RESEARCH ARTICLE
The longitudinal associations between C-reactive protein and depressive symptoms: evidence from the English Longitudinal Study of Ageing (ELSA) Bonnie Au1,2, Kimberley J. Smith2,3, Geneviève Gariépy1,2 and Norbert Schmitz1,2,3,4 1
Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada Douglas Mental Health University Institute, Montreal, Quebec, Canada 3 Department of Psychiatry, McGill University, Montreal, Quebec, Canada 4 Montreal Diabetes Research Center, Montreal, Quebec, Canada Correspondence to: B. Au, E-mail: [email protected] 2
Objectives: The inflammatory marker C-reactive protein (CRP) is associated with depression. We exam-
ined the directional relations between CRP and symptoms of depression among older adults. Method: The sample consisted of 3397 participants from the English Longitudinal Study of Ageing, a prospective study of community-dwelling older adults. CRP and depressive symptoms were measured at baseline and follow-up. A high CRP level was dichotomized as >3 mg/L. Elevated depressive symptomatology was defined as ≥4 using the 8-item Center for Epidemiologic Studies Depression Scale. Logistic regressions computed the association between high CRP levels at baseline with elevated depressive symptoms at follow-up, and vice versa. Results: After adjusting for baseline depressive symptoms, baseline high CRP levels were associated with subsequent elevated symptoms of depression (OR = 1.49; 95% CI, 1.19–1.88). This relationship was no longer significant after simultaneous adjustments for metabolic and health variables. In the other direction, after adjusting for baseline CRP levels, baseline elevated depressive symptoms was not associated with subsequent high CRP levels (OR = 1.12; 95% CI, 0.88–1.42). Conclusion: High CRP levels at baseline are related to elevated depressive symptomatology at follow-up due to clinical factors. No association was found in the opposite direction. Copyright # 2014 John Wiley & Sons, Ltd. Key words: depression; inflammation; C-reactive protein; older adults; longitudinal History: Received 20 June 2014; Accepted 18 November 2014; Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/gps.4250
Introduction The older population is the fastest growing age group in the world as a result of longer life expectancy, declining fertility rate, and a shift from infectious to chronic non-communicable diseases as prevailing causes of disability and death (Aging, 2007; Currie, 2013). Depression among older adults is a growing public health concern worldwide (Ustun et al., 2004). Over a third of the population in England is comprised of older adults aged ≥50 years (Statistics, 2013), and the prevalence of depressive symptoms is Copyright # 2014 John Wiley & Sons, Ltd.
estimated at more than 17% among communitydwelling English older adults (Zivin et al., 2010). Depressive symptoms adversely affect the quality of life of older persons in terms of functioning and wellbeing (Penninx et al., 1998), and increase the risks of morbidity and mortality (Lee et al., 2001; Fiske et al., 2009). However, the pathophysiology of depression remains elusive among older adults. Consideration of biological risk factors for depression is important in older age because depression often arises in co-morbidity with chronic medical conditions (Alexopoulos, 2005). These medical
Int J Geriatr Psychiatry 2014
B. Au et al.
conditions are associated with changes in endocrine, cardiovascular, and inflammatory risk factors (Fiske et al., 2009). Given the disease-related processes involved in older ages, it is possible that dysregulation in these biological pathways could be involved in the etiology of depression (Alexopoulos, 2005; Fiske et al., 2009). One biological theory of depression that incorporates disease-relevant pathways is the cytokine hypothesis of depression (Ito and Ikeda, 2003), which posits that increased inflammation is involved in the pathophysiology of depression (Dantzer et al., 2008). Inflammatory markers that are speculated in the biological etiology of depression include interleukin-6 (IL-6) and its ensuing acute phase response C-reactive protein (CRP) (Silić et al., 2012). CRP is a wellestablished marker for inflammation and is gaining increasing attention for its role in the pathophysiology of depression (Howren et al., 2009; Penninx et al., 2013). Prospective data from aging cohorts are needed to ascertain whether inflammation is a cause or consequence of depression. There is a scarcity of studies that have examined the longitudinal relationship between CRP and depressive symptoms among older adults. Results from these studies have been mixed, with some studies finding a prospective association between CRP and incident depression (van den Biggelaar et al., 2007; Luukinen et al., 2010) and others finding no association (Forti et al., 2010; Baune et al., 2012). A recent review using only longitudinal studies found a small association between raised CRP levels with subsequent development of depressive symptoms (Valkanova et al., 2013). However, the meta-analysis consisted of only three studies which assessed the association specifically among older adults, and all three studies analyzed CRP as the baseline exposure and depression as the follow-up outcome which limits inferences on the directionality of the CRP and depression relationship. Only one study has examined the directional relations between CRP and depression among older adults (Stewart et al., 2009), and evidence of weak directional relationships between depressive symptoms and CRP were observed, but neither of the associations was statistically significant. However, the study conducted by Stewart et al. (2009) was limited to a small sample size of 263 healthy volunteers, which may not be representative of a general population of older adults and an underestimation of effects is possible. Furthermore, depressive symptoms and CRP levels were analyzed continuously, which may limit clinical interpretation with regards to defining a caseness for having elevated depressive symptomatology or low-grade inflammation. We aim to add to this area of research by Copyright # 2014 John Wiley & Sons, Ltd.
investigating the associations in a larger representative community-dwelling sample of older adults and analyzing depressive symptoms and CRP levels based on established cut-offs. The main objective of this study is to assess the directional relationship between CRP and depression to determine (a) whether having high CRP level at baseline is associated with occurrence of elevated depressive symptoms at follow-up and (b) whether having elevated depressive symptoms at baseline is associated with high CRP level at follow-up from the English Longitudinal Study of Ageing (ELSA), a prospective study of community-dwelling English older adults. A secondary objective is to evaluate the role of covariates such as socio-demographics, health behaviors, metabolic factors, and heath conditions in the CRP–depression relationship. Methods Design/setting and participants
ELSA is a nationally representative cohort study of older English adults living in households. ELSA consists of men and women born on or before 29 February 1952. The sample was derived from households that had participated in the Health Survey for England (HSE) in 1998, 1999, and 2001. The HSE recruited participants using multistage stratified probability sampling with postcode sectors selected at the first stage and household addresses selected at the second stage. For the present analyses, data from wave 2 (2004–2005) were used as baseline since this was the first occasion when clinical assessments including blood samples were collected by a nurse. Wave 4 (2008–2009) was used as the follow-up since it contains data on both clinical measures (every four years) and depressive symptoms (every two years). Participants provided full informed written consent, and ethical approval was granted by the London Multi-centre Research Ethics Committee. A total of 9432 participants attended the wave 2 core assessment. The present study reports only on participants who consented and were able to give blood (n = 7666) in wave 2 clinical assessment. Missing biological data was mainly because participants did not consent to give blood or were ineligible (people with clotting/bleeding disorders or taking anti-coagulant medication). After excluding participants that did not attend the core and clinical assessments at wave 4 (n = 2506), did not have valid baseline or follow-up CRP measurement (n = 1746), and had missing Int J Geriatr Psychiatry 2014
C-reactive protein and depressive symptoms
baseline or follow-up CES-D score (n = 17), the final analytic sample comprises of 3397 individuals. Compared to the baseline cohort, the analytical sample was slightly younger (64.6 vs. 65.8 years), more likely to be employed (35.8% vs. 24.4%) and involved in high levels of physical activity (23.0% vs. 18.8%). They also had a lower prevalence of diabetes (6.2% vs. 30.2%), cardiovascular conditions (19.5% vs. 43.0%), arthritis (36.4% vs. 52.0%) and asthma (12.8% vs. 33.5%).
Socio-demographic variables. Demographic vari-
ables included age, sex, and marital status (married, single never married, divorced/separated, or widowed). Education was assessed by asking participants to report their highest attained educational qualification (university degree or equivalent, less than university degree, or no qualification). Additional socio-demographic variable included working status (employed, unemployed, or retired). Ethnicity was not included because 99% of the sample was white. Health behaviors. Health-related behaviors included
Measures Depressive symptoms. Symptoms of depression were
assessed using the 8-item Centre of Epidemiological Studies Depression (CES-D) scale (Radloff, 1977; Missinne et al., 2014). Participants responded, yes or no, to items of depressive symptoms including depressed mood, restless sleep, decreased energy, and enjoyment in life, as well as feelings of loneliness and sadness. Symptoms of depression were dichotomized into low (CES-D 3 mg/L) levels. This cut-off value for CRP was based on clinical guidelines from the Centers for Disease Control and Prevention and American Heart Association that concentrations of CRP above 3 mg/L be used to indicate high risk of cardiovascular diseases (Pearson et al., 2003). Furthermore, CRP levels above this concentration have been defined as low-grade inflammation (Das, 2011; Barberato et al., 2013; Sorensen et al., 2014). This classification has also been used in previous studies with depression (Almeida et al., 2007; Almeida et al., 2009). Covariates. We identified potentially relevant socio-
demographic, lifestyle, and clinical contributors in the link between inflammation and depression based on recommendations from a review by O’Connor et al. (2009). Copyright # 2014 John Wiley & Sons, Ltd.
baseline smoking status (smoker or non-smoker) and physical activity. Physical activity was a derived variable based on the combination of occupational and leisure activities that was classified using the Allied Dunbar Survey of Fitness (1992). Level of physical activity was dichotomized into high physical activity versus not high physical activity (i.e. sedentarymoderate). Metabolic measures. Nurses collected anthropometric data (height and weight) and blood samples at both waves. Body mass index (BMI) was derived from weight and height based on the standard formula (kg/m2). Blood samples were also analyzed for high density lipoprotein (HDL) cholesterol and triglycerides. Detailed information on the technicalities of the blood analysis is available in the 2004 HSE technical report (Becker et al., 2006). Health conditions. Self-reported doctor’s diagnosis
of health conditions up to and including wave 2 was recorded including cardiovascular disease (angina, myocardial infarction, congestive heart failure, arrhythmia, and stroke), hypertension, diabetes, asthma, and arthritis (osteoarthritis and rheumatoid arthritis). Whether the participant had any respiratory infection in the last three weeks was also collected. Statistical analysis
Variables are presented as means and standard deviations (continuous) or proportions (categorical) for baseline characteristics of study participants stratified by CRP and depressive symptomatology groups. Significance of differences in means was performed with two-sided t-tests, and significance of differences in proportions was conducted with χ 2 tests. We used logistic regression to calculate the odds ratio (OR) and 95% confidence intervals (CI) to examine the direction of the association between CRP and Int J Geriatr Psychiatry 2014
B. Au et al.
depression. First, the relationship between baseline CRP levels and elevated depressive symptoms at follow-up was assessed, adjusting for baseline depression symptoms. Similarly, the relationship between baseline depressive symptoms and high CRP levels at follow-up was assessed, adjusting for baseline CRP concentrations. Because the prevalence of depression across baseline CRP category and the prevalence of high CRP across baseline depression status were above 10%, odds ratio does not approximate risk ratios (Cummings, 2009) and should not be interpreted as such in this study. The contribution of covariates to the CRPdepression directional relations was examined by including each set of covariates as models in the following order: Model 1, baseline levels of the outcome variable; Model 2, socio-demographics; Model 3, health-related behaviors; Model 4, metabolic factors; and Model 5, health conditions. In each subsequent model, all variables from the previous models were retained. Thus, the final model adjusts for all of the covariates. All analyses were performed using STATA/SE version 12 (StataCorp LP, College Station, TX, USA).
Results descriptive statistics
Approximately 32% of the total sample had high CRP concentrations at baseline, 20% had high CRP at both baseline and follow-up, and 18% had newly developed high CRP. Approximately 13% of the total sample had elevated depressive symptoms at baseline, 5% had elevated depressive symptomatology at both baseline and follow-up, and 8% had newly developed elevated depressive symptoms. The baseline sample characteristics according to CRP group are presented in Table 1. The high CRP group differed from the normal CRP in that they were more likely to have elevated depressive symptoms, higher BMI and triglyceride levels, but lower HDL-cholesterol. They were also more likely to be older, female, current smokers, have hypertension, arthritis, asthma, and a respiratory infection in the last three weeks. However, they were less likely to be married, have a university degree or equivalent, employed, and have high physical activity level compared to the normal CRP group. The baseline sample characteristics according to depressive symptomatology group are presented in Table 2. The elevated depressive symptoms group
Table 1 Baseline characteristics of the study sample stratified by CRP group (N = 3397)
Elevated depressive symptoms (%) Age (years) Female (%) Marital status Married (%) Single never married (%) Divorced/separated (%) Widowed (%) Education University degree or equivalent (%) Less than university (%) No qualification (%) Employment status Employed (%) Retired (%) Unemployed (%) Current smoker (%) High physical activity level (%) 2 BMI (kg/m ) Triglycerides (mmol/L) HDL cholesterol (mmol/) Hypertensive (%) Diabetic (%) CVD (%) Arthritic (%) Asthmatic (%) Respiratory infection in last 3 weeks (%)
Normal CRP (≤3.0 mg/L), n = 2319
High CRP (>3.0 mg/L), n = 1078
p-value
10.87 64.10 (8.53) 53.99
15.77 65.58 (9.00) 61.13
The longitudinal associations between C-reactive protein and depressive symptoms: evidence from the English Longitudinal Study of Ageing (ELSA) Bonnie Au1,2, Kimberley J. Smith2,3, Geneviève Gariépy1,2 and Norbert Schmitz1,2,3,4 1
Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada Douglas Mental Health University Institute, Montreal, Quebec, Canada 3 Department of Psychiatry, McGill University, Montreal, Quebec, Canada 4 Montreal Diabetes Research Center, Montreal, Quebec, Canada Correspondence to: B. Au, E-mail: [email protected] 2
Objectives: The inflammatory marker C-reactive protein (CRP) is associated with depression. We exam-
ined the directional relations between CRP and symptoms of depression among older adults. Method: The sample consisted of 3397 participants from the English Longitudinal Study of Ageing, a prospective study of community-dwelling older adults. CRP and depressive symptoms were measured at baseline and follow-up. A high CRP level was dichotomized as >3 mg/L. Elevated depressive symptomatology was defined as ≥4 using the 8-item Center for Epidemiologic Studies Depression Scale. Logistic regressions computed the association between high CRP levels at baseline with elevated depressive symptoms at follow-up, and vice versa. Results: After adjusting for baseline depressive symptoms, baseline high CRP levels were associated with subsequent elevated symptoms of depression (OR = 1.49; 95% CI, 1.19–1.88). This relationship was no longer significant after simultaneous adjustments for metabolic and health variables. In the other direction, after adjusting for baseline CRP levels, baseline elevated depressive symptoms was not associated with subsequent high CRP levels (OR = 1.12; 95% CI, 0.88–1.42). Conclusion: High CRP levels at baseline are related to elevated depressive symptomatology at follow-up due to clinical factors. No association was found in the opposite direction. Copyright # 2014 John Wiley & Sons, Ltd. Key words: depression; inflammation; C-reactive protein; older adults; longitudinal History: Received 20 June 2014; Accepted 18 November 2014; Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/gps.4250
Introduction The older population is the fastest growing age group in the world as a result of longer life expectancy, declining fertility rate, and a shift from infectious to chronic non-communicable diseases as prevailing causes of disability and death (Aging, 2007; Currie, 2013). Depression among older adults is a growing public health concern worldwide (Ustun et al., 2004). Over a third of the population in England is comprised of older adults aged ≥50 years (Statistics, 2013), and the prevalence of depressive symptoms is Copyright # 2014 John Wiley & Sons, Ltd.
estimated at more than 17% among communitydwelling English older adults (Zivin et al., 2010). Depressive symptoms adversely affect the quality of life of older persons in terms of functioning and wellbeing (Penninx et al., 1998), and increase the risks of morbidity and mortality (Lee et al., 2001; Fiske et al., 2009). However, the pathophysiology of depression remains elusive among older adults. Consideration of biological risk factors for depression is important in older age because depression often arises in co-morbidity with chronic medical conditions (Alexopoulos, 2005). These medical
Int J Geriatr Psychiatry 2014
B. Au et al.
conditions are associated with changes in endocrine, cardiovascular, and inflammatory risk factors (Fiske et al., 2009). Given the disease-related processes involved in older ages, it is possible that dysregulation in these biological pathways could be involved in the etiology of depression (Alexopoulos, 2005; Fiske et al., 2009). One biological theory of depression that incorporates disease-relevant pathways is the cytokine hypothesis of depression (Ito and Ikeda, 2003), which posits that increased inflammation is involved in the pathophysiology of depression (Dantzer et al., 2008). Inflammatory markers that are speculated in the biological etiology of depression include interleukin-6 (IL-6) and its ensuing acute phase response C-reactive protein (CRP) (Silić et al., 2012). CRP is a wellestablished marker for inflammation and is gaining increasing attention for its role in the pathophysiology of depression (Howren et al., 2009; Penninx et al., 2013). Prospective data from aging cohorts are needed to ascertain whether inflammation is a cause or consequence of depression. There is a scarcity of studies that have examined the longitudinal relationship between CRP and depressive symptoms among older adults. Results from these studies have been mixed, with some studies finding a prospective association between CRP and incident depression (van den Biggelaar et al., 2007; Luukinen et al., 2010) and others finding no association (Forti et al., 2010; Baune et al., 2012). A recent review using only longitudinal studies found a small association between raised CRP levels with subsequent development of depressive symptoms (Valkanova et al., 2013). However, the meta-analysis consisted of only three studies which assessed the association specifically among older adults, and all three studies analyzed CRP as the baseline exposure and depression as the follow-up outcome which limits inferences on the directionality of the CRP and depression relationship. Only one study has examined the directional relations between CRP and depression among older adults (Stewart et al., 2009), and evidence of weak directional relationships between depressive symptoms and CRP were observed, but neither of the associations was statistically significant. However, the study conducted by Stewart et al. (2009) was limited to a small sample size of 263 healthy volunteers, which may not be representative of a general population of older adults and an underestimation of effects is possible. Furthermore, depressive symptoms and CRP levels were analyzed continuously, which may limit clinical interpretation with regards to defining a caseness for having elevated depressive symptomatology or low-grade inflammation. We aim to add to this area of research by Copyright # 2014 John Wiley & Sons, Ltd.
investigating the associations in a larger representative community-dwelling sample of older adults and analyzing depressive symptoms and CRP levels based on established cut-offs. The main objective of this study is to assess the directional relationship between CRP and depression to determine (a) whether having high CRP level at baseline is associated with occurrence of elevated depressive symptoms at follow-up and (b) whether having elevated depressive symptoms at baseline is associated with high CRP level at follow-up from the English Longitudinal Study of Ageing (ELSA), a prospective study of community-dwelling English older adults. A secondary objective is to evaluate the role of covariates such as socio-demographics, health behaviors, metabolic factors, and heath conditions in the CRP–depression relationship. Methods Design/setting and participants
ELSA is a nationally representative cohort study of older English adults living in households. ELSA consists of men and women born on or before 29 February 1952. The sample was derived from households that had participated in the Health Survey for England (HSE) in 1998, 1999, and 2001. The HSE recruited participants using multistage stratified probability sampling with postcode sectors selected at the first stage and household addresses selected at the second stage. For the present analyses, data from wave 2 (2004–2005) were used as baseline since this was the first occasion when clinical assessments including blood samples were collected by a nurse. Wave 4 (2008–2009) was used as the follow-up since it contains data on both clinical measures (every four years) and depressive symptoms (every two years). Participants provided full informed written consent, and ethical approval was granted by the London Multi-centre Research Ethics Committee. A total of 9432 participants attended the wave 2 core assessment. The present study reports only on participants who consented and were able to give blood (n = 7666) in wave 2 clinical assessment. Missing biological data was mainly because participants did not consent to give blood or were ineligible (people with clotting/bleeding disorders or taking anti-coagulant medication). After excluding participants that did not attend the core and clinical assessments at wave 4 (n = 2506), did not have valid baseline or follow-up CRP measurement (n = 1746), and had missing Int J Geriatr Psychiatry 2014
C-reactive protein and depressive symptoms
baseline or follow-up CES-D score (n = 17), the final analytic sample comprises of 3397 individuals. Compared to the baseline cohort, the analytical sample was slightly younger (64.6 vs. 65.8 years), more likely to be employed (35.8% vs. 24.4%) and involved in high levels of physical activity (23.0% vs. 18.8%). They also had a lower prevalence of diabetes (6.2% vs. 30.2%), cardiovascular conditions (19.5% vs. 43.0%), arthritis (36.4% vs. 52.0%) and asthma (12.8% vs. 33.5%).
Socio-demographic variables. Demographic vari-
ables included age, sex, and marital status (married, single never married, divorced/separated, or widowed). Education was assessed by asking participants to report their highest attained educational qualification (university degree or equivalent, less than university degree, or no qualification). Additional socio-demographic variable included working status (employed, unemployed, or retired). Ethnicity was not included because 99% of the sample was white. Health behaviors. Health-related behaviors included
Measures Depressive symptoms. Symptoms of depression were
assessed using the 8-item Centre of Epidemiological Studies Depression (CES-D) scale (Radloff, 1977; Missinne et al., 2014). Participants responded, yes or no, to items of depressive symptoms including depressed mood, restless sleep, decreased energy, and enjoyment in life, as well as feelings of loneliness and sadness. Symptoms of depression were dichotomized into low (CES-D 3 mg/L) levels. This cut-off value for CRP was based on clinical guidelines from the Centers for Disease Control and Prevention and American Heart Association that concentrations of CRP above 3 mg/L be used to indicate high risk of cardiovascular diseases (Pearson et al., 2003). Furthermore, CRP levels above this concentration have been defined as low-grade inflammation (Das, 2011; Barberato et al., 2013; Sorensen et al., 2014). This classification has also been used in previous studies with depression (Almeida et al., 2007; Almeida et al., 2009). Covariates. We identified potentially relevant socio-
demographic, lifestyle, and clinical contributors in the link between inflammation and depression based on recommendations from a review by O’Connor et al. (2009). Copyright # 2014 John Wiley & Sons, Ltd.
baseline smoking status (smoker or non-smoker) and physical activity. Physical activity was a derived variable based on the combination of occupational and leisure activities that was classified using the Allied Dunbar Survey of Fitness (1992). Level of physical activity was dichotomized into high physical activity versus not high physical activity (i.e. sedentarymoderate). Metabolic measures. Nurses collected anthropometric data (height and weight) and blood samples at both waves. Body mass index (BMI) was derived from weight and height based on the standard formula (kg/m2). Blood samples were also analyzed for high density lipoprotein (HDL) cholesterol and triglycerides. Detailed information on the technicalities of the blood analysis is available in the 2004 HSE technical report (Becker et al., 2006). Health conditions. Self-reported doctor’s diagnosis
of health conditions up to and including wave 2 was recorded including cardiovascular disease (angina, myocardial infarction, congestive heart failure, arrhythmia, and stroke), hypertension, diabetes, asthma, and arthritis (osteoarthritis and rheumatoid arthritis). Whether the participant had any respiratory infection in the last three weeks was also collected. Statistical analysis
Variables are presented as means and standard deviations (continuous) or proportions (categorical) for baseline characteristics of study participants stratified by CRP and depressive symptomatology groups. Significance of differences in means was performed with two-sided t-tests, and significance of differences in proportions was conducted with χ 2 tests. We used logistic regression to calculate the odds ratio (OR) and 95% confidence intervals (CI) to examine the direction of the association between CRP and Int J Geriatr Psychiatry 2014
B. Au et al.
depression. First, the relationship between baseline CRP levels and elevated depressive symptoms at follow-up was assessed, adjusting for baseline depression symptoms. Similarly, the relationship between baseline depressive symptoms and high CRP levels at follow-up was assessed, adjusting for baseline CRP concentrations. Because the prevalence of depression across baseline CRP category and the prevalence of high CRP across baseline depression status were above 10%, odds ratio does not approximate risk ratios (Cummings, 2009) and should not be interpreted as such in this study. The contribution of covariates to the CRPdepression directional relations was examined by including each set of covariates as models in the following order: Model 1, baseline levels of the outcome variable; Model 2, socio-demographics; Model 3, health-related behaviors; Model 4, metabolic factors; and Model 5, health conditions. In each subsequent model, all variables from the previous models were retained. Thus, the final model adjusts for all of the covariates. All analyses were performed using STATA/SE version 12 (StataCorp LP, College Station, TX, USA).
Results descriptive statistics
Approximately 32% of the total sample had high CRP concentrations at baseline, 20% had high CRP at both baseline and follow-up, and 18% had newly developed high CRP. Approximately 13% of the total sample had elevated depressive symptoms at baseline, 5% had elevated depressive symptomatology at both baseline and follow-up, and 8% had newly developed elevated depressive symptoms. The baseline sample characteristics according to CRP group are presented in Table 1. The high CRP group differed from the normal CRP in that they were more likely to have elevated depressive symptoms, higher BMI and triglyceride levels, but lower HDL-cholesterol. They were also more likely to be older, female, current smokers, have hypertension, arthritis, asthma, and a respiratory infection in the last three weeks. However, they were less likely to be married, have a university degree or equivalent, employed, and have high physical activity level compared to the normal CRP group. The baseline sample characteristics according to depressive symptomatology group are presented in Table 2. The elevated depressive symptoms group
Table 1 Baseline characteristics of the study sample stratified by CRP group (N = 3397)
Elevated depressive symptoms (%) Age (years) Female (%) Marital status Married (%) Single never married (%) Divorced/separated (%) Widowed (%) Education University degree or equivalent (%) Less than university (%) No qualification (%) Employment status Employed (%) Retired (%) Unemployed (%) Current smoker (%) High physical activity level (%) 2 BMI (kg/m ) Triglycerides (mmol/L) HDL cholesterol (mmol/) Hypertensive (%) Diabetic (%) CVD (%) Arthritic (%) Asthmatic (%) Respiratory infection in last 3 weeks (%)
Normal CRP (≤3.0 mg/L), n = 2319
High CRP (>3.0 mg/L), n = 1078
p-value
10.87 64.10 (8.53) 53.99
15.77 65.58 (9.00) 61.13
