Body Mass Index and Initial Presentations of Cardiovascular Diseases (CALIBER)

The association between obesity and cardiovascular disease (CVD) has mostly been studied using broad endpoints or have focused on cause-specific mortality. The investigators aim to compare the effect of body mass index (BMI) on different types of initial presentation of CVD.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Stroke; Peripheral Arterial Disease; Acute Myocardial Infarction; Abdominal Aortic Aneurysm; Angina

Detailed Description

Obesity has many detrimental effects on the cardiovascular system that can manifest in a range of clinical presentations. Many of these are mediated by frequently coexisting conditions such as diabetes, hypertension and dyslipidemia but there are also direct, progressive effects on the arteries and the heart muscle. As evident from autopsies, even from early adulthood the degree of coronary artery disease (CAD) correlates with the BMI and particularly the amount of abdominal fat. The multiple mechanisms by which obesity exerts its effects are still being elucidated.

Previous studies have assessed the effect of obesity on cause-specific mortality. Here the investigators analyze association of BMI with the first symptomatic presentation of cardiovascular disease across any phenotypes, to which the investigators refer to as "initial presentation" to distinguish from first presentation within a specific phenotype. For example, an initial presentation with myocardial infarction is an MI which is not preceded by stable angina, ischemic stroke or any other phenotype, rather than the first MI in a possible series of MIs, as is commonly used in other studies.

Adjustments The key risk factor of interest is baseline BMI, which the investigators define as the most recent measurement of BMI recorded up to 2 years prior to cohort entry date. BMI will be analyzed based on the following categories: underweight (<18.5 kg/m2), healthy (18.5 to 24 kg/m2), overweight (25 to 29 kg/m2), moderately obese (30 to 34 kg/m2), morbidly obese (>35 kg/m2). The healthy BMI category will be used as the reference in regression models.

Associations with BMI will be adjusted for age, sex, ethnicity, social deprivation, smoking, diabetes, and systolic blood pressure, total cholesterol (TCHOL) and high-density lipoprotein cholesterol (HDL). All baseline covariates will be obtained from within a 2 year window prior to study entry.

Statistical analyses Cause-specific Cox models will be used to measure the association between BMI categories and endpoints of interest. Multiple imputation will be used to replace missing values in prognostic factors. The investigators will estimate lifetime risk for each endpoint over time adjusting for competing risks.

• Study Type: Observational
• Enrollment (Actual): 2240000

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, WC1E 6BT
    • University College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The cohort we will use in the present analysis has been drawn from patients across 225 practices in England contributing data to GPRD, covering approximately 5% of the UK population (Figure 1). The study period is 1st January 2001 to 25th March 2010 (the date of the last GPRD data submission). To allow time for medical history and risk factors to be measured and recorded we require that patients enter the cohort after having completed at least 1 year of registration with their current practice during which the practice provides data that meet research quality criteria. Patients are followed up from the date they become eligible to be included in the cohort until the earliest date among a) the date of an initial presentation with one of the endpoints of interest, b) the date of leaving the practice or c) the date of last data submission from their practice.

Description

Inclusion Criteria:

• Baseline age ≥30 years

Exclusion Criteria:

• prior atherosclerotic disease or stroke

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

CALIBER Healthy Cohort; We will report findings from the CALIBER (CArdiovascular disease research using Linked BEspoke studies and Electronic Records) collaboration where we linked primary care data (from the General Practice Research Database [GPRD]) to three further sources of electronic health records: the Myocardial Ischemia National Audit Project registry (MINAP),cause specific discharge data from Hospital Episodes Statistics (HES) and cause specific mortality from the Office for National Statistics (ONS).

Collaborators and Investigators

• Sponsor: University College, London

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: October 8, 2012
• First Submitted That Met QC Criteria: October 10, 2012
• First Posted (Estimate): October 11, 2012

Study Record Updates

• Last Update Posted (Estimate): October 11, 2012
• Last Update Submitted That Met QC Criteria: October 10, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Acute Myocardial Infarction; Peripheral arterial disease; Heart failure; Coronary heart disease not otherwise specified; Unstable angina; Stable angina; Abdominal aortic aneurysm; Transient Ischemic Attack; Haemorrhagic stroke; Ischaemic stroke; Unheralded coronary death; Ventricular arrhythmias, cardiac arrest and sudden cardiac death
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Aortic Diseases; Myocardial Infarction; Infarction; Heart Failure; Cardiovascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal
• Other Study ID Numbers: CALIBER 10_14