Causation Of Coronary Heart Disease Research Articles

Evaluation of Iron Profile among Ischemic Heart Disease Patients in Shendi City, Sudan

Background: Ischemic heart disease (IHD), is a group of diseases that includes: stable angina, unstable angina, myocardial infarction, and sudden cardiac death. It is within the cluster of cardiovascular conditions of which it is the multiple expected kinds. Iron is an essential trace element. It has a pivotal role in maintaining various cellular functions and enzyme reactions; whereas, iron overload has been known as a risk factor in the progression of atherosclerosis. Abnormal deposition of iron in the heart cause hemochromatosis and dilated cardiomyopathy and this causes ischemic heart disease. This study aimed to investigate the role of serum iron, serum ferritin, and total iron-binding capacity (TIBC) in the causation of coronary heart disease (CHD) and their relationship with other risk factors of CHD. Methods: This is a cross-sectional case-control prospective analytical study conducted at Al-Mc Nemir University Hospital in Shendi town to evaluate the iron profile in ischaemic heart disease patients in the period between (March 2018—July 2018). The study included (50) patients who were diagnosed with ischaemic heart disease and the study groups were compared with a mean of the normal value. Serum iron, ferritin, and TIBC were estimated by spectrophotometer. Data was collected using a structured face-to-face questionnaire and the (SPSS) version (11.5) program was used for data analysis. Results: The study revealed that the ischaemic heart disease patients were; (40%) male and (60%) female, and the mean age was (57.612 ± 28.24), with a range of (36-65) years distributed as (96%). The study showed that the mean of s. iron was 203.9ug/dl (p.value 0.170), the mean of s. ferritin was 207.6ug/dl(p.value 0.447), the mean of TIBC was 663.0ug/dl( p.value 0.281) when compare with the mean of normal value. No significant difference was found between iron profile and CHD. Serum iron and serum ferritin levels are elevated in patients with CHD when compared with normal values. TIBC levels were lower in patients than normal values. When body iron was analogized with different risk factors (like smoking, hypertension, diabetes mellitus, tobacco, etc) of the condition it was found to be seriously raised. Conclusion: The study concluded that the level of serum iron, ferritin, and TIBC might not be associated with coronary heart disease.

Prevalence of Hypertension and Its Risk Factors among Adults in Rural Community: A Cross-Sectional Study

Introduction: Hypertension is a chronic condition of concern due to its role in the causation of coronary heart disease, stroke and other vascular complications. Objectives of this study were to find out prevalence of hypertension among adults of rural community and association between hypertension and its risk factors.
 Methodology: Cross sectional community-based study was done with a sample of 501 adults between 18 to 60 years of age including both men (244) and women (257). A pretested semi-structured proforma was used collect data by trained doctors.
 Results: The overall prevalence of hypertension was found to be 32.13 %. Higher prevalence found among males (34%), age group 51-60 year (49.5%) and in class III SES (38.9%). Hypertension was found to be significantly associated with family history of hypertension (OR=2.41, CI= 1.50-3.80), smoking (OR= 1.78, CI=1.08-2.93), alcohol use (OR=1.8, CI=1.20-2.60), high salt intake (OR= 3.2, CI=1.80-5.45), junk food consumption (OR=2.40, CI=1.63-3.52), physical inactivity (OR=2.8, CI=1.90-4.14), overweight (OR=3.14, CI=2.11-4.66) and obesity (OR=3.78, CI=2.41-5.95).
 Conclusion: Increasing prevalence of hypertension in rural areas is major public health problem. Appropriate strategies are needed to create awareness regarding risk factors of hypertension.

Prevalence and Risk Factors of Hypertension Among Adults in Nagarjun Municipality of Kathamandu District

Hypertension plays a persistent role in the causation of coronary heart disease, stroke, and vascular problems. Many factors like dietary, behavioral, psychological, environmental, genetic, etc have a direct or indirect influence on hypertension. The available evidences shows a higher prevalence of hypertension in Nepal. The objective of this study was to assess the prevalence and risk factors associated with hypertension among adults of Nagarjun Municipality. A descriptive cross-sectional study was conducted among adults of age 18 and above in Nagarjun municipality. A structured questionnaire was used to assess the risk factors and observation was done to determine blood pressure and anthropometric measurement. The data were entered and analyzed by (SPSS) software version 20. Chi-square test was used to identify the association. The overall prevalence of hypertension was 22.8% and prehypertension was 14.5%. More males were found to have hypertension (28.09%) compared to females (16.67%). Age, sex, religion, socio-economic status, ciggrate smoking, alcohol consumption, BMI, diabetes, family history of hypertension and cardio vascular disease was found to be significantly associated with hypertension. The preventive and intervention measures should be adopted to reduce the behavioral and biological risk factors which are directly related with the causation of hypertension.

Fat, Sugar, Whole Grains and Heart Disease: 50 Years of Confusion.

During the 1970s some investigators proposed that refined carbohydrates, especially sugar and a low intake of dietary fiber, were major factors in coronary heart disease (CHD). This suggestion was eclipsed by the belief that an excess intake of saturated fatty acids (SFA) was the key dietary factor, a view that prevailed from roughly 1974 to 2014. Findings that have accumulated since 1990 inform us that the role of SFA in the causation of CHD has been much exaggerated. A switch from SFA to refined carbohydrates does not lower the ratio of total cholesterol to HDL-cholesterol in the blood and therefore does not prevent CHD. A reduced intake of SFA combined with an increased intake of polyunsaturated fatty acids lowers the ratio of total cholesterol to HDL-cholesterol; this may reduce the risk of CHD. The evidence linking carbohydrate-rich foods with CHD has been steadily strengthening. Refined carbohydrates, especially sugar-sweetened beverages, increase the risk of CHD. Conversely, whole grains and cereal fiber are protective. An extra one or 2 servings per day of these foods increases or decreases risk by approximately 10% to 20%.

Role of lipids and free radicals in diabetic with hypertension and smokers for causation of coronary heart disease

Introduction: The major independent risk factors for the development of atherosclerosis are the plasma cholesterol concentration, triglyceride, cigarette smoking, hypertension and diabetes, which are by them self’s risk factor for coronary heart disease. Cardiovascular disease (CVD) threatens to cripple India’s workforce and stunt India’s growth if timely and appropriate public health measures are not instituted. Hyperglycemia, hypertension and cigarette smoking depletes natural antioxidants and facilitates the production of reactive oxygen species (ROS) which has the ability to react with all biological molecules and exert cytotoxic effects on cellular components that promotes and accelerate atherosclerosis. Hence the present study was aimed to find out collective effect of NIDDM, hypertension and cigarette smoking on lipid profile and oxidative stress in progression of CHD events. Materials and methods: We studied 50 healthy and 50 diabetes with hypertension and or smokers patients (i. e. had two or more CHD risk factors) patients with matched for age and body mass index. Blood samples were drawn after an overnight fast. W e estimated serum triglycerides,total cholesterol, HDL-c and LDL-c and VLDL- c values were calculated by Friedwald’s equation. We also estimated the total serum lipid peroxides by reaction with thiobarbituric acid. Results: In the control group I mean values of total cholesterol were 180.21 ± 18.13 mg %, LDL-c 106.60 ±18.2 mg%, serum triglycerides were 99.90 ± 16.14 mg %, HDL-c were 53.83 ± 16.42mg% and in the group II serum triglycerides 217.9 ± 19.1 mg% and were significantly increased as compared to group I. The serum HDL-c group II 29.6 ± 8.07mg % were significantly decreased as compared to group I (P is<0.05). The serum lipid peroxides in the group 2nd (296.9.±60.10) were significantly increased as compared to group 1st (180.96±35.16). Conclusion: It can be concluded that patients of NIDDM with hypertension, smoking have higher total serum cholesterol, serum triglycerides, serum lipid peroxides (MDA), LDL- c and VLDL-c with lower HDL- c. These can be corrected, treated by dietary and life style modification before the development of end organ damage. For realization of exact role of lipid profile and oxidative stress further higher level studies should be done.

The prevalence of hypertension and its associated risk factors among adults in rural Mandya, Karnataka, India

Background: Hypertension is the commonest cardiovascular disorder due to its role in the causation of coronary heart disease, stroke and other vascular complications. In India, hypertension is one of major risk factors for cardiovascular mortality and is attributed for 10% of all deaths. Increasing prevalence in hypertension is expected due to economic transition, increased population growth, ageing, behavioural risk factors such as, unhealthy diet and excessive alcohol consumption. Awareness of hypertension and risk factors for hypertension is less among rural population. Proposed study addresses the risk factors and awareness of the rural community. Methods: Cross sectional study was conducted over a period of one year from June 2013 to May 2014 among adults from randomly selected villages in the Keragodu primary health centre area. House to house survey was conducted among adults in each village and was examined for hypertension and interviewed regarding the risk factors of hypertension using a pre tested, semi structured questionnaire. Results: Among 1786 study subjects, 38.6% were males and 61.4% were females. The prevalence of hypertension was observed to be 25.9%. Prevalence increased as the age increased. The prevalence of hypertension was high among obese, those who had history of diabetes mellitus. Among the study subjects 24.1% (112) were aware of their hypertensive status, of these 56.3% were on regular treatment . Conclusions: The prevalence of hypertension was 25.9%. Various factors like increase in age, obesity, history of diabetes are implicated in the occurrence of hypertension.

Prevalence of hypertension and its risk factors among staff of Raichur Institute of Medical Sciences, Raichur

Background: Hypertension is a chronic condition of concern due to its role in the causation of coronary heart disease, stroke and other vascular complications. It is one of the important risk factors for cardio-vascular mortality, accounting for 20-30% of all deaths. Hypertension is an iceberg disease. To address this problem of hypertension, the theme for World Health Day, 2013 was “High Blood Pressure.” Aims & Objectives: To study the prevalence of hypertension and its risk factors among staff of Raichur Institute of Medical Sciences, Raichur. Materials and Methods: On the WORLD Health Day 2013, a hypertension screening camp was organized. A total of 163 teaching and non-teaching staffs actively and voluntarily participated in the camp. Hypertension and its risk factors were assessed using predesigned questionnaire - which included socio-demographic details and their family, dietary and personal history. Height, weight and blood pressure of the study participants were recorded. Results: Out of 163 participants, 101 (62%) were males and 62 (38%) were females. Majority, 79.1%, had mixed diet, 20.9% were vegetarians, and 18.4% of them added extra salt to the diet. Physical activity level was good among 27%, as they were exercising for ≥ 30minutes in a day. Prevalence of hypertension was 11.7 %, and 9.2% of staff had blood pressure in pre-hypertension range. Conclusion: Prevalence of hypertension was 11.7%, among which 6.7% were newly detected and 5% were previously diagnosed to have hypertension. Regular screening and health education camp are essential to curtail the rising problem of hypertension

Addressing the Burden of Disease Attributable to Air Pollution in India: The Need to Integrate across Household and Ambient Air Pollution Exposures

Addressing the Burden of Disease Attributable to Air Pollution in India: The Need to Integrate across Household and Ambient Air Pollution Exposures

Pro-inflammatory cytokine gene polymorphisms and threat for coronary heart disease in a North Indian Agrawal population

The association of IFN-γ (+874 A/T; rs2430561), TNF-α (−308 G/A; rs1800629) and TNF-β (+252 A/G; rs909253) with Coronary Heart Disease (CHD) has not been rigorously tested in Indian population. In the present study we sought to examine the role of these cytokines in the causation of CHD and their association with conventional CHD risk factors. A total of 138 case and 187 unrelated healthy controls aged 35 to 80years, matched on ethnicity and geography were collected from North Indian Agrawal population. Single nucleotide polymorphisms at the promoter TNF-α −308 G/A and the intronic IFN-γ +874 A/T were analyzed by allele-specific PCR, and the intronic TNF-β +252 A/G was analyzed by RFLP. Of the three selected polymorphisms, genotypic distribution of IFN-γ +874 A/T and TNF-β +252 A/G polymorphisms was significantly different between patients and controls in the present study. OR revealed statistically significant risk for CHD with respect to IFN-γ +874 T allele, whereas OR for TNF-β +252 A/G showed three fold risk in homozygous condition though not significant. No such trend could be observed for TNF-α −308 G/A polymorphism. Multivariate logistic regression after adjusting for all the confounders showed significant risk for CHD with the genotypes and genotypic combinations of all the three markers (albeit not significant with TNF-α). Increased risk for CHD was likely to be associated with interaction of IFN-γ with diastolic hypertension, TNF-α with diabetes and BMI, and TNF-β with serum triglyceride and very low density lipoprotein (VLDL) levels. The results suggest that these selected cytokine polymorphisms could possibly serve as potential bio-markers for CHD in conjunction with specific conventional risk factors.

Methylenetetrahydrofolate reductase polymorphism: An independent risk determinant of coronary heart disease in an endogamous population from Delhi (India)

summary Background & aims: Methylenetetrahydrofolate reductase catalyzes the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate in the folate metabolic pathway. Of the numerous polymorphisms reported worldwide in this gene, C677T and A1298C are the most extensively studied with respect to various complex disorders. The present study attempts to understand the effect of these two polymorphisms on the causation of coronary heart disease in a Mendelian population of a specific geographical area in India. Methods: The study was carried out using 100 cases and 100 age, sex, geography and ethnicity matched controls. Blood samples were subjected to biochemical and molecular analysis. Medical histories and anthropometric measurements were taken from all the enrolled subjects. Results: Cases and controls differed significantly (p-value <0.05) with respect to the polymorphisms at both the loci. Odds ratio revealed a significant 2.29 fold and 2.09 fold increased risk for coronary heart disease with regard to C677T and A1298C polymorphisms respectively. Conclusion: The study emphasizes that the MTHFR C677T and A1298C polymorphisms are independent risk factors for coronary heart disease in the selected community belonging to a specific geographical area of India.

Genetic Predisposition, Nongenetic Risk Factors, and Coronary Infarct

Using a genetic predisposition score (GPS), additively integrating the associations of 11 polymorphisms with coronary heart disease (CHD), we examined the consequences of the joint presence of a high GPS and nongenetic CHD risk factors. Within the European Prospective Investigation Into Cancer and Nutrition, 202 case patients with medically confirmed incident coronary infarct and 197 control subjects were identified in Greece. Each polymorphism contributed 1 unit (high-risk homozygous), one-half unit (heterozygous), or no units (low-risk homozygous) to the GPS. Odds ratios of coronary infarction for those at high risk because of genetic predisposition and simultaneous presence of an established CHD risk factor were estimated, compared with subjects at low risk, for both GPS and each CHD risk factor. The joint presence of a high GPS (> or =3.5) and each studied CHD risk factor was in all instances associated with a significantly increased risk of coronary infarction. The odds ratio (95% confidence interval) was 2.62 (1.14-6.02) for ever smoking, 2.88 (1.33-6.24) for hypertension, 3.50 (1.67-7.33) for low high-density lipoprotein (HDL) level, 3.05 (1.53-6.08) for high non-HDL level, and 3.66 (1.75-7.65) for poor adherence to the Mediterranean diet. The odds ratios were always lower and nonsignificant when the GPS was low. There was suggestive evidence for interaction of a high GPS with hypertension (P = .05) and non-HDL cholesterol level (P = .13). Genetic predisposition may interact with hypertension and, perhaps, also with the level of non-HDL cholesterol, in the causation of CHD. Genetic predisposition and the other studied exposures seem to have converging effects. Thus, the GPS may identify individuals who could realize disproportional benefits by controlling their hypertension and, possibly, their non-HDL cholesterol level.

CETP Genes, Metabolic Effects, and Coronary Disease Risk

THE BURDEN OF ATHEROSCLEROTIC CORONARY HEART disease (CHD) is tremendous—both genes and environment contribute to this problem. From a clinical perspective, physicians are well aware of the importance of genetic lipid abnormalities in the causation of CHD. The best studied genetic lipid abnormality is familial hypercholesterolemia (FH), which can cause clinical findings such as xanthomas, early atherosclerosis, and premature CHD. Approximately 1 out of 500 of the population are FH heterozygotes and 1 out of 1 000 000 are homozgotes. It has been estimated that FH accounts for approximately 6% of CHD on a population basis. The availability of widespread gene testing in population studies has turned the tables, and now it is possible to investigate the role of gene variants that initially do not manifest with clinical signs and symptoms. For example, apolipoprotein E4 variants are common and affect more than 20% of the population, and also are associated with higher low-density lipoprotein cholesterol (LDL-C) levels and increased CHD risk. It has been estimated that apolipoprotein E4 is responsible for approximately 11% of CHD in the population. In this issue of JAMA, Thompson and colleagues summarize information related to cholesteryl ester transfer protein (CETP) genotypes, CETP metabolic action, lipoprotein cholesterol levels, and CHD risk. Cholesteryl ester transfer protein is involved in intermediary cholesterol trafficking as an important regulator of reverse cholesterol transport. High-density lipoprotein (HDL) particles absorb cholesterol from the arterial wall, transfer this lipid to other plasma lipid particles via CETP, and the transferred cholesterol is subsequently delivered to the liver. There is great interest in developing pharmacological agents to favorably affect these mechanisms, up-regulate reverse cholesterol transport, and potentially reduce atherosclerosis via this pathway. The amount of information reviewed by Thompson et al is massive—their review includes data from more than 113 000 individuals across 92 studies. The authors provide summary analyses related to CETP genotype effects on biochemical phenotypes related to CETP metabolism, HDLcholesterol (HDL-C) level (a traditional risk factor for which the blood level is partly determined by CETP activity), and CHD risk estimates. The CETP genotype relationship to CHD risk reported by Thompson et al is similar to that reported in a metaanalysis that focused on the CETP TaqIB variants. The study by Thompson et al answers the call for a comprehensive analysis of the gene effects related to CETP, its metabolites, and CHD risk, and differs from previous analyses by including much more data, especially concerning the intermediate biomarkers related to CETP metabolism, and by providing information on CETP gene variants other than TaqIB. The authors also report that CETP variants are common and the alleles they investigate affect at least half of the population. As shown in Figure 2 in the article by Thompson et al, CETP gene variants were associated with a CETP mass that was typically reduced by approximately 6% to 10%, CETP activity was 6% to 9% lower, HDL-C levels ranged from 3% to 5% higher, apolipoprotein A-I levels were 1% to 2% lower, and triglycerides were typically 2% lower. The CETP gene variant associations were also associated with modestly favorable effects on LDL-C (0 to −2%) and apolipoprotein B (typically approximately −2%). The associations with LDL-C and apolipoprotein B might not have been anticipated because CETP is largely considered a facilitator of reverse cholesterol transport and gene variants of CETP would probably not be expected to be associated with favorable effects on other metabolic pathways. The authors demonstrate that genetic variants of CETP are relatively common—minor allele frequencies are −631C A (8%), −629C A (48%-52%), TaqIB (42%), I405V (35%-42%), and D442G ( 1%-3%). The associations between CETP mass and function are consistently in expected directions and would be anticipated to favorably affect HDL-C levels. Does this study change what clinicians should think about genes and CHD risk? This investigation broadens the field and shows that a genotype intimately related to HDL me-

Epidemiology and causation of coronary heart disease and stroke in India

Cardiovascular diseases are major causes of mortality and disease in the Indian subcontinent, causing more than 25% of deaths. It has been predicted that these diseases will increase rapidly in...

Should pediatric patients with hyperlipidemia receive drug therapy?

Hyperlipidemia is now established as a major risk factor for causation of coronary heart disease (CHD) in adults; however, there is much debate on the level of coronary risk at which lipid-lowering drugs should be used. These issues of possible harm or lack of benefit from long-term use of lipid-lowering therapy, and cost effectiveness, are also pertinent in the pediatric setting. Evidence from several countries indicates that children have an increasing prevalence of obesity, hyperlipidemia and type 2 diabetes mellitus. Children who have high serum lipids 'track' these increased levels into adulthood. In some countries there is a trend to screen children for hypercholesterolemia. Family history itself is a poor discriminator in determining which children need to be screened and treated. Estimation of apolipoprotein B and/or apolipoprotein E genotype can improve prediction. Measuring high density lipoprotein cholesterol also helps, but obesity appears to be the best marker for screening children at high risk. These considerations should not cloud the need for case finding and treatment of children with genetic disorders. Low fat diets have been shown to be well tolerated and effective in children; however, there are no major long-term studies demonstrating harm or benefit in those on lipid-lowering drugs. Nevertheless, concerns regarding the psychological effect and the theoretical metabolic effects of long-term lipid lowering remain. Lipid-lowering drugs should be generally restricted to children with genetic disorders of lipid metabolism. Children with diabetes mellitus, hypertension or nonlipid-related inherited disorders leading to premature CHD in adults should be treated with diet, and with lipid-lowering drugs when they reach adulthood. Children with secondary hyperlipidemia should be assessed individually. A number of drugs and nutriceuticals are available for use in children, but only a few drugs are licensed for use in children.

Dietary Fat: At the Heart of the Matter

The role of dietary fat in the causation of coronary heart disease (CHD) has long been a topic of interest and dispute. In his News Focus article, Gary Taubes discusses what he calls “The soft science of dietary fat” (30 Mar., p. [2536][1]). He reviews the history of the diet-heart issue and

Key role of dietary fats in coronary heart disease under progressive urbanization and nutritional transition

The increased vulnerability to non-communicable diseases (NCD) of developing populations experiencing a demographic and epidemiological transitions to increased risk of NCD at a time when the battle against infectious diseases, is ongoing. Apart from population growth, the major attributes of developmental transition are confined to changes in occupational pattern in family structure, lifestyle, dietary practices and progressive ageing of population. The emergence of the NCD is significantly associated with changes in dietary pattern, in most of the countries. Coronary heart disease (CHD) is the leading cause of death in developed countries and the incidence is increasing in developing countries, including India. The disease needs awareness of the risk factors responsible for prevention. The purpose of this review is to present an overview of the role of dietary fats in growth and development and in health and disease. Although the causation of CHD is multifaceted and the risk factors associated in general are several, there are specific and important elements, such as dietary fats and lifestyle. Dietary fats are an important component as they serve a number of functions in the body. The minimum desirable and upper limits of fat intake have been given, based on recommendations of expert groups. Sources of different fats are made available worldwide and the production, consumption, storage, oxidation and nomenclature are being discussed in the light of health and disease. The relative essentiality of the omega-6 and omega-3 fatty acids is recognized in terms of pharmacologically active eicosanoid metabolism. Nevertheless, epidemiological, physiological and clinical studies have demonstrated that long-chain omega-3 fatty acids present in fish oils have quite diverse health benefits. Appropriate guidelines need to be recommended at a national level consistent with dietary habits. The ratios of balanced fatty acids, namely omega-11, omega-9, omega-6 and omega-3, should be worked out appropriately in ameliorating nutrition-related disease states. Any simple dietary modification that can lead to a substantial reduction in morbidity and mortality from CHD would be of great medical, social and economic benefit.

Respiratory infection and coronary heart disease: progression of a paradigm.

We have developed a previously published paradigm concerning causation of coronary heart disease, based on the probability that the fundamental cause is a microbe, probably Chlamydia pneumoniae, and that the progress of the disease is influenced by number of accelerating and inhibiting factors. We propose that cigarette smoking acts via respiratory infection, this itself being influenced by immunocompetence resulting from sunlight exposure. We also propose an immuno-enhancing effect of oestrogen and an anti-inflammatory effect of statin therapy. In respect of the geographical variation of coronary heart disease, we emphasize that this must be viewed as part of the bigger picture of a high mortality from all causes in countries of North-west Europe that have a particularly low level of sunlight exposure. Finally, we draw attention to the Albanian, French, Italian, Northern Ireland and Scottish paradoxes which should lead to a major review of the conventional wisdom concerning the aetiogenesis of coronary heart disease.

Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies.

A large number of epidemiologic studies have reported on associations between various "inflammatory" factors and coronary heart disease (CHD). To assess the associations of blood levels of fibrinogen, C-reactive protein (CRP), and albumin and leukocyte count with the subsequent risk of CHD. Meta-analyses of any long-term prospective studies of CHD published before 1998 on any of these 4 factors. Studies were identified by MEDLINE searches, scanning of relevant reference lists, hand searching of cardiology, epidemiology, and other relevant journals, and discussions with authors of relevant reports. All relevant studies identified were included. The following information was abstracted from published reports (supplemented, in several cases, by the authors): size and type of cohort, mean age, mean duration of follow-up, assay methods, degree of adjustment for confounders, and relationship of CHD risk to the baseline assay results. For fibrinogen, with 4018 CHD cases in 18 studies, comparison of individuals in the top third with those in the bottom third of the baseline measurements yielded a combined risk ratio of 1.8 (95% confidence interval [CI], 1.6-2.0) associated with a difference in long-term usual mean fibrinogen levels of 2.9 pmol/L (0.1 g/dL) between the top and bottom thirds (10.3 vs 7.4 pmol/L [0.35 vs 0.25 g/dL]). For CRP, with 1053 CHD cases in 7 studies, the combined risk ratio of 1.7 (95% CI, 1.4-2.1) was associated with a difference of 1.4 mg/L (2.4 vs 1.0 mg/L). For albumin, with 3770 CHD cases in 8 studies, the combined risk ratio of 1.5 (95% CI, 1.3-1.7) was associated with a difference of 4 g/L (38 vs 42 g/L, ie, an inverse association). For leukocyte count, with 5337 CHD cases in the 7 largest studies, the combined risk ratio of 1.4 (95% CI, 1.3-1.5) was associated with a difference of 2.8 x 10(9)/L (8.4 vs 5.6 x 10(9)/L). Each of these overall results was highly significant (P<.0001). The published results from these prospective studies are remarkably consistent for each factor, indicating moderate but highly statistically significant associations with CHD. Hence, even though mechanisms that might account for these associations are not clear, further study of the relevance of these factors to the causation of CHD is warranted.

Coronary heart disease mortality trends in England and Wales, 1952–1991

The 'programming' hypothesis for the causation of heart disease suggests that there are critical periods of development in early life during which a stimulus or insult has permanent effects on the subject's organ or tissue structure and physiology. Exposure to such effects might be expected to be linked to year of birth and produce cohort (generation) effects in heart disease death rates. Evidence is sought for such effects in data from England and Wales.The age- and period-specific heart disease death rates for men and women aged 30-69 in England and Wales have declined recently in both men and women. The trends have two components. The first is described by a peak in rates during 1977-1981 that applies to both sexes and all age-groups. This is consistent with risk conferred by adult diet and lifestyle. The second component required to explain the trends also applies to both sexes and is described by a risk that is lower in each successive year of birth. This is consistent with risk linked to poor growth in early life.Poor early growth has become less common as maternal health, physique and nutritional status have improved through the century. The trends are therefore consistent with the'programming' hypothesis for the causation of coronary heart disease.

Dietary fats in the causation of coronary heart disease

University of New South Wales School of Medicine and Lipid Research Department, St Vincent's Hospital, Darlinghurst, New South Wales, Australia