast majority of patients with diabetes and/or reduced kidney function to attain BP goal. Renin-angiotensin system (RAS) modulator therapy is indicated among persons with diabetes mellitus and CKD. Available data support the use of angiotensin receptor blockers in persons with type 2 diabetes and overt nephropathy for preservation of kidney function. Among persons with type I diabetes with or without overt nephropathy, type 2 diabetes without overt nephropathy and in nondiabetic CKD, the available clinical data support the use of angiotensin-converting enzyme inhibitors as the RAS modulator of choice. Low therapeutic target BP levels <130/80 mmHg in persons with type 2 diabetes mellitus also appear warranted based on available data mostly for reducing the risk of nonrenal cardiovascular disease and overall mortality.

Protein S declines during winter respiratory infections

There is an increase in cardiovascular and cerebrovascular morbidity and mortality in the older adult population during the winter that could be related to prothrombotic changes caused by seasonal effects or acute respiratory tract infections. Therefore, a prospective cohort study was conducted to assess the effect of acute winter respiratory infection on hemostatic parameters including complement 4b-binding protein (C4-BP), functional protein S, total protein S, free protein S, and the inflammatory marker, interleukin-6 (IL-6), in younger and older adults. The changes in the levels of hemostatic and inflammatory markers during winter respiratory infections in the younger and older adults were compared with matched, non-infected controls. In younger and older adults (combined), total protein S increased from 83% [95% confidence interval (CI); 77-88] to 98% (95% CI; 91-106, P < 0.001) while free protein S decreased from 100% (95% CI; 95-105) to 70% (95% CI; 66-75, P < 0.001). There were no significant changes in C4-BP (P = 0.622), functional protein S (P = 0.061) or IL-6 (P = 0.651) from baseline. In a multivariate analysis, only total protein S and free protein S showed significant association with seasonal change after adjusting for the effect of infection. The estimated effect of season on total protein S was 15 +/- 4%, P < 0.001 and on free protein S was -27 +/- 3%, P < 0.001. After adjusting for seasonal effect, only functional protein S showed a significant association with infection, with the estimated effect of -17 +/- 5%, P < 0.001. The results in the younger and older adults were similar to those in the combined groups. Seasonal and infection-related changes in hemostatic parameters including an increase in fibrinogen and a decrease in free protein S, observed in this study, may contribute to thrombotic risk and excess vascular disease morbidity and mortality in older populations in the winter season.

Air Pollution and Daily Mortality in Two U.S. Counties: Season-Specific Analyses and Exposure-Response Relationships

I used generalized additive models to analyze the time series of daily total nonaccidental deaths and deaths due to vascular disease over the period 1987-1995 in two major metropolitan areas, Cook County, Illinois, and Los Angeles County, California, in the United States. In both counties I had monitoring information on PM 10, CO, SO 2, NO 2, and O 3. In Los Angeles, monitoring information on PM 2.5 was available as well. In addition to full-year analyses, I performed season-specific analyses. I present the results of both single- and multipollutant analyses. Although components of air pollution were associated with total nonaccidental and vascular disease mortality in both counties, the results indicate considerable heterogeneity of these associations in the two locations and also from season to season. In Los Angeles County, the gases, particularly CO and SO 2 but not ozone, were more strongly associated with mortality than was particulate matter, which exhibited only weak and inconsistent associations with both mortality endpoints. Both PM 10 and the gases were associated with total and vascular disease mortality in Cook County. The association of the gases with both mortality endpoints appeared to be stronger and more robust than that of PM 10. Exposure-response analyses using flexible smoothers showed significant departures from linearity, particularly for PM effects.

Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: a prospective study.

Calcification complications are frequent among long-term dialysis patients. However, the prognostic implication of cardiac valve calcification in this population is not known. This study aimed to determine if cardiac valve calcification predicts mortality in long-term dialysis patients. Baseline echocardiography was performed in 192 patients (mean +/- SD age, 55 +/- 12 yr) on continuous ambulatory peritoneal dialysis (mean +/- SD duration of dialysis, 39 +/- 31 mo) to screen for calcification of the aortic valve, mitral valve, or both. Valvular calcification was present in 62 patients. During the mean follow-up of 17.9 mo (range, 0.6 to 33.9 mo), 46 deaths (50% of cardiovascular causes) were observed. Overall 1-yr survival was 70% and 93% for patients with and without valvular calcification (P < 0.0001, log-rank test). Cardiovascular mortality was 22% and 3% for patients with and without valvular calcification (P < 0.0001). Multivariable Cox regression analysis showed that cardiac valve calcification was predictive of an increased all-cause mortality (hazard ratio [HR], 2.50; 95% CI, 1.32 to 4.76; P = 0.005) and cardiovascular death (HR 5.39; 95% CI, 2.16 to 13.48; P = 0.0003) independent of age, male gender, dialysis duration, C-reactive protein, diabetes, and atherosclerotic vascular disease. Eighty-nine percent of patients with both valvular calcification and atherosclerotic vascular disease, 23% of patients with valvular calcification only, 21% of patients with atherosclerotic vascular disease only, and 13% of patients with neither complication died at 1-yr (P < 0.0005). The cardiovascular death rate was 85% for patients with both complications, 13% for patients with valvular calcification only, 14% for patients with atherosclerotic vascular disease only, and 5% for those with neither complication (P < 0.0005). The number of calcified valves was associated with all-cause mortality (P < 0.0005) and cardiovascular death (P < 0.0005). One-year all-cause mortality was 57% for patients with both aortic and mitral valves calcified, 40% for those with either valve calcified, and 15% for those with neither valve calcified. In conclusion, cardiac valve calcification is a powerful predictor for mortality and cardiovascular deaths in long-term dialysis patients. Valvular calcification by itself has similar prognostic importance as the presence of atherosclerotic vascular disease. Its coexistence with other atherosclerotic complications indicates more severe disease and has the worst outcome.

Arterial calcification in diabetes.

Diabetes is associated with an increased prevalence of atherosclerotic vascular disease and cardiovascular mortality. In diabetic patients, medial calcification appears to be a strong independent predictor of cardiovascular mortality, it occurs particularly in those with neuropathy. Recent evidence suggests that medial calcification in diabetes is an active, cell-mediated process, similar to that observed in patients with end-stage renal disease (ESRD), in which vascular smooth muscle cells (VSMCs) express a number of bone matrix proteins that act to either facilitate or regulate the calcification process. Several bone-associated proteins (e.g., osteopontin, bone sialoprotein, alkaline phosphatase, type 1 collagen, osteocalcin) have been demonstrated in histologic sections of vessels obtained from patients with diabetes or ESRD. In in vitro experiments, high glucose induced cell proliferation and expression of osteopontin in cultured VSMCs. Hypoxia had additive effects of hyperglycemia on VSMCs. In addition, uremic serum upregulates osteoblast transcription factor Cbfa 1 and osteopontin expression in cultured VSMCs. The pathogenesis of vascular calcification in diabetes is not completely understood, although high glucose and other potential factors may play an important role by transforming VSMCs into osteoblast-like cells. Further understanding of the mechanism by which diabetes induces this complication is needed to design effective therapeutic strategies to intervene with this process.

Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure

Background: Elevated total plasma homocysteine (tHcy) levels have been associated with vascular disease and higher mortality in patients with coronary artery disease. Graft coronary disease is a major cause of mortality in long-term survivors of heart transplantation, and hyperhomocysteinemia may be one of its causes. The objectives of our study were to establish the effectiveness of a 3 stage homocysteine-lowering algorithm in a group of 84 heart transplant (HTx) patients and to evaluate the effect of renal function on the response to homocysteine-lowering therapy. Methods Prospective treatment of 84 Htx patients (64 male; mean age, 48 ± 13 years) with tHcy > 75th percentile consisted of a 3-stage treatment algorithm: Stage 1, folic acid (FA) 2 mg + vitamin (vit) B 12 500 mcg daily; Stage 2, addition of vit B 6 100 mg daily; Stage 3, increase FA to 15 mg daily. Serum creatinine (Cr) and tHcy levels were measured before treatment and 21 ± 19 weeks after each stage of treatment. Results All 3 stages of treatment significantly lowered mean tHcy from 22.4 ± 16.3 (mean ± SD) μmol/liter to 16.3 ± 6.7 μmol/liter ( p < 0.00001), from 17.6 ± 6.1 μmol/liter to 15.2 ± 5.3 μmol/liter ( p < 0.0001), and from 16.8 ± 5.2 μmol/liter to 15.6 ± 5.3 μmol/liter ( p < 0.05), respectively. The average reduction from baseline was 38%. Creatinine levels did not change significantly during the study period. Total plasma homocysteine levels decreased below the 75th percentile in 55% of patients, with Cr levels significantly lower in this group of patients (126 ± 36 μmol/liter vs 182 ± 65 μmol/liter, p < 0.00001). However, we found no significant relationship between % change in tHcy and baseline Cr. Conclusions In a group of 84 heart transplant patients with tHcy levels >75th percentile, treatment with FA and vit B 6 and B 12 according to a 3-stage algorithm resulted in statistically significant declines in mean tHcy levels. Overall, tHcy levels decreased 38%, with target tHcy levels <75th percentile achieved in 55% of the patients. The % change in tHcy was not related to Cr. Further studies are needed to correlate treatment of hyperhomocysteinemia with clinical endpoints, such as the time to development of transplant vasculopathy and long-term survival, and to define the most appropriate targets for therapy.

Platelet Function Inhibitors in the Year 2000

SummaryPlatelet thrombi are responsible for much of the morbidity and mortality of arterial vascular disease (1). Because platelet inhibitors such as aspirin have proven to be of benefit to patients with these disorders, there has been a directed search for more potent anti-platelet agents. The following discussion addresses the mechanism of action and clinical utility of the currently available platelet function inhibitors. Although in theory these agents could impair platelet adhesion, aggregation, secretion, or platelet procoagulant activity, in practice they are focused almost exclusively on the biochemical events that proceed from platelet stimulation to ligand binding to the platelet fibrinogen receptor GPIIb-IIIa.

Stress and Hypertension

Hypertension is a major cardiovascular risk factor that directly contributes to myocardial infarction,cerebrovascular accidents, congestive cardiac failure, peripheral vascular disease and premature mortality (I). In the great majority of cases, no cause can be found and this form of hypertension is termed 'primary' or 'essential' hypertension. Various theories have been put forward and the causes can be divided broadly into genetic and environmental factors. Based on twin studies, it was estimated that about 50 percent of blood pressure variance is genetic (2). The main environmental causes are dietary and psychosocial factors. In this review, we will concentrate on the latter while notingthat there is still disagreement about the role of a dietary factor, sodium chloride, in causing hypertension. A metaM analysis of trials of sodium restriction concluded that sodium intake had no influence on blood pressure in normotensive subjects and in hypertensives below 45 years of age (3). We will also discuss an interesting phenomenon known as 'white coat hypertension'.

Effect of MTHFR 677C>T on plasma total homocysteine levels in renal graft recipients

Hyperhomocysteinemia is an established, independent risk factor for vascular disease morbidity and mortality. The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T has been shown to result in increased total homocysteine concentrations on the basis of low folate levels caused by a decreased enzyme activity. The effect of this polymorphism on total homocysteine and folate plasma levels in renal transplant patients is unknown. We screened 636 kidney graft recipients for the presence of the MTHFR C677T gene polymorphism. The major determinants of total homocysteine and folate plasma concentrations of 63 patients, who were identified to be homozygous for this gene polymorphism compared with heterozygotes (N = 63), and patients with wild-type alleles (N = 63), who were matched for sex, age, glomerular filtration rate (GFR), and body mass index, were identified by analysis of covariance. The variables included sex, age, GFR, body mass index, time since transplantation, folate and vitamin B12 levels, the use of azathioprine, and the MTHFR genotype. To investigate the impact of the kidney donor MTHFR genotype on total homocysteine and folate plasma concentrations, a similar model was applied in 111 kidney graft recipients with stable graft function, in whom the kidney donor C677T MTHFR gene polymorphism was determined. The allele frequency of the C677T polymorphism in the MTHFR gene was 0.313 in the whole study population [wild-type (CC), 301; heterozygous (CT), 272; and homozygous mutant (TT), 63 patients, respectively] and showed no difference in the patient subgroups with various renal diseases. The MTHFR C677T gene polymorphism significantly influenced total homocysteine and folate plasma concentrations in renal transplant recipients (P = 0.0009 and P = 0.0002, respectively). Furthermore, a significant influence of the GFR (P = 0.0001), folate levels (P = 0.0001), age (P = 0.0001), body mass index (P = 0.0001), gender (P = 0.0005), and vitamin B12 levels (P = 0.004) on total homocysteine concentrations was observed. The donor MTHFR gene polymorphism had no influence on total homocysteine and folate levels. Geometric mean total homocysteine levels in patients homozygous for the mutant MTHFR allele were 18.6 micromol/liter compared with 14.6 micromol/liter and 14.9 micromol/liter in patients heterozygous for the MTHFR gene polymorphism and those with wild-type alleles (P < 0.05 for TT vs. CT and CC). Geometric mean folate levels were lower in CT and TT patients (11.2 and 10.2 nmol/liter) compared with CC patients (13.6 nmol/liter, P < 0.05 vs. CT and TT). This study demonstrates that homozygosity for the C677T polymorphism in the MTHFR gene significantly increases total homocysteine concentrations and lowers folate levels in kidney graft recipients, even in patients with excellent renal function (GFR more than median). These findings have important implications for risk evaluation and vitamin intervention therapy in these patients who carry an increased risk for the development of cardiovascular disease.

Blood vitamins, mineral elements and inflammation markers as risk factors of vascular and non-vascular disease mortality in an elderly population.

The need for protecting agents against degenerative processes of the body has been proposed to be especially high in elderly people. In order to evaluate the prognostic value of various biochemical factors in ageing the associations of blood concentrations of several vitamins, mineral elements and some other suggested risk factors with vascular and non-vascular mortality were studied in an elderly population. A large health survey with complete clinical evaluation was carried out in the City of Turku in 1982-1983. A random sample of 344 community-living elderly individuals aged 65 years or older, stratified into four age groups, was studied. During the 13 years follow-up 225 subjects had died. Calcium, magnesium, copper, ceruloplasmin, zinc, selenium, iron, ferritin, transferrin, alpha-tocopherol, retinol, folate, vitamin B12, malondialdehyde, orosomucoid and insulin levels were analysed from the blood specimens. The relations between the compounds measured and relative mortality risks during the 13-year follow-up were analysed by Cox proportional hazards model adjusting for other known risk factors. High concentrations of serum copper, orosomucoid and insulin were associated with increased risk of vascular mortality. The relative risks within the subjects of the highest tertile of serum concentrations were 2.2 for copper, 1.8 for orosomucoid, and 1.8 for insulin when adjusted for many confounding risk factors. Low serum vitamin B12 concentrations appeared to be significantly (P = 0.01) associated with increased vascular mortality. The associations were essentially not more significant when adjusted only for age. Contrary to earlier observations concentrations of serum magnesium, selenium, alpha-tocopherol, iron and its binding proteins or plasma and erythrocyte folate were not associated with increased mortality risk when adjusted for confounding risk factors. The authors suggest that in elderly subjects these elements and compounds are at the most weak, and probably non-independent risk factors for vascular mortality.

Folate status, vascular disease and cognition in elderly Canadians.

To report on the relationship between serum folate levels and the prevalence of stroke, peripheral vascular disease, cognitive problems and short-term mortality in elderly people. 1171 subjects whose serum folate was determined as part of their clinical examination in the Canadian Study of Health and Aging, a population study of individuals 65 years and older. Cross-sectional analysis compared relationships between serum folate levels and clinical features; longitudinal analysis examined mortality at follow-up by folate status at the time of the clinical examination. Membership in the lowest quartile for serum folate was associated with an increased likelihood of stroke. Those with low folate levels were more likely to be demented, institutionalized and depressed. In the cognitively impaired but not demented group, those with low folate levels scored lower on the Modified Mini Mental State and had more short-term memory problems. Low folate level was a significant explanatory variable for stroke. Low folate levels were common in all types of dementia and were associated with a history of weight loss, lower body mass index and lower serum albumin concentrations. This may reflect the reduced ability of cognitively impaired individuals to eat adequately.

Medical education on tobacco: implications of a worldwide survey. Tobacco and Health Committee of the International Union against Tuberculosis and Lung Disease (IUATLD).

This report considers the implications for medical education of a global survey of the knowledge, behaviour and attitudes of medical students regarding tobacco. This was conducted in 42 countries derived from all continents. A total of 9326 students (44% women) from 51 medical schools replied anonymously to a multiple choice questionnaire administered in the local language. Student smoking rates varied greatly between countries/regions: daily smoking in men from 2% (Australia) to 48% (one centre in the former USSR); in women from nil in some Asian medical schools to 22% in one European. Though there was some variation between countries and medical schools, there was widespread ignorance of the causal role of smoking in specific diseases; notably coronary artery disease, peripheral vascular disease, emphysema, bladder cancer and neonatal mortality. There were widespread defects in knowledge and motivation regarding counselling patients to quit smoking, with a common failure to appreciate a doctor's responsibilities in prevention. Very few students knew the value of tobacco taxation in reducing consumption. Following our survey we were asked to advise the World Health Organization on a summary of the desirable tobacco content of medical curricula, which has now been issued. The International Union against Tuberculosis and Lung Disease, in cooperation with the European Region of WHO, has circulated the Deans of all European medical schools with a summary of the deficiencies revealed by the European component of the survey, together with a questionnaire on proposed action. A similar initiative is being considered in cooperation with the Western Pacific Region of WHO.

Smoking habits and attitudes of medical students towards smoking and antismoking campaigns in nine Asian countries. The Tobacco and Health Committee of the International Union Against Tuberculosis and Lung Diseases.

As part of a world survey of the habits, knowledge and attitudes of medical students regarding tobacco we report a study in 15 medical schools from nine Asian countries. Some 1646 first year and 1587 final year students were included, of whom 59% were male. The prevalence of daily smoking in males was 4% in first year and 11% in final year; of occasional smoking 18% and 24% respectively, both with considerable variations between countries. The rates were very low in women. Male exsmokers varied from 3% to 24% in different centres. Overall, 33% of smokers had made a serious attempt to quit; 44% expected to have succeeded within 5 years. Over 80% of non- or exsmokers, but only 60% of smokers, thought smoking was harmful to health. There was gross underestimation of tobacco's causal role in a number of important diseases, e.g. coronary artery disease, peripheral vascular disease, emphysema, bladder cancer and neonatal mortality. There were notable defects both in training and in motivation to counsel smoking patients. There was only partial knowledge of legislative and other measures to discourage smoking, e.g. only 44% of final year students (26% of smokers) thought increased taxation an important measure. In knowledge and attitudes there was little difference between the sexes, but in most aspects smokers had notably lower scores.

Influence of dietary fish oil on arterial thrombosis and atherosclerosis in animal models and in man

In animal models of arterial thrombosis, fish-oil-enriched diets have been shown to have an antithrombotic effect. There is strong evidence, however, that this only holds if the fish-oil consumption is associated with a reduction of the saturated fat intake. In animal models of atherosclerosis the effect of a marine diet is not consistent. Although in some studies with cod-liver oil (which is relatively low in saturated fatty acids) a beneficial effect is observed, studies with other, more saturated fish oils do not confirm this. The influence of fish-oil consumption on some thrombotic complications of human atherosclerosis is not well documented. So far, the few results reported are not very promising, but it should remembered that this mainly concerns short-term studies. Studies with respect to human fibrinolysis are equivocal. Evidence has been obtained that fish consumption may even have an adverse effect on certain aspects of the fibrinolytic process. The studies performed so far do not provide conclusive evidence as to the importance of fish- and fish-oil-enriched food for prevention and therapy of ischaemic cardiovascular disease. Further research is needed, especially with long-term, high-quality animal models. Moreover, long-term, well-controlled, prospective human intervention studies are required to investigate the effect of feasible fish(oil)-enriched diets on morbidity and mortality of ischaemic cardiac and vascular diseases.