Etiology Of Ischemic Heart Disease Research Articles

A follow-up program in patients after hospitalization for heart failure: long-term health related quality of life and associated factors.

The well-being of individuals with chronic heart failure (HF) is significantly influenced by their health-related quality of life (HRQoL), which serves as a crucial measure indicating how HF affects their daily activities. Monitoring programs aimed at reducing the number of hospitalizations and improving functional conditions are currently being offered to patients with chronic HF. To examine the long-term health-related quality of life changes in patients with heart failure enrolled in a follow-up program after hospitalization and to evaluate the factors associated with quality of life of patients with heart failure. This prospective study was conducted between 2019 and 2020 at the Department of Cardiology of Lithuanian University of Health Sciences. Patients were divided into two groups: Group I consisted of 71 patients (60.2%) where the Minnesota Living with Heart Failure Questionnaire (MLHFQ) score decreased by more than 10 points at 4th visit if compared to the 1st one; and Group II consisted of 47 patients (39.8%) where the MLHFQ score remained unchanged or increased by less than 10 points at the 4th visit if compared to the 1st visit. Statistically significant differences were observed between groups. In Group II, a history of myocardial infarction was more frequent (p = 0.038), and there was a significantly higher occurrence of significant coronary artery disease (p = 0.006). Laboratory parameters indicating liver function exhibited statistically significant deterioration among patients in Group II. Specifically, AST (p = 0.050), ALT (p = 0.010), and GGT (p = 0.031) levels significantly increased. Upon analyzing the echocardiographic data, a statistically significant difference was found between the groups in relation to the left ventricular ejection fraction (LVEF) (p = 0.043) and TAPSE (p = 0.031). An analysis of changes in dimensions related to QoL was conducted during the long-term follow-up program, which revealed statistically significant differences between groups in overall changes based on the MLHFQ (p < 0.001). This difference was also observed across all dimensions, including the emotional, physical, and social aspects (p < 0.001). Patients who had a higher LVEF at baseline, as well as those with an etiology of ischemic heart disease (IHD), better liver function, and fewer manifestations of edema, demonstrated a statistically significant improvement in their quality of life throughout the course of the patient monitoring program.

D-Dimer Is Associated With Coronary Microvascular Dysfunction in Patients With Non-obstructive Coronary Artery Disease and Preserved Ejection Fraction.

BackgroundCoronary microvascular dysfunction (CMVD), an important etiology of ischemic heart disease, has been widely studied. D-dimer is a simple indicator of microthrombosis and inflammation. However, whether an increase in D-dimer is related to CMVD is still unclear.Materials and MethodsThis retrospective study consecutively enrolled patients with myocardial ischemia and excluded those with obstructive coronary artery. D-dimer was measured at admission and the TIMI myocardial perfusion grade (TMPG) was used to distinguish CMVD. Patients were divided into the two groups according to whether the D-dimer was elevated (>500 ng/ml). Logistic models and restricted cubic splines were used to explore the relationship between elevated D-dimer and CMVD.ResultsA total of 377 patients were eventually enrolled in this study. Of these, 94 (24.9%) patients with CMVD had older age and higher D-dimer levels than those without CMVD. After full adjustment for other potential clinical risk factors, patients with high D-dimer levels (>500 ng/ml) had a 1.89-times (95% CI: 1.09–3.27) higher risk of CMVD than patients with low D-dimer levels. A non-linear relationship was found between concentrations of D-dimer and CMVD. With increased D-dimer level, the incidence of CMVD increased and then remained at a high level. Stratified analysis was performed and showed similar results.ConclusionElevated D-dimer level is associated with the incidence of CMVD and potentially serves as a simple biomarker to facilitate the diagnosis of CMVD for patients with angina.

Knowledge regarding Heart Failure: A Reflection on Current Disease Knowledge State among Iranian Patients with Heart Failure

Background: Heart failure (HF) is a serious problem with an increasing prevalence globally. Low level of HF knowledge may cause low compliance and low quality of life and, poor self-care. On the other hand, assessing the level of HF knowledge is necessary in order to apply educational programs. Aims and objectives: the aim was to determine knowledge regarding HF among Iranian patients with HF. Study Design: This was a cross sectional study. Setting: We conducted this study at the HF clinic of Tehran Heart Center (THC) affiliated with Tehran University of Medical Sciences (TUMS, Tehran, Iran). Materials and Methods: In this cross-sectional study, 190 patients older than 18 years old, with confirmed diagnosis of HF for at least 3 months by an HF specialist, NYHA function class II to IV and an ability of reading and writing Farsi language were included during June 2017 and January 2018 by consecutive sampling. Data were gathered in a short form, including demographic and clinical variables. Knowledge regarding HF was measured by the Dutch HF knowledge scale (Cronbach’s alpha=0.62) with 15- multiple choice item. The score range varied between 0 (no knowledge) and 15 (optimum knowledge). Scores were reported totally and in 3 areas of knowledge. Scores higher than the median was considered as higher knowledge. Statistics: The SPSS software version 16 was used to describe data. Normality of continuous variables was checked by the Kolmogorov-Smirnoff test. Frequency and partial frequency distribution were used to describe Categorical variables. While, we used mean, median, standard deviation, and IQR for describing continuous variables. Results: From June 2017 to January 2018, 160/190 patients with median age (IQR) of 59 (16) years old participated in the study (response rate of 84.2%). 67.5% of study patients were male (83.5%). 87.5% of then were married. The majority of patients were with NYHA function class II (60.6%), and with an etiology of ischemic heart disease (65.0%). The median and IQR of total, general, HF treatment, and symptoms/ symptom recognition knowledge were 8 (7-10), 12 (9-14), 2 (1.25-3), and 4 (3-5), respectively. Low level of total, general, HF treatment, and symptoms and symptom recognition knowledge among Iranian patients with HF were 55%, 60%, 58.8%, and 71.9%, respectively. Conclusion: Patients with HF had low levels of total, general, HF treatment, and symptoms/symptom recognition knowledge. Thus, there is an essential need to be improved by an appropriate intervention, especially on knowledge of symptoms /symptom recognition.

Diffuse coronary vasospasm in a patient with hypothyroidism

Coronary vasospasm is an important etiology of ischemic heart disease. Sometimes thyroid disorders may be associated with cardiovascular disease. The major cardiovascular changes that occur in hypothyroidism include a decrease in cardiac output and cardiac contractility, a reduction in heart rate, and an increase in peripheral vascular resistance. There are also significant changes in modifiable atherosclerotic risk factors, including hypercholesterolemia, diastolic hypertension, carotid intimal media thickness, and endothelial derived relaxation factor (nitric oxide), which accompany overt hypothyroidism. Here, we present a case of diffuse coronary arterial vasospasm in a patient with hypothyroidism.

Subgroups at high risk for ischaemic heart disease:identification and validation in 67 000 individuals from the general population.

The aetiology of ischaemic heart disease (IHD) is complex and is influenced by a spectrum of environmental factors and susceptibility genes. Traditional statistical modelling considers such factors to act independently in an additive manner. The Patient Rule-Induction Method (PRIM) is a multi-model building strategy for evaluating risk attributable to context-dependent gene and environmental effects. PRIM was applied to 9073 participants from the prospective Copenhagen City Heart Study (CCHS). Gender-specific cumulative incidences were estimated for subgroups defined by categories of age, smoking, hypertension, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol and triglycerides and by 94 single nucleotide variants (SNVs).Cumulative incidences for subgroups were validated using an independently ascertained sample of 58 240 participants from the Copenhagen General Population Study (CGPS). In the CCHS the overall cumulative incidences were 0.17 in women and 0.21 in men. PRIM identified six and four mutually exclusive subgroups in women and men, respectively, with cumulative incidences of IHD ranging from 0.02 to 0.34. Cumulative incidences of IHD generated by PRIM in the CCHS were validated in four of the six subgroups of women and two of the four subgroups of men in the CGPS. PRIM identified high-risk subgroups characterized by specific contexts of selected values of traditional risk factors and genetic variants. These subgroups were validated in an independently ascertained cohort study. Thus, a multi-model strategy may identify groups of individuals with substantially higher risk of IHD than the overall risk for the general population.

Renal function largely influences Galectin-3 prognostic value in heart failure

BackgroundGalectin-3 (Gal-3) has been associated with cardiac remodeling and heart failure (HF) prognosis. Renal function is also a well known HF prognostic indicator. The link between renal insufficiency, HF, and Gal-3 is not completely elucidated. Methods and resultsWe explored the association between Gal-3 and renal function in a cohort of 876 consecutive ambulatory patients with HF (mean age: 68years; mean left ventricular ejection fraction [LVEF]: 36%), 52.2% had HF etiology of ischemic heart disease. Circulating Gal-3 was highly correlated with estimated glomerular filtration rate (eGFR), calculated with either the chronic kidney disease-epidemiology (CKD-EPI) equation (r=−0.64) or the CKD-EPI-cystatin-C equation (r=−0.59) and with Cystatin-C levels (r=0.70), after adjusting for age, sex, New York Heart Association (NYHA) functional class, LVEF, and HF etiology (all p<0.001). Patients were stratified by CKD-EPI-eGFR (ml/min/1.73m2), as follows: ≥60 (n=218), 30 to 59 (n=434), and <30 (n=224). In these strata, Gal-3 significantly increased (median [IQR]: 12.3 [10.4–15.6]; 16.1 [13–19.8]; and 24.5 [20–33.8] ng/ml, respectively; trend p<0.001). This was independent of NYHA functional class (I–II and III–IV) and LVEF (<45% and ≥45%). Gal-3 was associated with mortality in univariate analyses, but after adjusting for CKD-EPI-eGFR, the hazard ratios were 1.10 (95% CI: 0.89–1.34, p=0.39) for all cause death, and 0.90 (95% CI: 0.68–1.21, p=0.50) for cardiovascular death. Similar results were obtained with eGFRs calculated with the CKD-EPI-cystatin-C equation. ConclusionCirculating Gal-3 was highly associated with renal function in outpatients with HF. The value of Gal-3 for HF prognosis declined after adjusting for renal function.

A COMPARATIVE STUDY OF ANTI-PHOSPHATIDYL INOSITOLE ANTIBODIES IN PATIENTS WITH MYOCARDIAL INFARCTION AND HEALTHY SUBJECTS

Immune system and inflamation is widely known to play a key role in the development and progression of cardiovascular diseases. Anti-Phospholipid (aPL) antibodies may act in the induction of immunological response leading to the development of Acute Myocardial Infarction (AMI). Anti-Phosphatidyl Inositole (PI) Antibody (Ab) has been seen in various diseases including rheumatoid arthritis, systemic lupus erythematosus and anti-phospholipid antibody syndrome. Although there are a few studies on the association of some autoantibodies with AMI, more epidemiological data are required to confirm their significance as independent risk factors in cardiovascular diseases. Moreover, the data on the relationship of autoantibodies with traditional risk factors of AMI is rare. The study of anti-PI Ab in AMI may lead to understand of etiology of ischemic heart disease. This study was conducted to determine whether prevalence of anti-PI Abs, in patients who had AMI and to analyze their association with traditional cardiovascular risk factors. The prevalence of anti-PI IgG and IgM in a well characterized group of patients with AMI as a case group and in age and sex matched healthy subjects as control group. Sera from the case and the control groups were tested to evaluate the presence of IgG and IgM isotypes to anti-PI by ELISA method. The prevalence of anti-PI IgG and also IgM in the case group resulted significantly higher than in the control group with AMI (p<0.005). The findings of this study suggest that anti-PI Abs seemed to have a role in AMI independent risk factors for AMI and may represent a link between autoimmunity and atherosclerosis in patients with AMI. Comprehensive studies are recommended to explore the exact role of anti-PI Abs in AMI.

Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease

Conventionally, ischemic heart disease (IHD) is equated with large vessel coronary disease. However, recent evidence has suggested a role of compromised microvascular regulation in the etiology of IHD. Because regulation of coronary blood flow likely involves activity of specific ion channels, and key factors involved in endothelium-dependent dilation, we proposed that genetic anomalies of ion channels or specific endothelial regulators may underlie coronary microvascular disease. We aimed to evaluate the clinical impact of single-nucleotide polymorphisms in genes encoding for ion channels expressed in the coronary vasculature and the possible correlation with IHD resulting from microvascular dysfunction. 242 consecutive patients who were candidates for coronary angiography were enrolled. A prospective, observational, single-center study was conducted, analyzing genetic polymorphisms relative to (1) NOS3 encoding for endothelial nitric oxide synthase (eNOS); (2) ATP2A2 encoding for the Ca2+/H+-ATPase pump (SERCA); (3) SCN5A encoding for the voltage-dependent Na+ channel (Nav1.5); (4) KCNJ8 and KCNJ11 encoding for the Kir6.1 and Kir6.2 subunits of K-ATP channels, respectively; and (5) KCN5A encoding for the voltage-gated K+ channel (Kv1.5). No significant associations between clinical IHD manifestations and polymorphisms for SERCA, Kir6.1, and Kv1.5 were observed (p > 0.05), whereas specific polymorphisms detected in eNOS, as well as in Kir6.2 and Nav1.5 were found to be correlated with IHD and microvascular dysfunction. Interestingly, genetic polymorphisms for ion channels seem to have an important clinical impact influencing the susceptibility for microvascular dysfunction and IHD, independent of the presence of classic cardiovascular risk factors.

An application of the patient rule-induction method for evaluating the contribution of the Apolipoprotein E and Lipoprotein Lipase genes to predicting ischemic heart disease.

Different combinations of genetic and environmental risk factors are known to contribute to the complex etiology of ischemic heart disease (IHD) in different subsets of individuals. We employed the Patient Rule-Induction Method (PRIM) to select the combination of risk factors and risk factor values that identified each of 16 mutually exclusive partitions of individuals having significantly different levels of risk of IHD. PRIM balances two competing objectives: (1) finding partitions where the risk of IHD is high and (2) maximizing the number of IHD cases explained by the partitions. A sequential PRIM analysis was applied to data on the incidence of IHD collected over 8 years for a sample of 5,455 unrelated individuals from the Copenhagen City Heart Study (CCHS) to assess the added value of variation in two candidate susceptibility genes beyond the traditional, lipid and body mass index risk factors for IHD. An independent sample of 362 unrelated individuals also from the city of Copenhagen was used to test the model obtained for each of the hypothesized partitions.

Graft coronary artery disease is strongly related to the aetiology of heart failure and cellular rejections.

To identify risk factors for the development of coronary artery disease after heart transplantation. In consecutive heart transplanted patients, who underwent coronary angiography at the first year follow-up, the aetiology of heart failure in 113 was ischaemic heart disease or dilated cardiomyopathy. Development of clinically significant graft coronary artery disease was analysed vs recipient and donor pre- and post-transplantation variables. At 1, 5 and 9 years follow-up, coronary artery disease had developed in 4%, 16%, and 20% of the included patients, respectively. Among patients with ischaemic heart disease as the aetiology of heart failure, 38% developed graft coronary artery disease, while the corresponding figure for patients with dilated cardiomyopathy was 9% (P<0.001) during 9 years of follow-up. In multivariate regression analysis, the aetiology of ischaemic heart disease and the number of cellular rejections were independent predictors of developing graft coronary artery disease, with risk ratios of 5.8, (95% confidence interval of 2.2-14.8 (P=0.0003)) and 3.3, (95% confidence interval of 1.7-6.5 (P=0.0004)), respectively. Classical risk factors for coronary artery disease did not influence the development of graft coronary artery disease. Ischaemic heart disease as the aetiology of heart failure and the number of cellular rejections were powerful independent predictors of development of graft coronary artery disease following heart transplantation. The low incidence of graft coronary artery disease among patients with dilated cardiomyopathy implies that coronary angiography after heart transplantation can be made on a more selective basis.

Physical and geometrical modeling for image-based recovery of left ventricular deformation.

Information about left ventricular (LV) mechanical performance is of critical importance in understanding the etiology of ischemic heart disease. Regional measurements derived from non-invasive imaging to assist in assessing this performance have been in use for decades, and certain parameters derived from these measurements often are useful clinically, as they correlate to some extent with gross physiological hypotheses. However, relatively little work has been done to date to carefully understand the relationship of regional myocardial injury to the local mechanical performance of the heart as derived from image data acquired non-invasively for a particular patient in 3 spatial dimensions over time. This paper describes efforts to take advantage of recent developments in 3D non-invasive imaging and biomechanical modeling to design an integrated computational platform capable of assembling a variety of displacement and velocity data derived from each image frame to deform a volumetric model representation of a portion of the myocardium. A brief description of the reasoning behind this strategy an overview of the approach and some initial results are described.

Dietary determinants of ischaemic heart disease in health conscious individuals

ObjectiveTo investigate dietary determinants of ischaemic heart disease (IHD) in health conscious individuals to explain the reduced risk in vegetarians, and to examine the relation between IHD and body mass...

The relationship between cigarette smoking and cardiovascular risk factors in peripheral arterial disease compared with ischaemic heart disease: The Edinburgh Artery Study

Cigarette smoking is probably the most important risk factor for the development of peripheral arterial disease, but it may be less important in the aetiology of ischaemic heart disease. The objectives of this study were to determine whether any other cardiovascular risk factors showed a significant interaction with cigarette smoking which would explain the greater association between smoking and peripheral atherosclerosis. One thousand five hundred and ninety-two subjects aged 55-74 years were selected randomly from the age-sex registers of 10 general practices in Edinburgh, Scotland. The presence of peripheral arterial disease was determined by the World Health Organisation questionnaire on intermittent claudication, the ankle brachial pressure index and a reactive hyperaemia test. Heart disease was identified by the patients' recall of a doctor diagnosis of angina or myocardial infarction. There were 131 subjects with peripheral arterial disease but no ischaemic heart disease, and 169 with heart disease without peripheral disease. Significantly more smokers occurred in the peripheral than the heart disease group (P <0.01), and in current smokers the age and sex adjusted odds ratio were highly significant for peripheral arterial disease (odds ratio 5.09, 95% confidence interval 2.97-8.72, P<0.001), but not for heart disease (odds ratio 1.72, 95% confidence interval 0.98-2.33, P>0.05). Subjects with lower limb disease also had higher systolic pressures (P<0.001), serum high density lipoprotein cholesterol (P<0.01) and plasma fibrinogen (P<0.05). On logistic regression, adjusting for a range of individual risk factors had no significant impact on the effect of smoking. Plasma fibrinogen produced the biggest reduction in odds ratio (4.23, 95% confidence interval 2.44-7.35, in current smokers with peripheral arterial disease). Therefore the stronger association between smoking and peripheral arterial disease than ischaemic heart disease does not appear to be influenced by the other risk factors examined here, and must be explained by some other mechanism.

Serum bilirubin and risk of ischemic heart disease in middle-aged British men

The possibility that low concentrations of serum bilirubin may be associated with increased risk of ischemic heart disease has been examined in a prospective study of 7685 middle-aged British men. During 11.5 years there were 737 major ischemic heart disease (IHD) events. A U-shaped relationship was observed between serum bilirubin and risk of IHD. Low bilirubin was associated with several cardiovascular risk factors, in particular smoking, low concentrations of high-density lipoprotein cholesterol, low forced expiratory volume in 1 s, and low serum albumin. The U-shaped relationship persisted even after adjusting for several risk factors. Compared with men in the lowest fifth of the distribution (bilirubin < 7 mumol/L), those in the middle range (8-9 mumol/L) showed a 30% reduction in relative risk [RR = 0.68 (95% confidence intervals 0.51-0.89)] in IHD, whereas men in the top fifth (> 12 mumol/L) showed similar risk to the lowest fifth [RR = 0.99 (95% confidence intervals 0.73-1.34)], which persisted after exclusion of men with bilirubin > 17 mumol/L. The significance of this U-shaped relationship is unclear, but it could be interpreted as support for the role of endogenous antioxidants in the etiology of IHD.

Medico-Legal Problems of Ischaemic Heart Disease and Myocardial Infarction

The medicolegal importance of ischaemic heart disease and myocardial infarction is summarized and discussed. Some theories of pathogenesis and aetiology of ischaemic heart disease, specially those which are more important and relevant to the medicolegal practice, are discussed. Results of the study of 33 cases of coronary artery atherosclerosis and myocardial infarction at different stages of development are presented. The condition of the coronary arteries and the myocardium is examined on gross and microscopical levels. Pathological findings are correlated with the clinical data obtained from the case histories and the summaries of the necropsy requests. No good correlation exists between the observed pathological changes and the clinical age of the infarction and, in most instances, the latter appears younger than the age estimated on the pathological ground alone. As far as the age of the infarction is concerned, most special histochemical staining methods are not preferable to the routine haematoxylin and eosin method. However, the former are efficient in demonstrating and confirming certain aspects of the infarction which cannot be ascertained by the latter method of staining. Pathological alterations associated with myocardial infarction at successive ages are explained and various methods of estimating the time of the infarction are discussed. Thus, gross and microscopical appearances of the acute, organizing and healed myocardial infarction are illustrated by photographs and the forensic applications of these morphological changes are discussed. Lastly, a rare case of an acute myocardial infarction associated with a heat stroke is presented and the medicolegal problems resulting from this case are discussed.

Dietary saturated or polyunsaturated fat and copper deficiency in the rat

Dietary fat-type and copper (Cu) deficiency have been independently identified as potentially important factors in the etiology of ischemic heart disease (IHD); a disease that has been linked to inflammation and oxygen free radical (OFR) mediated damage. Group (n = 6) of male, weanling, Wistar rats were provided ad libitum with deionized water and control or low Cu diets containing (200 g/kg) either saturated or polyunsaturated fatty acids (SFA or PUFA, respectively) for 56 d. Measurement of several indices of Cu status indicated that both groups fed the low Cu diets were Cu-deficient. SFA consumption resulted in significantly increased hepatic Cu (p less than 0.001) and iron (Fe) (p less than 0.001) concentrations and xanthine oxidase activity (p less than 0.05) and significantly decreased hepatic glucose-6-phosphate dehydrogenase activity (p less than 0.001). Although Cu deficiency resulted in significantly decreased hepatic copper-zinc superoxide dismutase (CuZnSOD) activity (p less than 0.01), no significant effect on the activities of the other hepatic antioxidant enzymes, manganese superoxide dismutase, catalase, and glutathione peroxidase, or glutathione reductase, were observed. Cu deficiency also resulted in significantly decreased hepatic Cu levels (p less than 0.001) and cytochrome c oxidase activity (p less than 0.01). No significant difference in hepatic thiobarbituric acid reactive substances (TBARS), a measure of lipid peroxidation, was found between groups consuming SFA or PUFA, but both Cu-deficient groups exhibited significantly increased hepatic TBARS (p less than 0.001), compared to controls. This was probably owing to the significantly decreased hepatic CuZnSOD activity observed in the Cu-deficient, compared to control animals.

Milk consumption, lactose and copper in the aetiology of ischaemic heart disease

Milk is a poor source of copper — a nutrient which is known to be limiting or marginal in many western diets. Lactose (a major nutritional constituent of milk) may interfere with copper utilization in milk and in the overall diet. It is postulated that the strong association between the consumption of milk and dairy products (especially fresh milk and non-fermented milk products) and the incidence of ischaemic heart disease (IHD) indicates a central role for a dietary copper deficiency in the aetiology of this disease.

Selenium in ischaemic heart disease.

Ecological between-area comparisons, hospital-based case-control studies and cross-sectional angiography studies have provided data on the role of selenium (Se) deficiency in the aetiology of ischaemic heart disease (IHD), but this evidence is, at best, suggestive because of the potential selection biases and the lack of certainty of the temporal direction of the observed associations. Out of the four cohort-based population studies published so far, one observed a moderate association between a reduced serum Se and an increased risk of IHD and all cardiovascular (CVD) deaths, one was equivocal and two did not find any association between serum Se and IHD. There are, however, several potential sources of biases acting towards the null hypothesis in these studies. In the pooled data of the two separate cohorts from eastern Finland including 377 people who experienced a CVD death or a non-fatal myocardial infarction and equally many event-free risk-factor matched controls, people with serum Se of less than 45 micrograms/l had a 1.7-fold (95% confidence interval 1.2-2.7) risk of an CVD event compared to those with higher serum Se. This association could, however, be explained by the covariation of Se with other nutrients, as for example n-3 polyunsaturated fatty acids. As the evidence concerning the role of serum Se in IHD is inconclusive, we need new epidemiological studies to test the association and experiments exploring the possible mechanisms.

The Eskimo diet. Prophylactic effects ascribed to the balanced presence of natural cis unsaturated fatty acids and to the absence of unnatural trans and cis isomers of unsaturated fatty acids

In addition to the well recognised roles of eicosapentaenoic acid and possibly docosahexaenoic acid, there are two other major important, but unrecognised, features of the traditional Eskimo staple diet namely that (i) it contains the unsaturated fatty acids (UFA) cis oleic, cis linoleic and cis alpha-linolenic as well as their respective C20 and C22 metabolites in physiologically optimal concentrations and, (ii) it is virtually totally devoid of unnatural and potentially hazardous trans and cis isomers of these fatty acids. Large quantities of unnatural trans and cis isomers of UFA are found in the Western diet as partially hydrogenated UFA in many foods. These isomers are formed (i) during the manufacture of margarines and related compounds, (ii) as food contaminants during excessive heating of cooking oils for deep-frying and other excessive heat-requiring mass food preparation procedures and (iii) it is suggested, as the result of excessive feeding with an unnatural diet of ruminants and non-ruminants for increased meat and/or milk production and of poultry for increased egg and/or meat production. These isomers have been shown to display potentially hazardous metabolic effects which include the competitive inhibition of UFA metabolism at various steps and have been causally implicated in the etiology of ischemic heart disease and cancer. It is suggested that the myth of the safety of trans fatty acids arises from misinterpretation of the observation that increasing dietary cis linoleic acid reduces the toxic effects of trans UFA. It is suggested that the decrease of 20% in the ischemic heart disease mortality in the USA during the past two decades is directly related to a shift in the dietary ratio of unnatural trans and cis UFA isomers: cis linoleic acid in favour of the latter. It is predicted that this ratio will be found to correlate with ischemic heart disease patterns in other countries. Eskimos consume the bulk of their food frozen, raw or dried, seldom boiled, but never deep-fried or after exposure to excessive heat. Moreover the proportionality of cis UFA and their metabolites in their traditional staple diet would render gross tissue UFA utilization relatively independent of desaturase enzyme activity. In the Eskimo tissues these enzymes would function to make the minute, critical UFA metabolic adjustments required to (i) ensure the presence of structural UFA in membranes in functionally optimal quantities and, (ii) ensure the synthesis of eicosanoids from dihomogamma-linolenic acid, arachidonic acid and eicosapentaenoic acid in balanced, optimal physiological concentrations for the genetic make-up of Eskimos. It is therefore proposed that the composition of the Eskimo diet, specifically with regard to its content of natural cis UFA and of their respective cis longer chain metabolites, could account for its reported prophylactic effects. It is further proposed that regular dietary supplementation with longer chain UFA metabolites will correct the hazardous metabolic effects caused by the presence of unnatural trans and cis UFA in the tissues of humans chronically consuming a Western diet. By thus mimicking the Eskimo diet, therapeutic and prophylactic effects could be achieved in a wide range of Western degenerative diseases including cardiovascular disease and cancer.

Aspirin hypocholesterolemia associated with increased microsomal copper in liver

Aspirin was fed to rats (2.4 g/kg of diet) in a diet deficient in copper because of an hypothesis linking the etiology of ischemic heart disease to copper metabolism and because of the apparently protective effect of aspirin in this disease. Cholesterol was measured by fluorometry and copper was measured by atomic absorption spectrometry. Aspirin decreased cholesterol in plasma approximately 18% (p<0.003) in each of two experiments. Copper in liver microsomes was doubled by aspirin (p<0.002). The effects of aspirin were compared to those of clofibrate in a similar experiment (Drug-Nutrient Interactions 2:131, 1983) and to other chemicals that alter both cholesterol metabolism and copper metabolism. Effects on copper may be central to the action of cholesterotropic agents.