Etiology Of Ischemic Heart Disease Research Articles

High density lipoprotein cholesterol is not a major risk factor for ischaemic heart disease in British men.

The concentration of high density lipoprotein cholesterol (HDL cholesterol) in serum was measured at initial examination in a large prospective study of men aged 40-59 drawn from general practices in 24 British towns. After an average follow up of 4.2 years 193 cases of major ischaemic heart disease had been registered in 7415 men in whom both HDL cholesterol and total cholesterol values had been measured. The mean HDL cholesterol concentration was lower in the men with ischaemic heart disease ("cases") compared with other men, but the difference became small and non-significant after adjustment for age, body mass index, blood pressure, cigarette smoking, and concentration of non-HDL cholesterol. The higher mean concentration of non-HDL cholesterol in "cases" remained highly significant after adjustment for other factors. Men in the highest fifth of non-HDL cholesterol values had over three times the risk of major ischaemic heart disease compared with men in the lowest fifth. Multivariate analysis showed that non-HDL cholesterol was a more powerful predictor of risk than the HDL to total cholesterol ratio. These British findings were compared with six other prospective studies. All the larger studies showed similar results, suggesting that HDL cholesterol is not a major risk factor in the aetiology of ischaemic heart disease.

Ischaemic heart disease. An epidemiological perspective with special reference to electrolytes.

Ischaemic heart disease (IHD) is a major public health problem in most industrialised countries. In the death rates from IHD, marked differences exist between various countries and also between different areas of individual countries. Unfavourable dietary factors appear to play an important role in the aetiology of IHD, and thus differences in dietary habits and the quality of food may be mainly responsible for the geographic differences in the prevalence of IHD. The present liberal use of salt as well as the refining and other industrial processing of food increase the content of sodium and decrease the content of potassium and magnesium in the diet. The high intake of sodium and the inadequately low levels of potassium and magnesium in the diet predispose to the development of arterial hypertension. Since arterial hypertension is a major risk factor of IHD, the distorted electrolyte composition of our present diet can be considered an important aetiological factor of this disease. To decrease the body burden of sodium, diuretic agents are frequently used. Unfortunately, in the presence of the relatively low content of potassium and magnesium in the diet, the diuretic-induced increases in the excretion of these electrolytes commonly decrease the potassium and magnesium levels in the body. The falls in potassium and magnesium may increase the death rate from IHD by predisposing the heart to fatal arrhythmias, and also by other mechanisms. The likelihood of magnesium deficiency also appears to be influenced by the area of residence. The higher-than-average death rates from IHD in the so-called North Karelia area in eastern Finland and in some other areas with exceptionally high death rates from this disease may be at least partly due to the very low levels of magnesium in the soil and drinking water. It can be concluded that electrolyte disturbances have important implications in the aetiology and pathogenesis of IHD.

Copper and ischemic heart disease

Absolute or relative deficiency of copper is hypothesized to be of prime importance in the etiology of ischemic heart disease. According to recent estimates, only 25% of the diets in the United States contain the 2 mg of copper thought to be required daily by adults. Some of these diets have ratios of zinc to copper greater than those that have produced hypercholesteremia in animals. There are many epidemiologic associations between the ratio of zinc to copper and dietary characteristics, organ analyses, clinical status, and environmental features that relate the metabolism of these elements to the anatomy, chemistry, pathology, pharmacology, and physiology of ischemic heart disease. Animals deficient in copper or exposed to a high dietary ratio of zinc to copper, which can produce a relative copper deficiency, are hypercholesteremic and hyperuricemic, and have glucose intolerance and abnormalities of the electrocardiogram. Their hearts and arteries have abnormal connective tissue, lipid deposits, and inflammatory changes; they die suddenly, often with ruptured hearts. Hypercholesteremia and glucose intolerance have been found in men depleted of copper and in children with Menkes' disease, an inability to absorb copper.

Generation of a Vasoactive Substance in Human Plasma during Coagulation

A stimulant of vascular smooth muscle contraction was generated in fresh, citrated human plasma during activation of the clotting system. Plasma, exposed briefly to thromboplastin and Ca<sup>++</sup>, induced a contraction of isolated rabbit aorta and dog coronary arteries that was slow in development and persisted after washout. The contractile activity was not blocked by phenoxybenzamine, atropine, or angiotensin inhibitor, but was blocked when heparin or hirudin was incubated with the plasma. The contractile stimulant produced in the plasma was short-lived (<3 min) and paralleled the appearance of thrombin in plasma. Purified human α-thrombin also induced a sustained contraction in these blood vessels that was not inhibited by phenoxybenzamine, atropine, or angiotensin inhibitor, but was blocked by hirudin. Partial relaxation of the thrombin-treated blood vessel was achieved by the addition of heparin. These results suggest that this vasoactive component of thromboplastin-activated human plasma is α-thrombin. Because of its potent and persistent effects, thrombin-induced vasospasm may be an important mechanism in the etiology of ischemic heart disease.

Haemostatic factors associated with ischaemic heart disease in men aged 45 to 64 years. The Speedwell study.

In the Speedwell study set up to examine primarily the relation of plasma lipids and ischaemic heart disease in men aged 45 to 64 years drawn randomly from the practices of 16 general practitioners, various haemostatic factors which may contribute both to thrombogenesis and atherogenesis were measured. Fibrinogen measured nephelometrically and plasma viscosity were positively associated with the prevalence of ischaemic heart disease. Antithrombin III was negatively associated with the prevalence of ischaemic heart disease. These associations were statistically significant at the 1% level of probability. Fibrinogen measured by a clotting method and the heparin neutralising activity of platelet poor plasma had negative and positive associations with ischaemic heart disease, respectively, but neither association achieved statistical significance. Because of the interrelation of these variables and also age, a multiple logistic regression analysis was undertaken separately for the two measures of fibrinogen. The negative association of "clottable' fibrinogen and the positive association of plasma viscosity with the prevalence of ischaemic heart disease were confirmed and both were statistically significant at the 5% level of probability. Apart from age the independent association of the other variables with ischaemic heart disease did not achieve statistical significance. Fibrinogen measured by both methods had positive and statistically significant associations with serum total cholesterol, but no associations with serum total triglycerides, smoking, or alcohol consumption. "Clottable' fibrinogen had an inverse and statistically insignificant association with serum high density lipoprotein cholesterol. The observed associations support the concept of the involvement of some haemostatic factors in the aetiology of ischaemic heart disease, and these associations are now being examined more critically in a longitudinal study.

Abnormal electrocardiograms in rats deficient in copper

According to a new hypothesis based on epidemiologic observations, iatrogenic maneuvers, natural occurrences, and animal experiments, absolute or relative deficiency of copper is of prime importance in the etiology of ischemic heart disease. Male weanling rats were made copper deficient with a purified diet containing 0.79 microgram Cu/g diet and containing all other nutrients known to be essential. Deficiency was verified by a 39% increase in cholesterolemia. Electrocardiograms of copper-deficient rats showed several abnormalities including S-T segment depression for one-third to one-half of the R-R interval, bundle branch block with R waves three times normal height and width, Q waves, and second- and third-degree heart block. Copper deficiency shortened the lives of the rats by 73%. Copper deficiency is the only nutritional insult that has produced rapid unfavorable alterations in lipid metabolism, cardiac and arterial anatomy, and cardiac electrophysiology. Copper metabolism may be important in the etiology of ischemic heart disease and in the arrhythmias associated with the consumption of liquid-protein diets.

Free adrenaline and noradrenaline excretion related to occupational stress.

Urinary levels of free adrenaline and noradrenaline were measured in two groups of healthy male industrial workers exposed to alternate four-day periods of working conditions with and without time stress, to test the hypothesis that the sympathetic nervous system is overactivated by occupational stress. Thirty confectionary workers alternated piece-work (payment by results) and work with a fixed daily wage while 30 metal workers alternated work on an assembly line with work off it. Under time stress urinary free adrenaline was 450 per cent and noradrenaline 230 per cent of the levels for similar work without time stress but involving equal oxygen consumption. These differences were statistically highly significant and they persisted on retesting after six months of alternating work regimens. They support the concept that occupational stress in industrial workers influences the adrenosympathetic system and they indicate a possible method for assessing the effects of high levels of sympathetic activity on the aetiology of ischaemic heart disease.

Fats and atheroma: a retrial.

The controversy over medical endorsement of dietary measures to reduce cholesterol intake has been reconsidered. The results of several published reports that apparently do not confirm the association between diet, cholesterol concentrations, and ischaemic heart disease (IHD) were found to be largely inapplicable to the argument. Results of primary prevention trials, however, suggested that lowering the cholesterol concentration had a beneficial effect in reducing morbidity from IHD. The "average Western diet" is particularly associated with accelerated or premature atherosclerotic disease, yet the saturated fatty acid component of the diet may be only one of several factors relevant to IHD. Such diets are usually high in refined carbohydrate and total energy intake. Disordered nutrition generally, and other environmental and constitutional factors seem to be important in the aetiology of IHD. A prudent diet, incorporating decreased intake of fats, simple sugars, and refined carbohydrate, with polyunsaturated fats comprising less than 25% of total energy intake, may be the best method of reducing the incidence of IHD and other diseases of overnutrition.

Aggregation of Deaths from Ischaemic Heart Disease among First and Second Degree Relatives of 108 Males and 42 Females with Myocardial Infarction

ABSTRACT. The occurrence of deaths due to ischaemic heart disease (IHD) among first and second degree relatives of coronary patients and among relatives of an equal number of matched controls was studied on the basis of death certificates. The propositi were 108 males and 42 females, who had developed myocardial infarction (MI), males before 65 years of age and females before 70. When compared with controls, a 1 1/2‐fold higher death rate was found among first degree relatives of the propositi and a lower average age at death. The difference in death rate between second degree relatives was not significant, except for maternal brothers. When compared with the death rate due to IHD in the general population, the increase in risk to first degree relatives of propositi was nearly 3‐fold over the expected value, and 1 1/2‐fold to second degree relatives. The age of the propositi at onset of MI did not affect the risk to relatives, whereas sex‐related influence was significant. To first degree relatives of male propositi the risk increase was up to 5‐fold over the expected value. The risk increase was found to be greatest to first degree male relatives of female propositi, or over 7‐fold to fathers and brothers. Mothers and sisters of both male and female propositi showed a 4–5‐fold risk increase over the expected value. The risk increase to second degree relatives was 2 1/2‐fold over the expected value to maternal brothers of male propositi and 4‐fold to such brothers of female propositi. The relatives of controls showed a coronary mortality close to that of the general population. Familial clustering of coronary deaths was found in 8.7% of the families of the propositi and in 4.7% of the families of the controls. The findings of the present study indicate a substantial genetic component in the overall aetiology of IHD, which is more prominent in families of female propositi but hardly of a magnitude to warrant genetic counseling.

Coronary ostium outside the aortic sinus. A factor in the aetiology of ischaemic heart disease?

Coronary ostium outside the aortic sinus. A factor in the aetiology of ischaemic heart disease?

The role of diabetogenic hyperinsulinism in nocturnal angina pectoris, with special reference to the etiology of ischemic heart disease.

Journal of the American Geriatrics SocietyVolume 15, Issue 6 p. 545-555 Article THE ROLE OF DIABETOGENIC HYPERINSULINISM IN NOCTURNAL ANGINA PECTORIS, WITH SPECIAL REFERENCE TO THE ETIOLOGY OF ISCHEMIC HEART DISEASE* H. J. Roberts M.D., Corresponding Author H. J. Roberts M.D. West Palm Beach, FloridaDirector, Palm Beach Institute for Medical Research; Consulting Staff, St. Mary's Hospital, West Palm Beach.Address: Palm Beach Institute for Medical Research, Inc., 304 Twenty-Seventh Street, West Palm Beach, Florida 33407.Search for more papers by this author H. J. Roberts M.D., Corresponding Author H. J. Roberts M.D. West Palm Beach, FloridaDirector, Palm Beach Institute for Medical Research; Consulting Staff, St. Mary's Hospital, West Palm Beach.Address: Palm Beach Institute for Medical Research, Inc., 304 Twenty-Seventh Street, West Palm Beach, Florida 33407.Search for more papers by this author First published: June 1967 https://doi.org/10.1111/j.1532-5415.1967.tb01194.xCitations: 4 †From the Mannow Research Laboratory, Palm Beach Institute for Medical Research, West Palm Beach. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume15, Issue6June 1967Pages 545-555 RelatedInformation

Metabolic differences between starch and sucrose.

SINCE 1957, papers from this department have stressed that the dietary factor involved in the aetiology of ischaemic heart disease is likely to be sugar (sucrose) rather than fat1. The evidence incriminating dietary sugar—now quite strong—is chiefly epidemiological. Investigations of populations show that the rise in the incidence of the disease coincides with the rise in the consumption of sugar and not of fat2–4. Again, during investigations of individuals we have shown that the disease is most likely to occur in those that have been eating a great deal of sugar5.

Tobacco and other factors in the etiology of ischemic heart disease in man Results of a retrospective survey

MANY studies have emphasized the role of tobacco in ischemic heart disease, but their conclusions differ on several points. Moreover, tobacco has usually been considered in isolation, without taking account of other etiological factors. The present work, divided into three parts, sets out to study: (1) the role of tobacco; (2) the role of other etiological factors-blood pressure, body build, blood fats; and (3) the role of tobacco in relation to these other factors. It is based on an investigation, extending from 1958 to 1963, of which some preliminary results in relation to tobacco have already been published [l].