The Copenhagen City Heart Study (Østerbroundersøgelsen)

Abstract

The Copenhagen City Heart Study, also known as "Østerbroundersøgelsen", is a large prospective cardio-vascular population study of 20,000 women and men that was launched in 1975 by Dr Peter Schnohr and Dr Gorm Jensen together with statistician Jørgen Nyboe and Prof. A. Tybjærg Hansen. The original purpose of the study was to focus on prevention of coronary heart disease and stroke. During the years many other aspects have been added to the study: pulmonary diseases, heart failure, arrhythmia, alcohol, arthrosis, eye diseases, allergy, epilepsia, dementia, stress, vital exhaustion, social network, sleep-apnoe, ageing and genetics. In this review we highlight unique aspects of the Copenhagen City Heat Study (CCHS) and its outcome in investigations of clinical and molecular aspects of health and disease in the regional and global population. To increase the impact of population studies with a focus on risk and prevention of cardiovascular and related diseases and to maximize the likelihood of identifying disease causes and effective therapeutics, lessons learned from past research should be applied to the design, implementation and interpretation of future studies.

Figure 1.

CCHS Study area and participating Hospitals. Since a reform in 2006–08, Copenhagen Municipality has been divided into 10 official districts Indre By, Østerbro, Nørrebro, Vesterbro/Kongens Enghave, Valby, Vanløse, Frederigsberg, Brønshøj-Husum, Bispebjerg, Amager Øst, and Amager Vest. The primary population was a random sample of almost 20,000 men and women 20 – 93 years old, drawn from a population of approximately 90,000 inhabitants aged 20 years or older living within 10 wards (the entire of Østerbro and 1/3 of Nørrebro) surrounding Rigshospitalet, Copenhagen. The study was based at Rigshospitalet from 1975 to 1997. From 1997, the Copenhagen City Heart Study has been based at Bispebjerg University Hospital, where the fourth survey was performed in 2001–2003. The Copenhagen City Population study (a sister study) is based in a suburb of Copenhagen named Herlev in the Herlev Hospital, a Copenhagen University Hospital.

Figure 2.

Study population: invited and examined. The total number of participants invited to the first four examinations was: 19,329+500+3,000+1,062 = 23,891 men and women. Of the original 14,223 examined at the first examination 3,092 (21.7%) have been examined in all four examinations, and of the 5,106 non-responders from the first survey in 1976–1978, 1,698 responded and were examined in one or more of the following surveys.

Figure 3.

Examinations were performed at three different workplaces, each lasting 6–8 minutes per station per person examined. At the end of the examination the participant was asked to contact the general practitioner after two weeks (or earlier in case of any abnormal findings) to receive results of the blood sample analyses.

Figure 4.

The CCHS provides a strong background for numerous sub-studies. If a participant was eligible for any of the sub-studies, the procedure was started after his acceptance.

Figure 5.

All-cause mortality HRs, adjusted for age and sex and multivariable adjusted for joggers compared with sedentary nonjoggers. Jogging variables: Quantity, frequency, and pace of jogging in relation to all-cause mortality. HR = hazard ratio. *p <  0.10; **p <  0.05; ***p <  0.01; ****p <  0.001. From: Schnohr et al., 2015, http://dx.doi.org/10.1016/j.jacc.2014.11.023.

Figure 6.

Dose of jogging and long-term mortality. Forest plot indicating all-cause mortality in light, moderate, and strenuous joggers compared with sedentary nonjoggers. From: Schnohr et al. JACC. 2015, http://dx.doi.org/10.1016/j.jacc.2014.11.023.

Figure 7.

Upper panel: Berlingske, one of the most renowned and best-selling Danish national daily newspaper (based in Copenhagen) published an article in 2013 with a photo showing Dr. Schnohr jogging. The articles title: The Man who ran ahead. The figure's caption: Peter Schnohr, cardiologist and the man behind Eremitageløbet (a jogging competition held in the deer park north of Copenhagen each year in early October), today 70 years old, still jogs twice a week around the lakes in Copenhagen. With the large population study, The Copenhagen City Heart Study, he and his team show that jogging prolongs life. Lower panel: An article published by The Telegraph (UK) in early 2015 entitled “Fast running is as deadly as sitting on couch, scientists find”.

Figure 8.

Biochemical signs of liver damage according to alcohol intake in the general population. Values are from the 2001–2003 examination of the Copenhagen City Heart Study. Average values shown are estimated from generalized linear models and apply for a reference person (age 40 years, never smoker, and education less than or equal to7 years). P values are for linear trend. ALT, alanine aminotransferase, γ-GT, γ-glutamyl transpeptidase. From: Tolstrup et al. 2009. doi: 10.1038/ajg.2009.370.

Figure 9.

Absolute 10-year risk of MI (A) and by lipoprotein(a) levels, gender, smoking, hypertension, and age. Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation. 10.1161/circulationaha.107.715698.

Figure 10.

Association between the nonsynonymous TM6SF2 variant (p.Glu167Lys), liver enzymes and plasma lipid levels in DHS, the Dallas Biobank and the Copenhagen Study. Values are means ± s.d. Association was tested using linear regression with adjustment for age, sex, BMI and ancestry (where appropriate). A logarithm transformation was applied to traits with non-normal distributions. AST was only measured in a subset of the Copenhagen Study (n = 8,487). Ancestry breakdown for DHS is provided in Supplementary Table 3.ALT, alanine aminotransferase; AST, aspartate transaminase; ALP, alkaline phosphatase; LDL-C, low-density lipoprotein–cholesterol. ^aEE, homozygotes for the allele encoding Glu167; EK, heterozygotes; KK, homozygotes for the allele encoding Lys167. From: Kozlitina et al., Nat Genet. 2014, 46(4):352-6. doi: 10.1038/ng.2901.

Figure 11.

Mean plasma levels of nonfasting triglycerides and hazard rations for ischemic vascular disease and ischemic heart disease as a function of APOC3 genotype. Data are for all heterozygotes for the R19X, IVS2+1G → A, or A43T mutation versus noncarriers of these mutations among participants in the CCHS and the CGPS combined. The median follow-up period was 34 years. The theoretically predicted risk ratios were calculated as the risk of ischemic vascular disease or ischemic heart disease associated with a decrease in levels of nonfasting triglycerides among all heterozygotes as compared with noncarriers. P values are for the association between genotype and the observed risk of ischemic vascular disease or ischemic heart disease. The analyses were adjusted for age (as the time scale), sex, current smoking status, presence or absence of hypertension, physical inactivity, and alcohol consumption. From: Jørgensen et al., N Engl J Med. 2014 Jul 3;371(1):32–41. doi: 10.1056/NEJMoa1308027.