EURO PEAN SO CIETY O F CARDIOLOGY ®
Original scientific paper
Quantifying the benefits of achieving or maintaining long-term low risk profile for cardiovascular disease: The Doetinchem Cohort Study
European Journal of Preventive Cardiology 2015, Vol. 22(10) 1307–1316 ! The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2047487314544083 ejpc.sagepub.com
Gerben Hulsegge1,2, Henrie¨tte A Smit2, Yvonne T van der Schouw2, Martha L Daviglus3,4 and WM Monique Verschuren1,2
Abstract Background: Studies investigating the relation between risk profiles and cardiovascular disease have measured risk at baseline only. We investigated maintenance and changes of risk profiles over time and their potential impact on incident cardiovascular disease. Design: Population-based cohort study. Methods: Risk factors were measured at baseline (1987–1991) among 5574 cardiovascular disease-free adults aged 20–59 years. They were classified into four risk categories according to smoking status, presence of diabetes and widely accepted cut-off values for blood pressure, total cholesterol/HDL-ratio and body mass index. Categories were subdivided (maintenance, deterioration, improvement) based on risk factor levels at six and 11 years of follow-up. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular disease incidence 5–10 years following the risk-change period were fitted using Cox proportional hazards models. Results: Only 12% of participants were low risk at baseline, and only 7% maintained it. Participants who maintained a low risk profile over 11 years had seven times lower risk of cardiovascular disease (HR: 0.14, 95% CI: 0.05–0.41) than participants with long-term high risk profile, whereas those low risk at baseline whose profile deteriorated had three times lower risk (HR: 0.36, 95% CI: 0.18–0.71). Our results suggest that, within each baseline risk profile group, compared with a stable profile, improving profiles may be associated with up to two-fold lower HRs, and deteriorating profiles with about two-fold higher HRs. Conclusions: Our study, using long-term risk profiles, demonstrates the full benefits of low risk profile. These findings underscore the importance of achieving and maintaining low risk from young adulthood onwards.
Keywords Cardiovascular disease, cohort study, risk factors, long-term, risk assessment Received 23 April 2014; accepted 30 June 2014
Introduction In past decades, research focused on the impact of elevated levels of the major cardiovascular disease (CVD) risk factors, that is, serum cholesterol, blood pressure, body mass index (BMI), smoking and diabetes. However, in most developed countries, the prevalence of major CVD risk factors remains high.1–3 As eloquently stated by Geoffrey Rose, the notion of what constitutes a healthy level for a risk factor is influenced by the mean population level of that risk factor.4
1 Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands 2 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands 3 Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, USA 4 Institute of Minority Health Research, University of Illinois at Chicago, USA
Corresponding author: Gerben Hulsegge, Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9, 3720 BA Bilthoven, The Netherlands. Email: [email protected]
Downloaded from cpr.sagepub.com at UNIVERSITE LAVAL on October 7, 2015
1308
European Journal of Preventive Cardiology 22(10)
From the perspective of optimal health and well-being, only a small proportion of the population has favourable levels of all major risk factors (i.e. a low risk profile) and an even smaller proportion maintains those low risk levels over time.5,6 Previous studies have demonstrated the benefits of having low levels of all major CVD risk factors. They have consistently demonstrated a significantly lower risk of coronary heart disease,7–10 stroke7,9,10 and total CVD7–9,11–13 at older ages among individuals who had low risk profile in young adulthood and middle-age compared with others. However, these earlier studies on benefits of low risk profile have relied on single measures of risk factors, obtained at baseline, without taking changes in risk profiles over time into account. The full impact of low levels of risk factors can only become apparent when looking at long-term low levels. In addition, the extent to which CVD risk differs between adults who maintain an unfavourable risk profile and those who experience improvement or deterioration in their risk profile over time is unknown, but risk profiles are likely to change and influence CVD risk. Therefore, in order to effectively demonstrate the importance of low risk and changes in risk profiles in CVD prevention, it is necessary to quantify the magnitude of the benefits of sustained low risk and the impact of changes in risk profiles over time. We investigated the association of baseline risk profiles with CVD risk and compared it with association of long-term risk profiles (sustained, improved or deteriorated over an 11-year period) with 5–10 year CVD risk following the risk change-period. This study is unique as we were able to use three repeated measurements of CVD risk factor over an 11-year period to define the long-term exposure of risk profiles and relate this to risk of CVD.
Methods Population The Doetinchem Cohort Study is an ongoing study involving an age- and sex-stratified random sample of men and women aged 20–59 years. They are drawn from the civil registries of Doetinchem, a town in the eastern part of the Netherlands with 46,967 inhabitants in the year 2000. At baseline (1987–1991: wave one), we invited 20,155 men and women to undergo a clinical examination. Of the 62% who participated (N ¼ 12,405), a random sample of 7768 participants was invited for a second examination (1993–1997: wave two) of whom 79% participated (N ¼ 6117). All participants invited to participate in wave two were also re-invited for a third examination (1998–2002: wave three) except for those who, at any point, did not give
permission to retrieve their information from the municipal administration, emigrated or otherwise withdrew from the study (n ¼ 1189). This resulted in the invitation of 6579 participants for wave three of whom 75% (N ¼ 4918) participated. Only participants who participated in two of the three waves were included (N ¼ 6368) in the analyses, of which 4661 participants attended all three examinations. The study design of the Doetinchem Cohort study has been described in detail elsewhere.14 All participants gave written informed consent and the study was approved according to the guidelines of the Helsinki Declaration by the external Medical Ethics Committee of the Netherlands Organization for Applied Scientific Research.
Measures The major CVD risk factors (i.e. weight and height to calculate BMI, diastolic and systolic blood pressure, total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol, and blood glucose) were measured by trained staff according to a standardized protocol. Lifestyle factors (i.e. physical activity, diet and alcohol intake), demographic characteristics and medical history were collected with standardized questionnaires. Details of these measurements have been described elsewhere14 and are available in the online Supplementary Material.
Definition of risk profile Baseline risk. Participants were categorized into four baseline risk profiles (low risk, medium-low risk, medium-high risk, and high risk) using smoking status, presence of diabetes and widely accepted cutoff values for blood pressure, TC/HDL-ratio and BMI as described in Table 1.7–11 The TC/HDL-ratio was used instead of TC as it has been associated more strongly with risk of CVD.15,16 Long-term risk. Each baseline risk profile was further categorised based on similarly defined risk-factor levels at six years (wave two) and 11 years (wave three) of follow-up, resulting in 11 distinct long-term risk profiles (Table 2): 1. Long-term low risk: favourable levels of all risk factors (i.e. low risk) at all three waves. Since only 154 participants were low risk at all waves, this profile also included persons low risk at two waves and medium-low risk at one. 2. Deteriorated low risk: low risk profile at baseline with worsening of risk profile during follow-up. 3–8. Medium-low or medium-high risk profile at baseline, with either maintenance of that profile at all
Downloaded from cpr.sagepub.com at UNIVERSITE LAVAL on October 7, 2015
History of diabetes
Former or never smoker 25.0-29.9 kg/m2
30.0 kg/m2
4.0–5.9 and not taking choles terol-lowering medication
6.0 and/or taking cholesterollowering medication
Currently smoking
Former or never smoker
Original scientific paper
Quantifying the benefits of achieving or maintaining long-term low risk profile for cardiovascular disease: The Doetinchem Cohort Study
European Journal of Preventive Cardiology 2015, Vol. 22(10) 1307–1316 ! The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2047487314544083 ejpc.sagepub.com
Gerben Hulsegge1,2, Henrie¨tte A Smit2, Yvonne T van der Schouw2, Martha L Daviglus3,4 and WM Monique Verschuren1,2
Abstract Background: Studies investigating the relation between risk profiles and cardiovascular disease have measured risk at baseline only. We investigated maintenance and changes of risk profiles over time and their potential impact on incident cardiovascular disease. Design: Population-based cohort study. Methods: Risk factors were measured at baseline (1987–1991) among 5574 cardiovascular disease-free adults aged 20–59 years. They were classified into four risk categories according to smoking status, presence of diabetes and widely accepted cut-off values for blood pressure, total cholesterol/HDL-ratio and body mass index. Categories were subdivided (maintenance, deterioration, improvement) based on risk factor levels at six and 11 years of follow-up. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular disease incidence 5–10 years following the risk-change period were fitted using Cox proportional hazards models. Results: Only 12% of participants were low risk at baseline, and only 7% maintained it. Participants who maintained a low risk profile over 11 years had seven times lower risk of cardiovascular disease (HR: 0.14, 95% CI: 0.05–0.41) than participants with long-term high risk profile, whereas those low risk at baseline whose profile deteriorated had three times lower risk (HR: 0.36, 95% CI: 0.18–0.71). Our results suggest that, within each baseline risk profile group, compared with a stable profile, improving profiles may be associated with up to two-fold lower HRs, and deteriorating profiles with about two-fold higher HRs. Conclusions: Our study, using long-term risk profiles, demonstrates the full benefits of low risk profile. These findings underscore the importance of achieving and maintaining low risk from young adulthood onwards.
Keywords Cardiovascular disease, cohort study, risk factors, long-term, risk assessment Received 23 April 2014; accepted 30 June 2014
Introduction In past decades, research focused on the impact of elevated levels of the major cardiovascular disease (CVD) risk factors, that is, serum cholesterol, blood pressure, body mass index (BMI), smoking and diabetes. However, in most developed countries, the prevalence of major CVD risk factors remains high.1–3 As eloquently stated by Geoffrey Rose, the notion of what constitutes a healthy level for a risk factor is influenced by the mean population level of that risk factor.4
1 Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands 2 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands 3 Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, USA 4 Institute of Minority Health Research, University of Illinois at Chicago, USA
Corresponding author: Gerben Hulsegge, Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Antonie van Leeuwenhoeklaan 9, 3720 BA Bilthoven, The Netherlands. Email: [email protected]
Downloaded from cpr.sagepub.com at UNIVERSITE LAVAL on October 7, 2015
1308
European Journal of Preventive Cardiology 22(10)
From the perspective of optimal health and well-being, only a small proportion of the population has favourable levels of all major risk factors (i.e. a low risk profile) and an even smaller proportion maintains those low risk levels over time.5,6 Previous studies have demonstrated the benefits of having low levels of all major CVD risk factors. They have consistently demonstrated a significantly lower risk of coronary heart disease,7–10 stroke7,9,10 and total CVD7–9,11–13 at older ages among individuals who had low risk profile in young adulthood and middle-age compared with others. However, these earlier studies on benefits of low risk profile have relied on single measures of risk factors, obtained at baseline, without taking changes in risk profiles over time into account. The full impact of low levels of risk factors can only become apparent when looking at long-term low levels. In addition, the extent to which CVD risk differs between adults who maintain an unfavourable risk profile and those who experience improvement or deterioration in their risk profile over time is unknown, but risk profiles are likely to change and influence CVD risk. Therefore, in order to effectively demonstrate the importance of low risk and changes in risk profiles in CVD prevention, it is necessary to quantify the magnitude of the benefits of sustained low risk and the impact of changes in risk profiles over time. We investigated the association of baseline risk profiles with CVD risk and compared it with association of long-term risk profiles (sustained, improved or deteriorated over an 11-year period) with 5–10 year CVD risk following the risk change-period. This study is unique as we were able to use three repeated measurements of CVD risk factor over an 11-year period to define the long-term exposure of risk profiles and relate this to risk of CVD.
Methods Population The Doetinchem Cohort Study is an ongoing study involving an age- and sex-stratified random sample of men and women aged 20–59 years. They are drawn from the civil registries of Doetinchem, a town in the eastern part of the Netherlands with 46,967 inhabitants in the year 2000. At baseline (1987–1991: wave one), we invited 20,155 men and women to undergo a clinical examination. Of the 62% who participated (N ¼ 12,405), a random sample of 7768 participants was invited for a second examination (1993–1997: wave two) of whom 79% participated (N ¼ 6117). All participants invited to participate in wave two were also re-invited for a third examination (1998–2002: wave three) except for those who, at any point, did not give
permission to retrieve their information from the municipal administration, emigrated or otherwise withdrew from the study (n ¼ 1189). This resulted in the invitation of 6579 participants for wave three of whom 75% (N ¼ 4918) participated. Only participants who participated in two of the three waves were included (N ¼ 6368) in the analyses, of which 4661 participants attended all three examinations. The study design of the Doetinchem Cohort study has been described in detail elsewhere.14 All participants gave written informed consent and the study was approved according to the guidelines of the Helsinki Declaration by the external Medical Ethics Committee of the Netherlands Organization for Applied Scientific Research.
Measures The major CVD risk factors (i.e. weight and height to calculate BMI, diastolic and systolic blood pressure, total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol, and blood glucose) were measured by trained staff according to a standardized protocol. Lifestyle factors (i.e. physical activity, diet and alcohol intake), demographic characteristics and medical history were collected with standardized questionnaires. Details of these measurements have been described elsewhere14 and are available in the online Supplementary Material.
Definition of risk profile Baseline risk. Participants were categorized into four baseline risk profiles (low risk, medium-low risk, medium-high risk, and high risk) using smoking status, presence of diabetes and widely accepted cutoff values for blood pressure, TC/HDL-ratio and BMI as described in Table 1.7–11 The TC/HDL-ratio was used instead of TC as it has been associated more strongly with risk of CVD.15,16 Long-term risk. Each baseline risk profile was further categorised based on similarly defined risk-factor levels at six years (wave two) and 11 years (wave three) of follow-up, resulting in 11 distinct long-term risk profiles (Table 2): 1. Long-term low risk: favourable levels of all risk factors (i.e. low risk) at all three waves. Since only 154 participants were low risk at all waves, this profile also included persons low risk at two waves and medium-low risk at one. 2. Deteriorated low risk: low risk profile at baseline with worsening of risk profile during follow-up. 3–8. Medium-low or medium-high risk profile at baseline, with either maintenance of that profile at all
Downloaded from cpr.sagepub.com at UNIVERSITE LAVAL on October 7, 2015
History of diabetes
Former or never smoker 25.0-29.9 kg/m2
30.0 kg/m2
4.0–5.9 and not taking choles terol-lowering medication
6.0 and/or taking cholesterollowering medication
Currently smoking
Former or never smoker
