Research Database –
International Updates

Heart

Issue 93

MIWA and colleagues, Department of Autonomic and Behavioral Neurosciences, Division of Higher Nervous Control, Research Institute of Environmental Medicine, Nagoya University, Nagoya, have described the human cardiovascular responses to a 60-minute bath at 40°C.
Background: The study was designed to determine human cardiovascular responses to a 60-minute bath at 40°C compared with a thermoneutral bath at 34.5°C.
Methods: Mean blood pressure, heart rate, skin blood flow, and core temperature were measured in 8 healthy young men bathing at two different temperatures, 34.5°C and 40°C.
Results: During the thermoneutral bath, heart rate tended to decrease and all other variables showed no significant changes. Ten minutes after entering the hot bath, mean blood pressure decreased while heart rate and skin blood flow increased. At the same time, core temperature increased.
Conclusions: The authors conclude that bathing at 40°C may induce remarkable changes in the cardiovascular system by raising core temperature when the bath lasts for more than 10 minutes.
Miwa C, Matsukawa T, Iwase S, Sugiyama Y, Mano T, Sugenoya J, Yamaguchi H, Kirsch KA.. Human cardiovascular responses to a 60-min bath at 40 degrees C. Environmental Medicine 38 (1): 77-80, 1994.

VASDEV and co-workers, Department of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada, svasdev@mun.ca, have found that dietary vitamin C and E supplementation prevents fructose-induced hypertension in rats.

Background: Hypertension can be induced in rats by fructose (fruit sugar). In this condition, an excess of certain endogenous oxidants (aldehydes) is found, and this leads to a variety of pathological molecular and cellular changes. The aim of this study was to test whether this process could be prevented by the administration of the antioxidant vitamins C and E.
Methods: Animals were divided into 4 groups and treated as follows: Control group, normal diet and drinking water; fructose group, normal diet and 4% fructose in drinking water; vitamin E group, diet supplemented with vitamin E and 4% fructose in drinking water; vitamin C group, diet supplemented with vitamin C and 4% fructose in drinking water. After 7 weeks, systolic blood pressure and a variety of other clinical parameters were measured in all groups.
Results: Animals in the fructose group displayed signs of hypertension including elevated systolic blood pressure and elevated platelet calcium, as well as signs of oxidative damage in the aorta and kidneys, and smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin C and E prevented all these changes.
Conclusions: The antioxidant vitamins C and E, administered in moderate doses, prevented hypertension and oxidative damage to kidneys and blood vessels associated with this in rats.
Vasdev S, Gill V, Parai S, Longerich L, Gadag V. Dietary vitamin E and C supplementation prevents fructose induced hypertension in rats. Molecular and Cellular Biochemistry 241 (1-2): 107-114, Dec 2002.

Issue 91

CAPITA and ALONSO-CALLEJA, Escuela Superior y Technica de Ingenieria Agraria (ESTIA), Universidad de Leon, Avda. Astorga s/n, 24400 Ponferrada, Leon, Spain, have studied the intake of nutrients associated with an increased risk of cardiovascular disease in a Spanish population.
Background: The aim of the study was to determine the daily intake of nutrients associated with increased risk of cardiovascular disease.
Methods: Nutrient intake data of 100 people in Leon, northwestern Spain, aged between 20 and 40 years were obtained from seven non-consecutive daily food records.
Results: Average energy intake was 2906 kcal among men and 2107 kcal among women. Total fat accounted for 39.21% in men and 38.96% in women. Average saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids were 13.03%, 15.51% and 6.22% in men, and 12.20%, 15.58% and 7.10% in women. Essential fatty acid amounts were adequate. The ratio of n-6 to n-3 polyunsaturated fatty acids was 7.14 (men) and 8.33 (women). High cholesterol intake was found (441 mg for men and 359 mg for women). Dinner showed the highest densities of fat and cholesterol, while breakfast had the highest densities of saturated fatty acids and trans-fatty acids.
Conclusions: The results advise a decrease of total fat, saturated fatty acids, n-6 polyunsaturates, cholesterol, and sodium. In contrast, energy intake and consumption of dietary fibre, vitamins A and E and selenium should be increased in the study population.
Capita R, Alonso-Calleja C. Intake of nutrients associated with an increased risk of cardiovascular disease in a Spanish population. International Journal of Food Sciences and Nutrition 54 (1): 57-75, Jan 2003.

HU and colleagues, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, Mass 02115, USA, frank.hu@channing.harvard.edu, have investigated the link between fish and n-3 polyunsaturated fatty acid consumption and coronary heart disease in diabetic women.
Background: Although it seems clear that there is an inverse association between the intake of fish containing n-3 polyunsaturated fatty acids and coronary heart disease, only limited data are available for diabetes patients.
Methods: In this prospective study, the association between intake of fish and n-3 fatty acids and risk of coronary heart disease and mortality was studied among 5103 women with diagnosed type II diabetes but free of cardiovascular disease or cancer at baseline. Between 1980 and 1996, 141 deaths from coronary heart disease and 221 nonfatal myocardial infarctions were recorded in the study population.
Results: Compared to women who ate fish less than once a month, the relative risks of coronary heart disease were 0.70 for fish 1 to 3 times a month, 0.60 for fish once a week, 0.64 for fish 2 to 4 times a week, and 0.36 for fish at least 5 times a week (p for trend 0.002). Higher consumption of fish was also associated with significantly lower mortality. Higher consumption of n-3 polyunsaturates was associated with a trend towards lower incidence of coronary heart disease and lower mortality.
Conclusions: A higher consumption of fish was associated with a lower risk of coronary heart disease and total mortality among diabetic women.
Hu FB, Cho E, Rexrode KM, Albert CM, Manson JE. Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Circulation 107 (14): 1852-1857, Apr 2003.

Issue 90

BROWN and GOODMAN, University of Florida, College of Nursing, J. Hillis Miller Health Sciences Center, Gainesville, Florida, USA, have reviewed (65 references) vitamins A, C, and E, and their relationship to cardiovascular disease.
Background: Certain modifications in low density lipoproteins (LDL) are thought to be a major pathogen for cardiovascular disease. These have in the last 10 years been linked to oxidative damage by free radicals, and as a consequence numerous trials have been conducted to try and prevent these modifications with antioxidant vitamins.
Results and Conclusions: This report summarizes the major findings of cardiovascular disease-related epidemiological research and clinical trials conducted in the past 5 years on vitamins A, C, and E. In prospective studies, the supplementation with vitamins A, C, and E has been correlated with lower mortality rates from cardiovascular disease. When recent clinical trials and oxidation studies are analyzed, the weight of the evidence suggests that 100 – 400 IU of daily vitamin E over two years or more may positively influence mortality rates. People with hypertension or diabetes and smokers may also benefit from extra vitamin C.
Brown DJ , Goodman J. A review of vitamins A, C, and E and their relationship to cardiovascular disease. Clinical Excellence for Nurse Practitioners 2 (1): 10-22, Jan 2003.

SKERRETT and HENNEKENS, Harvard Health Publications, Harvard Medical School, Boston, MA, USA, have reviewed (35 references) the consumption of fish and fish oil and the risk for stroke.
Background: Consumption of fish and fish oil has long been associated with a decreased risk for stroke.
Results: Cross-sectional and case-control studies have generally shown an inverse association between the consumption of fish and fish oil and the incidence of stroke. Results from prospective studies have been less consistent, with one study showing no association, one showing a
possible inverse association, and three showing a significant inverse association. A significant decrease of thrombotic stroke was found among women who ate fish at least twice a week as compared to those who ate fish less than once a month. No association was found in the same study between consumption of fish and risk for haemorrhagic stroke.
Conclusions: These data support the finding that eating fish three times a week reduces the risk of thrombotic stroke.
Skerret PJ, Hennekens CH. Consumption of fish and fish oils and decreased risk of stroke. Preventive Cardiology 6 (1): 38-41, Winter 2003.
Comment: These results are highly interesting and may have immense impact if consumption of fish and fish oil could decrease the risk of thrombotic stroke.

Issue 89

SALONEN and co-workers, Research Institute of Public Health, University of Kuopio, Kuopio, Finland, and Department of Clinical Pharmacology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, jukka.salonen@uku.fi, conducted a randomized controlled trial of antioxidant supplementation in the prevention of atherosclerosis.
Background: The aim of the study was to examine the effects of vitamins C and E on the progression of carotid atherosclerosis, and to test the hypothesis that there would be a protective effect in men and in smokers, and that a synergism between the two vitamins could be shown.
Methods: This was a double-blinded two-by-two factorial trial with randomization in four strata (by gender and smoking status). 520 smoking and nonsmoking men and postmenopausal women aged between 45 and 69 years were divided into four groups receiving two daily doses of either 91 mg of vitamin E, 250 mg of vitamin C, both, or a placebo for three years. Atherosclerotic progression, defined as the linear regression slope of carotid artery mean intima-media thickness (IMT) as assessed by ultrasound, was calculated over 6-monthly assessments.
Results: The average increase of mean IMT was 0.020 mm per year in men randomized to placebo, 0.018 mm per year in the vitamin E group, 0.017 mm per year in the vitamin C group, and 0.011 mm per year in the group on both vitamins (p = 0.008 for combination vs placebo groups). The respective figures in women are 0.016, 0.015, 0.017, and 0.016 mm per year. The proportion of men with progressive thickening of the carotid artery was reduced by 74% (p = 0.003) by supplementation with both vitamins C and E as compared with placebo.
Conclusions: The study shows that a combined supplementation with reasonable doses of vitamins C and E can retard the progression of atherosclerosis in men. These results may imply benefits with regard to atherosclerosis-related diseases and mortality.
Salonen JT, Nyyssoenen K, Salonen R, Lakka HM, Kaikkonen J, Porkkala-Sarataho E, Voutilainen S, Lakka TA, Rissanen T, Leskinen L, Tuomainen TP, Valkonen VP, Ristonmaa U, Poulsen HE. Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis. Journal of Internal Medicine 248 (5): 377-386, Nov 2002.
Comments: This is a study of impressive scope with results that show the potential health benefits of multivitamin supplementation upon patients with atherosclerosis. What a pity that the EU Directive may lower the dosages available of nutrients such as vitamins C and E.

ASCHERIO, Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA, describes epidemiological studies on dietary fats and coronary heart disease.
Abstract: The results of large prospective epidemiological studies support the hypothesis that the risk of coronary heart disease depends on the quality rather than on the quantity of dietary fat. Saturated fatty acids and cholesterol increase the risk of coronary heart disease as predicted by their well-established effects on blood lipids. Strong evidence has emerged that the deleterious effects of trans unsaturated fatty acids go beyond those predicted by their influence on the ratio of low-density lipoprotein to high-density lipoprotein cholesterol. Increased consumption of the polyunsaturated fatty acids linoleic and linolenic acid appears to reduce the risk of coronary heart disease.
Ascherio A. Epidemiological studies on dietary fats and coronary heart disease. The American Journal of Medicine 13 Suppl 9B: 9S-12S, Dec 30, 2002.

LEMAITRE and colleagues, Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle 98101, USA, rozenl@u.washington.edu, have studied n-3 polyunsaturated fatty acids and myocardial infarction in older adults in the Cardiovascular Health Study.
Background: Little is known about the relation of dietary intake of n-3 polyunsaturated fatty acids, i.e. docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and alpha-linolenic acid, with ischaemic heart disease in older adults. This study aimed to investigate the association of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid with the risk of fatal ischaemic heart disease and nonfatal myocardial infarction in older adults.
Methods: This was a case-controlled study nested in the Cardiovascular Health Study, a cohort study of adults aged 65 and over. 54 cases of fatal myocardial infarction and other fatal ischaemic heart disease, and 125 cases of nonfatal myocardial infarction were matched to 179 randomly selected controls. Plasma phospholipid concentrations of n-3 polyunsaturated fatty acids were measured in blood samples drawn approximately 2 years before the event.
Results: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischaemic heart disease (odds ratio 0.32, p = 0.01). A tendency to lower risk, after adjustment for other risk factors, was observed for alpha-linolenic acid (odds ratio 0.52, p = 0.1). However n-3 polyunsaturated fatty acids were not associated with lower risk of nonfatal myocardial infarction.
Conclusions: Higher combined intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischaemic heart disease in older adults. The association of these n-3 polyunsaturated fatty acids with fatal but not with nonfatal myocardial infarction is consistent with possible antiarrhythmic effects of these fatty acids.
Lemaitre RN, King IB, Mozaffarian D, Kuller LH, Tracy RP, Siscovick DS. n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. The American Journal of Clinical Nutrition 77 (2): 279-280, Feb 2003.
Comments: These are important results which again suggest important roles for essential fatty acids including DHA and EPA.

Issue 87

FLEMING and colleagues, Mineral Bioavailability Laboratory, Jean Mayer US Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MA02111, USA, investigated dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort.
Background: High iron stores in the body may contribute to the risk of several chronic diseases. It is unknown whether dietary factors contribute to high iron stores.
Methods: The relation between diet (as assessed with a food frequency questionnaire) and the risk of high iron stores (serum ferritin levels greater than 300 and 200 micrograms per litre in men and women respectively) in 614 subjects aged between 68 and 93 years was evaluated.
Results: The risk of high iron stores was increased in a) subjects who took supplements containing 30 micrograms or more iron as compared to non-users; b) in subjects who ate more than 21 servings of fruit per week compared to those who consumed up to 14 servings of fruit per week; c) in subjects who consumed more than 4 servings of red meat per week compared to those who ate less than 4 servings of red meat per week. Whole-grain intake was inversely associated with the risk of high iron stores.
Conclusions: Among the elderly, intakes of highly bioavailable forms of iron (supplemental iron or red meat) and of fruit, a dietary source of vitamin C which enhances iron uptake, promote high iron stores. Foods containing phytate (whole grains) decrease these stores. Thus individual dietary patterns may be important modulators of high iron stores.
Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PWF, Wood RJ. Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort. The American Journal of Clinical Nutrition 76 (6): 1375-1384, Dec 2002.

GUALLER and co-workers, Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD 21205-2223, USA, egualler@jhsph.edu, studied mercury, fish oils, and the risk of myocardial infarction.
Background: It has been suggested that mercury increases the risk of cardiovascular disease. Because fish intake is a major source of mercury exposure, the mercury contamination of fish might counteract the beneficial effects of fish n-3 fatty acids.
Methods: In a case-control study conducted in 8 European countries and Israel, the joint association of mercury levels in toenail clippings and docosahexaenoic acid (DHA) levels in adipose tissue with the risk of first myocardial infarction in men was evaluated. The patients were 684 men with a first diagnosis of myocardial infarction, and the controls were 724 men selected to be representative of the same populations.
Results: After adjustment for DHA level and coronary risk factors, the mercury levels in patients were 15% higher than in control subjects. The odds ratio for myocardial infarction, after adjustment for risk factors, was 2.16 in the highest quintile of mercury compared to the lowest quintile. After adjustment for mercury, the DHA levels were found to be inversely associated with the risk of myocardial infarction.
Conclusions: Toenail mercury levels were directly associated with the risk of myocardial infarction, and the adipose-tissues DHA levels were inversely associated with the same risk. High mercury content may diminish the cardio-protective effect of fish intake.
Gualler E, Sanz-Gallardo MI, van-t-Veer P, Bode P, Aro A, Gomez-Aracena J, Kerk JD, Riemersma RA, Martin-Moreno JM, Kok FJ. Mercury, fish oils, and the risk of myocardial infarction. The New England Journal of Medicine 347 (22): 1747-1754, Nov 2002.

YOSHIZAWA and colleagues, Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA, explored the connections between mercury and the risk of coronary heart disease in men.
Background: A high dietary intake of the metal mercury from the consumption of fish has been thought to increase the risk of heart disease.
Methods: In a nested case-control design, the association between mercury levels in toenail clippings and the risk of coronary heart disease was investigated in male health professionals with no previous history of heart disease or cancer. Toenail clippings were collected in 1987 from 33,737 cohort members. During the next five years, 470 cases of coronary heart disease were documented. Each patient was matched according to age and smoking habit with a randomly selected control subject.
Results: The mercury levels in these men were significantly correlated with fish consumption (p = 0.001). Also the mean mercury levels were higher in dentists than in non-dentists. However the mercury levels were not significantly associated with coronary heart disease.
Conclusions: These findings do not support the assumption that increased mercury levels increase the risk of coronary heart disease, although a weak relation cannot be ruled out.
Yoshizawa K, Rimm EB, Morris JS, Spate VL, Hsieh CC, Spiegelman D, Stampfer MJ, Willett WC. Mercury and the risk of coronary heart disease. The New England Journal of Medicine 347 (22): 1755-1760, Nov 2002.

Comment: The above two studies, one emanating from Johns Hopkins, the other from Harvard, come to the exact opposite conclusion regarding the association of mercury with increased risk of heart attack. How interesting! Such is the nature of research.

Issue 86

ULRICH-MERZENICH and co-workers, Medizinixche Poliklinik, University of Bonn, Germany, Gudrun.Ulrich-Merzenich@uni-bonn.de, have discovered that vitamin C and vitamin E modulate human vascular endothelial and smooth muscle cell proliferation.

Background: Vitamins C and E are thought to play a role in atherosclerosis. In order to investigate this further, their effects, and the effect of varying concentrations of the oxidised form of Low Densitiy Lipoprotein (LDL) (which acted to simulate an atherosclerosis- promoting agent) on arterial endothelial cells and smooth muscle cells (both cell types that make up the walls of arteries) in culture were investigated.

Methods: Cells in culture were incubated with ‘preventive’ concentrations of vitamins C and E or both together. Cell proliferation and DNA synthesis were then measured.

Results: Vitamin C alone or in combination with vitamin E increased significantly cell proliferation and DNA synthesis in endothelial cells but decreased both in smooth muscle cells. It was found that the oxidised form of LDL promotes the proliferation of smooth muscle cells but decreases the growth of endothelial cells. Its effects could be partly reversed by high concentrations of antioxidant vitamins.

Conclusions: Vitamins C and E may act to prevent atherosclerosis in two steps: first by stimulating regrowth of the endothelium, and second by inhibiting smooth muscle cell growth.

Ulrich-Merzenich G, Metzner C, Schiermeyer B, Vetter H, et al. Vitamin C and E antagonistically modulate human vascular endothelial and smooth muscle cell DNA synthesis and proliferation. European Journal of Nutrition 41 (1): 27-34, Feb 2002.

Comment: Again, a clinically significant result that ought to result in the prescription of vitamins C and E within the treatment protocols of heart attack patients.

Issue 84

DAMODARAN and co-workers, Bhabha Atomic Research Centre, Medical Division Mumbai, assess the therapeutic potential of Yoga in modifying cardiovascular risk.

Background: The effect of Yoga on the physiological and psychological wellbeing, and on psychomotor parameters and cardiovascular risk factors was investigated in mildly to moderately hypertensive patients.

Methods: 20 patients aged 35-55 with mild to moderate essential hypertension underwent daily Yoga practice for one hour for a period of three months. Variables measured before and after this period included blood glucose, lipid profile, catecholamines, MDA, vitamin C, cholinesterase, urinary VMA, Personal Orientation Inventory, and subjective wellbeing.

Results: The investigators found a decrease in blood pressure and in drug scores modifying risk factors. There was an improvement in overall wellbeing and quality of life. The decrease measured in VMA, catecholamines, and MDA, suggesting a decrease in sympathetic activity and oxidative stress.

Conclusion: Yoga can positively modify the risk of cardiovascular disease in mild to moderate hypertension.

Damodaran A, Malathi A, Patil N, Shah N, Suryavansihi, Marathe S. Therapeutic potential of Yoga practices in modifying cardiovascular risk profile in middle aged men and women. The Journal of the Association of Physicians of India 50 (5): 633-640, May 2002.

RIVERA and colleagues, Departamento de Ultra-estrutura e Biologia Celular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil, show that progressive Chagas’ cardiomyopathy is associated with low selenium levels.

Background: Selenium deficiency is linked to some cardiomyopathies.

Methods: Cross-sectional study involving 170 patients from the same geographical region, divided into 4 groups according to clinical criteria: Indeterminate or asymptomatic (IND), cardiac asymptomatic (CARDa), cardiac symptomatic with moderate to severe heart dysfunction (CARDb), healthy adults (HA). Various biochemical parameters were measured.

Results: Selenium was significantly lower in CARDb patients than in either CARDa, IND, or HA subjects. This was not associated with a decrease in activity of glutathione peroxidase, or with a change in thyrotropin levels. Selenium correlated positively and significantly with ventricular ejection fraction.

Conclusions: The decrease in selenium seems to be a biological marker for Trypanosoma cruzi infection and related to the progression of the pathology.

Rivera MT, de Souza AP, Moreno AHM, Xavier Ss, Gomes JAS, Rocha MOC, Correa OR, Neve J, Vanderpas J, Araujo JTC. Progressive Chagas’ cardiomyopathy is associated with low selenium levels. The American Journal of Tropical Medicine and Hygiene 66 (6): 706-712, Jun 2002.

Issue 83

HALPIN et al., Inova Heart Center, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA, E: linda.halpin@inova.com, explored the use of guided imagery in heart surgery.

Background: Clinical research has shown that guided imagery can reduce preoperative anxiety and postoperative pain in patients undergoing surgical procedures.

Methods: Controlled study to compare surgical outcomes in patients undergoing cardiac surgery with or without a guided imagery programme. Data from the hospital’s financial database and patient satisfaction data were analyzed. A questionnaire was developed to assess the benefits of the guided imagery programme.

Results: Patients who completed the guided imagery programme had a shorter average length of stay, a decrease in average direct pharmacy costs, and a decrease in average direct pain medication costs, while maintaining high overall patient satisfaction.

Conclusions: Guided imagery is now considered a complementary means to reduce anxiety, pain, and length of stay amongst the hospital’s cardiac surgery patients.

Issue 82

NOGUCHI and colleagues, Graduate School of Human and Environmental Studies, Kyoto University, Japan, noguchi@brain.riken.go.jp, explored the possible preventive effects of sesamin (a constituent of sesame oil) and vitamin E against high blood pressure and thrombosis in rats.

Methods: Effects of the nutrients were investigated in 5-week-old, stroke-prone, spontaneously hypertensive rats (SHRSP). In a randomized, controlled study, the animals received, for 5 weeks, 1) a normal diet; 2) a diet containing 1000 mg/kg vitamin E (alpha-tocopherol); 3) a diet containing 1000 mg/kg sesamin; or 4) a diet containing 1000 mg vitamin E plus 1000 mg sesamin per kg. Resting blood pressure was measured once a week and thrombotic tendency (number of laser pulses required for the formation of an occlusive thrombus) at the end of 10 weeks. 8-hydroxy-2’-deoxyguanosine (8-OHdG) in urine, an indicator of oxidative stress, was also measured.

Results: Systolic blood pressure and urinary 8-OHdG levels increased significantly with age in control rats, while these effects were significantly suppressed in rats in the other three groups. After 10 weeks, the tendency for thrombosis was significantly higher in the control group compared with the other three groups (p<0.05).

Conclusion: Daily supplementation with vitamin E and sesamin for 5 weeks reduced age-related elevations in blood pressure, oxidative stress and thrombotic tendency in stroke-prone spontaneously hypertensive rats. Similar supplementations in humans may help prevent the occurrence of high blood pressure and stroke.

Issue 81

MARESTA and colleagues, Department of Cardiology, Ospedale S. Maria della Croci, Ravenna, Italy, carried out a study to investigate whether long-term supplementation with omega-3 fatty acids (FA) prior to undergoing percutaneous transluminal coronary angioplasty (PTCA) might reduce the occurrence of restenosis (reblockage of coronary arteries) in the future.
Background: Some previous studies have examined whether supplementation with omega-3 FAs can reduce restenosis, but the results have been inconclusive.
Methods: This randomized, double-blind, placebo-controlled trial enrolled 339 patients scheduled to undergo PTCA for coronary artery disease. Subjects received either: 1) 6 x 1-g capsules daily comprising 3 g eicosapentaenoic acid (EPA) and 2.1 g docosahexaenoic acid (DHA); or 2) identical capsules containing olive oil (‘placebo’). Treatment was begun 1 month prior to PTCA and continued for 1 further month after the procedure. Of the original 339 patients randomized to study treatments, 257 patients (125 in the omega-3 FA group and 132 in the placebo group) who were well matched for risk factors underwent successful balloon-only PTCA (280 total lesions) and were able to undergo evaluation at 6 months by repeat angiography. Restenosis was defined as recurrence of greater than 50% diameter blockage of the dilated artery (Definition I) and as greater than 50% loss of the short-term gain immediately after PTCA (Definition II).
Results: In the omega-3 FA group, restenosis rates were 29.4% versus 39.6% in the placebo group according to Definition I; analogous restenosis rates according to Definition II were 31.6% and 35.4% respectively (no significant difference). Restenosis rates per patient were 31.2% in the omega-3 FA group versus 40.9% in the placebo group according to Definition I; and were 33.6% and 37.1% respectively according to Definition II (no significant difference).
Conclusion: 1-months’ supplementation with omega-3 FAs (EPA and DHA) prior to PTCA resulted in a small (up to 10%) but statistically significant decrease in the rate of occurrence of restenosis compared with placebo treatment.
Maresta A et al. Prevention of postcoronary angioplasty restenosis by omega-3 fatty acids: main results of the Esapent for Prevention of Restenosis ITalian Study (ESPRIT). American Heart Journal 143 (6): E5. Jun 2002.

ANGERER and colleagues, Klinikum der Universität München, Institut und Poliklinik für Arbeits- und Umweltmedizin-Innenstadt, Ziemssenstrasse 1, Germany, peter.angerer@arbeits.med.uni-muenchen.de, investigated the effects of 2 years of daily dietary supplementation with omega-3 polyunsaturated fatty acids (PUFAs) extracted from fish oil on the progression of atherosclerosis in the carotid artery in patients with coronary heart disease.
Background: The investigators carried out a randomized, double-blind, placebo-controlled clinical trial that examined the long-term effects of supplementation with omega-3 PUFAs on the progression of coronary atherosclerosis. As a sub-study within this trial, effects on carotid artery atherosclerosis progression were also investigated.
Methods: Subjects were 223 patients with coronary artery disease. 2 years’ dietary supplementation with 1.65 g omega-3 PUFAs daily was compared with placebo treatment. The patients underwent a comprehensive clinical examination, coronary angiography and B-mode ultrasound examination of the carotid arteries (to measure intima media thickness) at the beginning and end of the study. The global change in carotid atherosclerosis was evaluated visually by an expert panel on a semi-quantitative scale. Change in overall mean maximum intima media thickness was also measured.
Results: 171 patients completed the study. 38% of patients in the fish-oil group, compared with 35% in the placebo group, showed progression according to the global change score (no significant difference). The fish-oil group showed an increase in mean (SD) maximum intima media thickness of 0.070.13 mm, compared with an increase of 0.050.11 in the placebo group, (no significant difference). Changes in carotid arteries did not show any association with changes in coronary arteries.
Conclusion: Supplementation for 2 years with daily omega-3 PUFAs did not result in any slowing of the progression of atherosclerosis in carotid arteries measured by ultrasound in this group of selected patients with coronary artery disease.
Angerer P et al. Effect of dietary supplementation with omega-3 fatty acids on progression of atherosclerosis in carotid arteries. Cardiovascular Research 54 (1): 183-90. Apr 2002.

Issue 80

FIELDS and colleagues, Center for Natural Medicine and Prevention, College of Maharishi Vedic Medicine, Maharishi University of Management, Fairfield, Iowa 52557, USA, investigated the effect of reducing simultaneously several known or suspected risk factors for coronary heart disease (CHD) in healthy elderly people, using a combination treatment approach taken from Maharishi Vedic Medicine (MVM).
Background: CHD is associated with a range of risk factors, many of which have been investigated individually, but few in combination, in clinical studies.
Methods: In this pilot study, the researchers compared a combination treatment involving modification of diet, exercise, herbal food supplementation and stress reduction, taken from the MVM traditional system of natural medicine, with two control treatments: ‘modern medicine’ (conventional recommendations for diet, exercise and multivitamin supplementation) and ‘usual care’ (no treatment). Subjects were 57 elderly individuals (mean age 74 years). Carotid intima media thickness (IMT), a measure of peripheral atherosclerosis and an indicator of coronary atherosclerosis, was measured by B-mode ultrasound before and 1 year after treatment.
Results: 46 of the subjects completed the study. A larger proportion of MVM subjects (16/20) showed decreased IMT compared with the combined findings from the two control groups (12/23; odds ratio [OR] 3.7) (5/9 in the ‘modern medicine’ group and 7/14 in the ‘usual care’ group). Among subjects who had several risk factors for CHD (‘high-risk’ subjects), those in the MVM group showed a greater decrease in IMT (-0.32±0.23 mm, mean±SD) than those in the ‘modern medicine’ (-0.082±0.095) or ‘usual care’ (+0.022±0.085) groups. For all MVM subjects as well as for all high-risk MVM subjects, within-group IMT reductions were statistically significant (-0.15±0.21; all MVM, n=20; high-risk MVM, n=6).
Conclusion: The results of this pilot study indicate that this multi-modality approach, taken from traditional MVM, can reduce atherosclerosis in elderly subjects, particularly in those at high risk of CHD.
Fields JZ et al. Effect of a multimodality natural medicine program on carotid atherosclerosis in older subjects: a pilot trial of Maharishi Vedic Medicine. The American Journal of Cardiology 89 (8): 952-8. Apr 2002.

MARCHIOLI and colleagues, Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy, E: marchioli@negrisud.it, assessed the time course of the effect of n-3 polyunsaturated fatty acids (PUFAs) in reducing death rates in patients surviving a recent heart attack (myocardial infarction, MI).
Methods: The investigators analysed data obtained in an Italian clinical trial (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico Prevenzione [GISSI]), in which 11,323 patients surviving a recent (3 months) MI received 1) supplements of n-3 PUFAs (1 g/day); 2) supplements of vitamin E (300 mg/day); 3) supplements of both PUFAs and vitamin E; or 4) no treatment (control), in addition to optimal drug treatment and lifestyle advice. Data were analysed for early efficacy of n-3 PUFA treatment with regard to total, cardiovascular (CV), cardiac, coronary and sudden death; non-fatal MI; total coronary heart disease (CHD); and cerebrovascular (CBV) events.
Results: n-3 PUFA treatment significantly lowered total mortality (relative risk [RR] 0.59) from as early as 3 months of treatment and the risk of sudden death (RR 0.47) from 4 months. Similarly significant reductions in CV, cardiac and coronary deaths were seen starting at 6 to 8 months of treatment.
Conclusion: Low-dose n-3 PUFA supplementation had early beneficial effects on total mortality and sudden death, supporting suggestions that n-3 PUFAs may have antiarrhythmic activity. Such a mechanism is consistent with results of studies on isolated heart cells and those from animal, clinical and epidemiological studies.
Marchioli R et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation 105 (16): 1897-903. Apr 2002.

Comment: These results appear to offer significant hope for heart attack victims.

Issue 79

MCKECHNIE and colleagues, Department of Internal Medicine, Division of Cardiology, University of Michigan Medical Center, Ann Arbor, MI, USA, investigated possible associations of antioxidant supplementation with changes in endothelial function and changes in oxidation of low-density lipoprotein cholesterol (LDLC) in patients with coronary artery disease (CAD).
Background: In population studies, intakes of antioxidants have been found to correlate with CAD. However, formal clinical trials have produced inconsistent findings.
Methods: This was a double-blind, randomized, placebo-controlled, 12-week trial. 18 patients (mean age 62.4 years) with established CAD received one of three study treatments daily: 1) 400 IU vitamin E, 500 mg vitamin C + 12 mg beta-carotene; 2) 800 IU vitamin E, 1000 mg vitamin C + 24 mg beta-carotene; or 3) placebo. Smokers and patients with diabetes were excluded from the study. Changes (percent and absolute) in brachial artery diameter in response to reactive hyperaemia induced by occlusion release were measured for assessment of endothelial function. Measures of low-density lipoprotein (LDL) oxidation (lag phase), endothelial function, dietary composition, serum antioxidants and lipids were recorded at baseline and 12 weeks.
Results: There were significant differences in the changes in plasma levels of alpha-tocopherol, vitamin C and beta-carotene between the placebo and the antioxidant-supplemented groups at 12 weeks. Although all three groups of patients showed significant improvements in lag phase from baseline, the change was greater in antioxidant-supplemented compared with placebo-treated patients; however, this difference was not statistically significant. Antioxidant-supplemented patients showed a slight but statistically non-significant improvement in brachial reactivity from baseline to 12 weeks, whereas a significant improvement in this measure was observed in the placebo group. Change in lag phase appeared to be unrelated to change in endothelial function. After adjusting for confounding factors, the investigators found that antioxidant supplementation was not a significant predictor of brachial reactivity.
Conclusion: Dietary supplementation with antioxidants caused no significant changes in brachial artery reactivity, although it did significantly increase plasma antioxidant concentrations and improve lag phase. Larger-scale trials are needed to confirm the present findings. Further studies should also evaluate effects of dietary supplementation with individual antioxidants.
McKechnie R et al. Antioxidant nutrient supplementation and brachial reactivity in patients with coronary artery disease. The Journal of Laboratory and Clinical Medicine 139 (3): 133-9. Mar 2002.

FANG and colleagues, Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA 02115, USA, jfang@partners.org, investigated whether dietary supplementation with antioxidant vitamins (C and E) might slow the progression of cardiac transplant-associated arteriosclerosis.
Background: Oxidative stress occurs during cardiac transplantation and may contribute to the progression of coronary atherosclerosis.
Methods: This was a double-blind, randomized, placebo-controlled, prospective clinical trial carried out in 40 patients at zero to 2 years after cardiac transplantation. Patients received 1) 500 mg vitamin C + 400 IU vitamin E twice daily (n=19) or 2) placebo (n=21) for 12 months. All patients also received the cholesterol-lowering drug pravastatin. Patients were assessed at baseline and 12 months for: change in average intimal index (plaque area divided by vessel area), measured by intravascular ultrasonography (IVUS); coronary endothelium-dependent vasoreactivity, assessed by intracoronary infusion of acetylcholine; and plasma levels of vitamins C and E. Results were analysed on an intent-to-treat basis.
Results: In the vitamin-supplemented group, plasma levels of vitamins C and E increased significantly from baseline to 12 months, whereas plasma vitamin levels remained unchanged in the placebo group. In the vitamin-supplemented group, the intimal index did not change significantly from baseline to 12 months; however, this index increased by 82% in the placebo group. No changes in measures of coronary endothelial function were observed in either treatment group.
Conclusion: The findings indicate that dietary supplementation with antioxidant vitamins (C and E) can slow early progression of arteriosclerosis associated with cardiac transplantation.
Fang JC et al. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet 359 (9312): 1108-13. Mar 2002.

HU and colleagues, Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA, Frank.hu@channing.harvard.edu, examined the possible link between dietary fish and long-chain omega-3 fatty acid consumption and risk of coronary heart disease (CHD) in women.
Background: In men, studies have shown that a diet high in fish and omega-3 fatty acids is associated with a lower risk of CHD. Few such data are available with regard to women.
Methods: Subjects were 84,688 female nurses enrolled in the Nurses’ Health Study. Ages ranged from 34 to 59 years. At baseline (in 1980), no subjects had detectable cardiovascular disease or cancer. Subjects completed validated questionnaires, which covered dietary constituents and other data, in 1980, 1986, 1990 and 1994. The main outcome measures investigated were the incidence of non-fatal myocardial infarction (MI) and deaths due to CHD.
Results: During the follow-up period, 1513 incident cases of CHD were recorded (1029 cases of non-fatal MI and 484 cases of CHD deaths). Women who consumed higher levels of fish (more than once per month) had a lower risk of CHD. After data were adjusted for age, smoking and other cardiovascular risk factors, the relative risks (RRs) of CHD were as follows: 1) for women who consumed fish 1 to 3 times a month, 0.79; for women who consumed fish once a week, 0.71; for women who consumed fish 2 to 4 times a week, 0.69; for women who consumed fish 5 or more times a week, 0.66. Women who consumed higher levels of omega-3 fatty acids also had a lower risk of CHD. RRs of CHD across quintiles of intake (low to high) were 1.0, 0.93, 0.78, 0.68 and 0.67 respectively. The decreased risk with increased consumption of fish and omega-3 fatty acids appeared to be stronger for CHD-related deaths than for non-fatal MI (RR for fish consumption 5 times a week, 0.55 for CHD deaths and 0.73 for non-fatal MI.
Conclusion: As has been found previously for men, higher dietary levels of fish and omega-3 fatty acids are linked to a lower risk of CHD, particularly CHD-associated deaths, in women.
Hu FB et al. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. Journal of the American Medical Association 287 (14): 1815-21. Apr 2002.

Comment: The above research demonstrates the significant effects upon various measures of heart disease which can be modulated by antioxidant, essential fatty acid supplementation and fish consumption.

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