Search

The evidence from formal, controlled, long-term clinical trials that changes in dietary fats reduce the incidence of ischemic (coronary) heart disease (IHD) is unimpressive. Mostly these trials were underpowered and in several the rigor of dietary control in the intervention and control groups was inadequate. Six controlled clinical trials in healthy people of diets low in saturated fat and cholesterol, also accompanied by changes in other risk factors, were unsuccessful in reducing the incidence of IHD. An exception was the Oslo trial in which concurrent cigarette smoking was almost halved. Similarly, in the only two clinical trials of the secondary prevention of IHD through use of diets low in saturated fats and cholesterol there was no significant effect on IHD recurrence rate. This may relate to poor compliance outside strict clinic conditions. In contrast, five of six secondary prevention trials in which diets low in saturated fats were supplemented with polyunsaturated fats reduced IHD deaths and, to a lesser extent, all-cause mortality. No formal trial has been reported of the effects on IHD of diets high in monounsaturated fats. The greatest benefit for patients with IHD has come from diets supplemented with n-3 fatty acids (two trials), and this benefit was independent of changes in plasma lipoproteins. The evidence from these clinical trials indicates that more emphasis should be given in national and international dietary recommendations to supplementation with polyunsaturated fats, particularly foods rich in n-3 fatty acids, than to diets low in total and saturated fats.

How long-term dietary intake of essential fatty acids affects the fatty-acid content of aortic plaques is not clear. We compared the fatty-acid composition of aortic plaques with that of post-mortem serum and adipose tissue, in which essential fatty-acid content reflects dietary intake. Positive associations were found between serum and plaque omega 6 (r = 0.75) and omega 3 (r = 0.93) polyunsaturated fatty acids, and monounsaturates (r = 0.70), and also between adipose tissue and plaque omega 6 polyunsaturated fatty acids (r = 0.89). No associations were found with saturated fatty acids. These findings imply a direct influence of dietary polyunsaturated fatty acids on aortic plaque formation and suggest that current trends favouring increased intake of polyunsaturated fatty acids should be reconsidered.

Evidence for the utilisation of substrates by the ischaemic myocardium and its dependence for viability on a critical supply of glucose was established many years ago. It was recognised that an excess of free fatty acids (FFA) could increase the severity of ischaemic damage and possibly be arrhythmogenic. But metabolic intervention to improve survival during acute myocardial infarction was not regarded as a priority, perhaps because of uncertainty about its value and the advent of trials of beta-blocker and antiarrhythmic drugs. There has never been an adequate trial of the benefit to the ischaemic or infarcting myocardium of increasing local glucose concentrations or reducing the availability of FFA. We have taken into account new knowledge of the effects of fatty acids on cation channels and brought up to date the arguments for metabolic intervention with glucose-insulin solutions or antilipolytic drugs sustained ischaemia.

The insulin response to a standard oral glucose tolerance test (OGTT) and other anthropometric and biochemical risk factors for coronary heart disease (CHD) were measured in a random sample of 107 Edinburgh men, who were initially studied in 1976 when they were 40 and who were reexamined in 1988-89. Fasting glucose and glucose response to OGTT were higher in 1988-89 than in 1976. In contrast, insulin levels did not differ between the initial and follow-up study either before or after the glucose load. Body mass indices increased, except triceps skinfold. Changing patterns in both fasting and OGTT insulin or glucose levels in individuals were related to changes in bodyweight or in subscapular skinfolds. Modifications in serum total and HDL cholesterol were related to changes in fasting insulin and insulin area, respectively, but not to glucose data. Eleven men developed clinical CHD. Neither glucose nor insulin measures obtained in 1976 differed between those with and without CHD. Weight-height index and abdominal skin-folds were higher in those with CHD. HDL cholesterol was significantly lower (P less than 0.05). Abdominal skin-fold but not body mass index remained significant when adjusted for HDL cholesterol. This small study confirms the importance of central obesity and low HDL cholesterol but failed to identify insulin as a risk factor for CHD in this Scottish population.

The relation between risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene was examined in a population case-control study of 110 cases of angina, identified by the Chest Pain Questionnaire, and 394 controls selected from a sample of 6000 men aged 35-54. Plasma concentrations of vitamins C and E and carotene were significantly inversely related to the risk of angina. There was no significant relation with vitamin A. Smoking was a confounding factor. The inverse relation between angina and low plasma carotene disappeared and that with plasma vitamin C was substantially reduced after adjustment for smoking. Vitamin E remained independently and inversely related to the risk of angina after adjustment for age, smoking habit, blood pressure, lipids, and relative weight. The adjusted odds ratio for angina between the lowest and highest quintiles of vitamin E concentrations was 2.68 (95% confidence interval 1.07-6.70; p = 0.02). These findings suggest that some populations with a high incidence of coronary heart disease may benefit from eating diets rich in natural antioxidants, particularly vitamin E.

Low levels of essential polyunsaturated fatty acids of the n-6 series are associated with coronary heart disease. Linoleic acid, but not gamma-linolenic acid requires the activity of delta 6-desaturase for its conversion to dihomo-gamma-linolenic and arachidonic acid. Evening primrose oil (EPO) and safflower oil (SO) are rich in linoleic acid, but EPO contains also 9% gamma-linolenic acid. The effect of EPO (10, 20 and 30 ml/day) and SO (20 ml/day) for 4 months on the deposition of linoleic acid metabolites in adipose tissue of 4 groups of 6-9 men with low adipose dihomo-gamma-linolenic acid was examined. EPO but not SO increased adipose dihomo-gamma-linolenic acid level from 0.080 +/- 0.005% to 0.101 +/- 0.005% (P less than 0.01; 20 ml/day for 4 months). Adipose dihomo-gamma-linolenic/linoleic acid ratio increased with EPO from 0.99 +/- 0.16 X 10(2) to 1.13 +/- 0.14 X 10(2) and fell on SO from 1.04 +/- 0.10 X 10(2) to 0.90 +/- 0.07 X 10(2) (P less than 0.01). Similar qualitative changes in the relative amount of dihomo-gamma-linolenic acid in serum triglyceride and cholesteryl ester fractions were observed. At the dose of 20 ml/day, SO and EPO did not differ in their effect on serum cholesterol (7.13 +/- 0.43 vs. 7.33 +/- 0.42 mmol/l (NS)), LDL-cholesterol (5.10 +/- 0.32 vs. 4.88 +/- 0.46 mmol/l (NS)) nor did the 2 oils differ in their effect on HDL-cholesterol. These results suggest that linoleic acid is not readily converted to dihomo-gamma-linolenic acid due to a low activity of delta 6-desaturase in these highly selected men. EPO was not an effective hypocholesterolaemic agent in this study.

The relation between coronary heart disease (CHD) and fatty acid composition of adipose tissue and platelets was examined in a random sample of 448 middle-aged Scottish men. The linoleic acid (18:2n6) content in adipose tissue of 28 men with previously unidentified CHD was significantly lower than that in the rest of the group. Platelet linoleic and other fatty acids were not significantly different in men with new CHD. Fatty acid content of adipose tissue reflects long-term dietary intake, and a 7-day weighed dietary record in a random sub-sample of 164 men confirmed that intake of linoleic acid in 10 of the 28 new CHD cases was significantly lower than in the healthy men. In a multiple logistic analysis adipose tissue linoleic acid, age, high density lipoprotein cholesterol, and weight/height index each made an independent contribution to the explanation of new CHD. When all fatty acids were included in a second regression analysis, low concentrations of dihomo-gamma-linolenic (20:3n6) acid in adipose tissue showed a more significant relation with new CHD than did linoleic acid.

The effects of sulphinpyrazone on heart-rate and blood-pressure responses to exercise were assessed in 15 normal volunteers by a randomised double-blind crossover technique. Submaximal exercise tests were performed 1 and 2 hours after either sulphinpyrazone (SPZ) 200 mg orally or placebo. Heart-rate and blood-pressure responses were unchanged at rest and during exercise 1 hour after SPZ but after 2 hours there was a significant fall in the product of heart-rate and blood-pressure during exercise (peak 35.8 +/- 1.5 x 10(-3) mmHg beats/min, placebo: 33.0 +/- 1.3 x 10(-3) sulphinpyrazone, p < 0.005) and for the first 2 minutes of recovery. This was mainly due to a decreased exercise-induced rise in systolic blood-pressure with lesser effects on heart-rate. This haemodynamic effect of SPZ has a potentially protective oxygen-sparing effect on the normal myocardium during exercise and may explain its apparent benefit in reducing sudden cardiac death after myocardial infarction.

The effect of lowering raised plasma-free-fatty acids (F.F.A.) on the incidence of serious ventricular arrhythmias after myocardial infarction was assessed by a double-blind trial in eighty-one patients. A nicotinic-acid analogue (N.A.A.) with very slight haemodynamic effects was given within 12 hours of the onset of myocardial infarction to lower plasma-F.F.A. When treatment with N.A.A. was started within 5 hours of the onset of symptoms, the numbers of patients with ventricular symptoms, the numbers of patients with ventricular tachycardia were significantly reduced, provided elevated plasma-F.F.A. levels were rapidly lowered and maintained in the normal range throughout the treatment period. The incidence of R-on-apex T ventricular premature beats and beats in which the ectopic R wave interrupted the apex of the T wave of a previous ventricular premature beat was also reduced in patients receiving N.A.A within 5 hours of the onset of symptoms. Plasma-total-catecholamines and serum-creatine-kinase levels were similar in the N.A.A.-treated and placebo groups. N.A.A. rarely caused skin flushing, but vomiting occurred in some patients after many hours of treatment. These findings suggest that treatment directed towards stabilsing the matabolism of the ischaemic myocardium can be of therapeutic value and lead to fewer serious ventricular arrhythmias.

The relation between alcohol consumption and dietary intake was examined in 164 middle-aged Scottish men taking part in a study of risk factors for coronary heart disease (CHD). A 7-d weighed dietary record was used to assess alcohol and nutrient intake. The mean daily intake of alcohol was 26 g (SD 31 g). Energy derived from alcohol tended to replace energy derived from other nutrients and increasing intake of alcohol was associated with a decrease in the amounts of carbohydrate, total fat, and saturated and monounsaturated fatty acids in the diet. Those with a low alcohol intake (0.1-9 g alcohol/d) had a higher intake of total fiber, cereal fiber, polyunsaturated fatty acids, and linoleic acid and a smaller proportion smoked cigarettes. The differences are small but may contribute to the lower mortality from CHD reported by other studies in those with a low alcohol intake.

The effect of pindolol (a beta-blocker with intrinsic sympathomimetic activity, ISA) on fasting plasma lipid profile in 30 hypertensive patients was compared with atenolol (without ISA) in a crossover single blind study. Both drugs lowered blood pressure. HDL-cholesterol increased significantly with pindolol (from 1.15 +/- 0.05 to 1.34 +/- 0.05 mmol/l at 12 weeks, P less than 0.001), but not with atenolol. VLDL-cholesterol increased with atenolol (from 0.57 +/- 0.09 to 0.86 +/- 0.14 mmol/l at 12 weeks, P less than 0.002), while there was no change with pindolol. These changes in lipoprotein profile suggest a more favourable effect of pindolol than of atenolol on lipid profile.

The effect of dietary supplementation with 20 capsules/day Maxepa or olive oil on serum lipids has been studied in 21 hypercholesterolaemic patients using a double-blind crossover design. Platelet membrane eicosapentaenoic acid percentage rose by more than 10-fold after 2 months dietary supplementation with Maxepa. Total serum cholesterol was unchanged and there was a rise in LDL-cholesterol and HDL-cholesterol concentration in men, but no change in LDL-cholesterol, and a fall in HDL-cholesterol in women. In men and women there was a marked fall in total serum triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. Thus, Maxepa is not an effective treatment for isolated hypercholesterolaemia.

The relation between the fatty-acid composition of adipose tissue and platelet membranes and the estimated relative risk of coronary heart disease (CHD) was examined in a case-control study of new angina pectoris (AP) and first acute myocardial infarction (AMI). There were progressive inverse relations between adipose linoleic acid and platelet-membrane eicosapentaenoic acid and the estimated relative risk of AP. These relations were statistically independent of each other and traditional CHD risk factors. For AMI there was a progressive inverse relation between adipose linoleic acid and the estimated relative risk, but it was confounded by smoking habit. Smokers consume less linoleic acid than non-smokers. Although eicosapentaenoic acid in platelet membranes was lower in AMI patients than in controls, this difference was not significant. The estimated proportionate increase in risk of AP, independent of other CHD risk factors, was 1.2 (1.1-1.3) for a 1% decrease in linoleic acid or a 0.1% decrease in eicosapentaenoic acid.

A new technique has been used in dogs to make combined measurements in vivo of conduction delay, action potentials, and epicardial ST-segment during myocardial ischaemia. These measurements should provide new information about ionic and metabolic cellular changes relating to the onset of ventricular arrhythmias.