Emerging Risk Factors (A4, A11, A12)

Lead Research Organisation: Medical Research Council

Abstract

A4. PROCARDIS (Precocious Coronary Artery Disease) It aims to identify undiscovered susceptibility genes for coronary heart disease. It is a study of 2600 pairs of siblings both with coronary heart disease, plus other relevant family members for genetic analysis, and a case-control study involving 4653 genetically-enriched cases and 5188 disease-free unrelated controls. It is expected to lead to new approaches to diagnosis, prevention or treatment of vascular disease. A11: Whitehall prospective study in older people (and collaborative meta-analyses of emerging risk factors) A prospective re-survey of over 5000 older men and meta-analyses of prospective studies of emerging risk factors). It aims to quantify the relevance of blood lipids, inflammatory markers and genetic markers for mortality in older people. A12. Meta-analyses of observational and intervention studies of homocysteine and vascular disease Meta-analysis of observational studies of homocysteine; and meta-analyses of randomised trials of the lowering of homocysteine with folic acid based supplements and the risks of clinical events. It aims to determine age-specific risks of cardiovascular disease associated with prolonged differences in blood homocysteine concentrations, and to explore the effects of vitamin supplementation with folic acid based therapy on cardiovascular disease. It should provide reliable evidence about the effects of lowering homocysteine on the risk of vascular and non-vascular outcomes.

Technical Summary

A1 A4. PROCARDIS (Precocious Coronary Artery Disease) Objectives: to identify undiscovered susceptibility genes for coronary heart disease (CHD). Design: study of 2600 pairs of siblings both with CHD; association studies of 1300 patients with CHD and parental or unaffected sibling controls; and case-control studies involving 4653 genetically-enriched CHD cases and 5188 disease-free unrelated controls. Techniques: genome-wide linkage screen, fine mapping of regions of linkage using intra-family association studies and genome-wide association studies in genetically-enriched cases and controls. Measurements: Blood pressure, height and weight and information about smoking, alcohol consumption, medical history and medication. Anticipated implications: new approaches to diagnosis, prevention or treatment of vascular disease. A11: Whitehall prospective study in older people (and collaborative meta-analyses of emerging risk factors) Objectives: To quantify the relevance of blood lipids, inflammatory markers and genetic markers for mortality in older people. Design: Prospective re-survey of over 5000 older men (and meta-analyses of prospective studies of emerging risk factors). Techniques: Questionnaires from 7044 surviving participants in the Whitehall study, first surveyed in 1970; measurements of blood pressure, height and weight; blood samples from 5434 men; medical history, medication use, and mortality follow-up status for 5360 of these men. Measurements: Questionnaire details of medical diagnoses (angina, heart attack or diabetes), medications, smoking status and last known employment grade. Plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B, and apolipoprotein A1, C-reactive protein (CRP), fibrinogen, albumin, cystatin C, anti-oxidant vitamins and fatty acids. A12. Meta-analyses of observational and intervention studies of homocysteine and vascular disease Objectives: To determine the age-specific risks of cardiovascular disease associated with prolonged differences in usual blood homocysteine concentrations, and to explore the possible effects of vitamin supplementation with folic acid based therapy on cardiovascular disease. Design: Meta-analysis of observational studies of homocysteine (Homocysteine Studies Collaboration); and meta-analyses of randomised trials of the lowering of homocysteine with folic acid based supplements (Homocysteine Lowering Trialists collaboration) and the risks of clinical events (B-Vitamin Treatment Trialists collaboration). Techniques: Data from 55 observational studies of blood homocysteine levels and vascular disease (16,786 individuals), and randomised trials of the effects of folic acid on homocysteine (2600 people). Data will be collected on each of the 52,000 participants in the 12 large-scale trials of B vitamin supplementation for prevention of vascular disease. Measurements: data from epidemiological studies on smoking, blood pressure and the plasma levels of homocysteine, folate, vitamin B12 and cholesterol; from trials with biochemical endpoints, data on homocysteine, folate and vitamin B12 concentrations before and after treatment; from trials on clinical outcomes, data to allow analyses of the effects on cause-specific mortality, heart attacks, strokes, venous thromboembolic events, cancers and fractures. Anticipated implications: reliable evidence about the effects of interventions that lower homocysteine on the risk of vascular and non-vascular outcomes. A4. PROCARDIS (Precocious Coronary Artery Disease) It aims to identify undiscovered susceptibility genes for coronary heart disease. It is a study of 2600 pairs of siblings both with coronary heart disease, plus other relevant family members for genetic analysis, and a case-control study involving 4653 genetically-enriched cases and 5188 disease-free unrelated controls. It is expected to lead to new approaches to diagnosis, prevention or treatment of vascular disease. A11: Whitehall prosp

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