Abstract

The NHLBI Family Heart Study is a multi-center population-based study of genetic and non-genetic determinants of coronary heart disease (CHD), artherosclerosis, and cardiovascular risk factors. In Phase I 2,000 randomly selected participants and 2,000 with family histories of CHD were identified among 14,592 middle-aged participants in epidemiological studies. Medical histories from these individuals, their parents and siblings were used to calculate family risk scores which compared the number of reported and validated CHD events with the number expected based on the size, sex and age of family members. A total of 661 families with the highest risk scores and early onset of CHD and 592 randomly sampled families had clinic examinations including electrocardiograms, carotid artery ultrasound scans, spirometry, measurements of body size, blood pressure, lipids, lipoproteins, hemostatic factors, insulin, glucose, and routine chemistries. Additional biochemical and genetic studies are being done on selected participants. Serum, plasma, lymphocytes, red cells and DNA are stored for future studies, including genotyping of candidate genes and anonymous markers. Contributions of genes, shared and individual environments, and behaviors to variation in risk factors, preclinical atherosclerosis and CHD will be estimated. Linkage studies, including the quantitative trait loci approach are planned.

1. Key words: coronary heart disease, epidemiology, genetics, hypertension, risk factors

In summary, existing information on 14,592 participants in ongoing epidemiological studies was used to identify 2,000 randomly selected individuals (approximately 500 at each site) and approximately 2,000 individuals with high family risk scores (approximately 500 at each site). These individuals and all 485 black participants in North Carolina were asked to participate in Phase I of the Family Heart Study by providing family histories, names and addresses of their relatives and medical histories for themselves. Approximately 25,000 relatives were subsequently asked to provide their own medical histories of CHD and related conditions. The numbers of probands and relatives who responded are shown in table 1 together with response rates at each site. Data are available in Phase I for 67 percent of probands and 86 percent of their relatives. Response rates were lowest for the black population (41 percent for probands and 59 percent for relatives) and highest for the white population in Framingham (82 percent for probands) and Minneapolis (94 percent for relatives). Because of the low response rate and the paucity of families with CHD affected living members in the black population, Phase I activities are continuing and being expanded to recruit high risk black families from a clinic and local hospitals.

Phase II (February 1994 - December 1995)

In Phase II, adult members of 592 randomly selected families and 661 families with the highest risk scores were recruited for clinical examination and follow up (table 2). Selection of high risk families were based on the number of CHD events, as well as the recomputed family risk score, using validated events. Families with two or more CHD events and risk scores of 0.5 or higher were considered to be eligible. Family members aged 25 or older were offered clinic examinations provided that at least 50% of the eligible members, including at least two biologically related individuals, returned personal medical histories. Random sample families were invited to clinic examinations using the same age and response criteria, but without regard to history of CHD. Eligibility criteria for black families were relaxed so that any two biologically variables.

Final numbers of examined individuals and families and response rates are shown in table 2. A total of 5,348 members of 1,253 families completed the extensive clinic examination and another 627 individuals provided medical histories and blood samples at remote sites.

Annual follow-up of examined participants was designed to maintain contact and to update information on CHD events, hospitalizations for related conditions, and deaths from all causes.

Quality assurance and quality control

The protocol was detailed in a set of nine manuals of procedure which specify the equipment, conditions, preparation, and handling of the subjects and samples (6). The Office of Management and Budget approved the study design, procedures, and forms. A pilot study tested all aspects of the data collection and data flow procedures through the Field, and Reading Centers and Core Laboratory to the Coordinating Center. An independent NHLBI appointed Monitoring Board reviewed and approved the plans and readiness of the agencies to conduct the study before data collection began, and regularly reviews progress.

Quality assurance and quality control of the data was accomplished through training and certification of technicians, calibration and servicing of equipment and logs of performance. The Coordinating Center prepared reports on the study progress and highlighted potential problems for the Steering Committee which made decisions regarding study conduct and protocol changes. Subcommittees on Examinations, Quality Control, Event Validation, and Publications monitor progress and make recommendations to the Steering Committee. Study coordinators and data managers at each site resolve day to day operational problems, and assure that centers continue to operate consistently.

Monitoring visits were made to each Field Center, the Coordinating Center, the Central Blood Chemistry Laboratory, the Ultrasound Reading Center, Pulmonary Function Reading Center, and the ECG Reading Center.

Table 1. NHLBI1 Family Heart Study family and medical histories 1993-1995

 

Pre-phase I

Phase I

   

Random

High risk

Total

Response rates

Field Center

Potential probands

Proband

Relatives

Proband

Relatives

Proband

Relatives

Proband

Relatives

Forsyth County

4,034

527

2,889

352

2,231

887

5,131

55.4

73.6

White

3,549

325

1,007

352

3,231

675

4,122

62.9

78.3

Black

521

202

1,002

---

---

212

1,009

41.0

58.8

Minneapolis

3,941

385

2,863

433

3,548

818

6,411

75.3

93.7

Framingham

2,650

414

2,445

398

2,794

810

5,239

82.0

86.0

Salt Lake City

3,967

318

2,799

329

3,340

635

6,127

63.9

90.1

Total

14,592

1,644

10,996

1,512

11,913

3,150

22,909

67.0

85.8

1National Heart, Lung, and Blood Institute

Table 2. NHLBI Family Heart Study 1994-1995 Phase II--clinic examinations

 

Random

High CHD risk

Total

Field Center

Families

Individuals

Families

Individuals

Families

Individuals

Forsyth County

200

595

197

696

397

1,291

White

149

477

146

543

295

1,031

Black1

51

109

51

153

102

262

Minneapolis

118

545

194

850

312

1,395

Framingham

149

582

150

594

299

1,176

Salt Lake City

126

796

120

690

245

1,486

Total

592

2,518

661

2,830

1,253

5,348

1See text for CHD risk classification.
An addtional 627 remote-site exams were completed