Lee, Jung Hyun
(Graduate School of Public Health, Yonsei University)
,
Yeom, Hyungseon
(Department of Preventive Medicine, Yonsei University College of Medicine)
,
Kim, Hyeon Chang
(Department of Preventive Medicine, Yonsei University College of Medicine)
,
Suh, Il
(Department of Preventive Medicine, Yonsei University College of Medicine)
,
Kim, Mi Kyung
(Department of Preventive Medicine, Hanyang University College of Medicine)
,
Shin, Min-Ho
(Department of Preventive Medicine, Chonnam National University Medical School)
,
Shin, Dong Hoon
(Department of Preventive Medicine, Keimyung University School of Medicine)
,
Koh, Sang-Baek
(Department of Preventive Medicine, Yonsei University Wonju College of Medicine)
,
Ahn, Song Vogue
(Department of Preventive Medicine, Yonsei University Wonju College of Medicine)
,
Lee, Tae-Yong
(Department of Preventive Medicine, Chungnam National University School of Medicine)
,
Ryu, So Yeon
(Department of Preventive Medicine, Chosun University Medical School)
,
Song, Jae-Sok
(Department of Preventive Medicine and Institute of Catholic Kwandong University College of Medicine)
,
Choe, Hong-Soon
(Department of Preventive Medicine and Institute of Catholic Kwandong U)
,
Lee, Young-Hoon
,
Choi, Bo Youl
Objectives: C-reactive protein (CRP), an inflammatory biomarker, has been widely used as a preclinical marker predictive of morbidity and mortality. Although many studies have reported a positive association between CRP and mortality, uncertainty still remains about this association in various popul...
Objectives: C-reactive protein (CRP), an inflammatory biomarker, has been widely used as a preclinical marker predictive of morbidity and mortality. Although many studies have reported a positive association between CRP and mortality, uncertainty still remains about this association in various populations, especially in rural Korea. Methods: A total of 23 233 middle-aged participants (8862 men and 14 371 women) who were free from cardiovascular disease, cancer, and acute inflammation (defined by a CRP level ${\geq}10mg/L$) were drawn from 11 rural communities in Korea between 2005 and 2011. Blood CRP concentration was analyzed as a categorical variable (low: 0.0-0.9 mg/L; intermediate: 1.0-3.0 mg/L; high: 3.1-9.9 mg/L) as well as a continuous variable. Each participant's vital status through December 2013 was confirmed by death statistics from the National Statistical Office. Cox proportional hazard models were used to assess the independent association between CRP and mortality after adjusting for other risk factors. Results: The total quantity of observed person-years was 57 975 for men and 95 146 for women, and the number of deaths was 649 among men and 367 among women. Compared to the low-CRP group, the adjusted hazard ratio for all-cause mortality of the intermediate group was 1.17 (95% confidence interval [CI], 0.98 to 1.40) for men and 1.27 (95% CI, 1.01 to 1.61) for women, and the corresponding values for the high-CRP group were 1.98 (95% CI, 1.61 to 2.42) for men and 1.41 (95% CI, 1.03 to 1.95) for women. Similar trends were found for CRP evaluated as a continuous variable and for cardiovascular mortality. Conclusions: Higher CRP concentrations were associated with higher mortality in a rural Korean population, and this association was more prominent in men than in women.
Objectives: C-reactive protein (CRP), an inflammatory biomarker, has been widely used as a preclinical marker predictive of morbidity and mortality. Although many studies have reported a positive association between CRP and mortality, uncertainty still remains about this association in various populations, especially in rural Korea. Methods: A total of 23 233 middle-aged participants (8862 men and 14 371 women) who were free from cardiovascular disease, cancer, and acute inflammation (defined by a CRP level ${\geq}10mg/L$) were drawn from 11 rural communities in Korea between 2005 and 2011. Blood CRP concentration was analyzed as a categorical variable (low: 0.0-0.9 mg/L; intermediate: 1.0-3.0 mg/L; high: 3.1-9.9 mg/L) as well as a continuous variable. Each participant's vital status through December 2013 was confirmed by death statistics from the National Statistical Office. Cox proportional hazard models were used to assess the independent association between CRP and mortality after adjusting for other risk factors. Results: The total quantity of observed person-years was 57 975 for men and 95 146 for women, and the number of deaths was 649 among men and 367 among women. Compared to the low-CRP group, the adjusted hazard ratio for all-cause mortality of the intermediate group was 1.17 (95% confidence interval [CI], 0.98 to 1.40) for men and 1.27 (95% CI, 1.01 to 1.61) for women, and the corresponding values for the high-CRP group were 1.98 (95% CI, 1.61 to 2.42) for men and 1.41 (95% CI, 1.03 to 1.95) for women. Similar trends were found for CRP evaluated as a continuous variable and for cardiovascular mortality. Conclusions: Higher CRP concentrations were associated with higher mortality in a rural Korean population, and this association was more prominent in men than in women.
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제안 방법
Another aim of our study was to evaluate the effect of hypertension in modifying the association between blood CRP concentrations and mortality. However, our analysis that was stratified according to the presence of hypertension did not show a significant interaction (p for interaction>0.
05). As adjustment variables, we selected age, rural region, BMI, educational status, alcohol use, smoking status, regular exercise, the presence of disease (hypertension, diabetes, and dyslipidemia), SBP, DBP, and fasting concentrations of blood glucose, total cholesterol, triglycerides, and HDL cholesterol. Adjustment variables were selected based on previous studies [11,13,17].
, non-linear) hazard functions [25]. In this method, we selected five CRP concentration values as knots based on CRP concentration percentiles, tested the linear and non-linear associations between knots using a cubic function, and presented the integrated graph smoothly. Since the RCS could be affected by outliers, we excluded values lower than the 1st percentile and greater than the 99th percentile.
Information about demographic factors, socioeconomic status, health behaviors, and disease history were collected using a standardized questionnaire. Educational status was used to represent socioeconomic status, and was defined as elementary school or below, middle school, high school, and university or above.
An interaction term was created between hypertension status and CRP and was added into the Cox proportional hazard model. Sensitivity analysis was performed by excluding deaths that occurred within two years from the month that each participant first participated in the study in order to rule out deaths caused by unknown underlying diseases. Since blood CRP concentrations were right-skewed, another sensitivity analysis was performed using log-transformed blood CRP concentrations.
To verify participants’ vital status, their records in our study were crosschecked with death statistics from the National Statistical Office via the Korea Centers for Disease Control and Prevention using an anonymized form through December 2013.
대상 데이터
Next, we excluded 227 participants whose vital status could not be confirmed, as well as 1604 participants whose CRP concentrations were not measured. Finally, we excluded 442 participants due to missing data in some independent variables, as well as two participants who died in the same month that they were enrolled in the study. Thus, a total of 23 233 people (8862 men and 14 371 women) were included in the final analysis.
In brief, a total of 28 338 community dwellers (age ≥40 years) were recruited from 11 rural communities in Korea from 2005 to 2011. In eight communities, the study participants were recruited beginning in 2005, and those in the other three communities were recruited beginning in 2006. The follow-up is ongoing, and in this study, we assessed mortality cases based on data from the National Statistical Office.
Finally, we excluded 442 participants due to missing data in some independent variables, as well as two participants who died in the same month that they were enrolled in the study. Thus, a total of 23 233 people (8862 men and 14 371 women) were included in the final analysis. All participants provided written informed consent, and the study protocol was approved by the institutional review board of each institution that participated in KoGES_CAVAS.
데이터처리
Since blood CRP concentrations were right-skewed, another sensitivity analysis was performed using log-transformed blood CRP concentrations. All statistical analyses were performed using SAS version 9.3 (SAS Institute Inc., Cary, NC, USA), and RCS analysis was carried out using the SAS LGTPHCURV9 macro [26]. The p-values <0.
이론/모형
Since the RCS could be affected by outliers, we excluded values lower than the 1st percentile and greater than the 99th percentile. An interaction term was created between hypertension status and CRP and was added into the Cox proportional hazard model. Sensitivity analysis was performed by excluding deaths that occurred within two years from the month that each participant first participated in the study in order to rule out deaths caused by unknown underlying diseases.
Laboratory evaluations were performed using blood samples obtained after participants had fasted overnight. Blood concentrations of glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides were measured using the enzyme method (ADVIA 1650 and ADVIA 1800; Siemens Healthineers, Deerfield, IL, USA). Low-density lipoprotein (LDL) cholesterol levels were calculated using the Friedewald formula [24] in individuals with blood triglyceride levels <4.
We used the t-test, analysis of variance, the Mann-Whitney test, the Kruskal-Wallis test, and the chi-square test for comparisons. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) between CRP and mortality using the Cox proportional hazard model. The proportional hazard assumption was assessed by including interactions with time as time-dependent covariates in our model, and no obvious violations were found (p for proportional test >0.
성능/효과
Fourth, the participants’ history of taking medications with direct effects on CRP concentrations was not available in our data.
In conclusion, blood CRP concentration showed a positive association with all-cause mortality and cardiovascular mortality in a rural Korean population. The strength of the association among men was greater than among women.
The proportional hazard assumption was assessed by including interactions with time as time-dependent covariates in our model, and no obvious violations were found (p for proportional test >0.05).
61) for women. The results of the Cox regression analysis of CRP levels on cardiovascular mortality were similar to those between CRP levels and all-cause mortality, although the relationship was only significant for continuous CRP concentrations in men. In the sensitivity analysis, in which deaths occurring within two years from the beginning of study participation were excluded, the HR was attenuated, but the tendency was consistent.
후속연구
In other studies that showed significant associations between CRP and mortality for men, significant associations were rarely found in women [11,27]. Due to this gender-based discrepancy, further evaluation will be needed regarding the different association patterns observed between CRP and mortality according to gender. Meanwhile, associations between CRP and cardiovascular mortality were not found to be significant (Figure 1).
This association was not found to be modified by the presence of hypertension. Further evaluation of the associations between CRP and other outcomes, such as hypertension or CVD incidence, is needed.
Not only disease presence, but disease incidence may affect the association between CRP and mortality. Further research with respect to disease incidence therefore needs to be carried out. Third, a limited approach to disease history was another limitation of our study.
참고문헌 (37)
1 Libby P Inflammatory mechanisms: the molecular basis of inflammation and disease Nutr Rev 2007 65 12 Pt 2 S140 S146 18240538
2 Shacter E Weitzman SA Chronic inflammation and cancer Oncology (Williston Park) 2002 16 2 217 226 11866137
3 Willerson JT Ridker PM Inflammation as a cardiovascular risk factor Circulation 2004 109 21 Suppl 1 II2 II10 15173056
4 Windgassen EB Funtowicz L Lunsford TN Harris LA Mulvagh SL C-reactive protein and high-sensitivity C-reactive protein: an update for clinicians Postgrad Med 2011 123 1 114 119
5 NACB LMPG Committee Members Myers GL Christenson RH Cushman M Ballantyne CM Cooper GR National Academy of Clinical Biochemistry Laboratory Medicine Practice guidelines: emerging biomarkers for primary prevention of cardiovascular disease Clin Chem 2009 55 2 378 384 19106185
6 Makita S Nakamura M Satoh K Tanaka F Onoda T Kawamura K Serum C-reactive protein levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population Atherosclerosis 2009 204 1 234 238 18790479
7 Emerging Risk Factors Collaboration Kaptoge S Di Angelantonio E Lowe G Pepys MB Thompson SG C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis Lancet 2010 375 9709 132 140 20031199
8 Ridker PM High-sensitivity C-reactive protein as a predictor of all-cause mortality: implications for research and patient care Clin Chem 2008 54 2 234 237 18223130
9 Ahmadi-Abhari S Luben RN Wareham NJ Khaw KT Seventeen year risk of all-cause and cause-specific mortality associated with C-reactive protein, fibrinogen and leukocyte count in men and women: the EPIC-Norfolk study Eur J Epidemiol 2013 28 7 541 550 23821244
10 Goyal A Terry MB Jin Z Siegel AB C-reactive protein and colorectal cancer mortality in U.S. adults Cancer Epidemiol Biomarkers Prev 2014 23 8 1609 1618 24867266
11 Sung KC Ryu S Chang Y Byrne CD Kim SH C-reactive protein and risk of cardiovascular and all-cause mortality in 268 803 East Asians Eur Heart J 2014 35 27 1809 1816 24569028
12 Doran B Zhu W Muennig P Gender differences in cardiovascular mortality by C-reactive protein level in the United States: evidence from the National Health and Nutrition Examination Survey III Am Heart J 2013 166 1 45 51 23816020
13 Kim KI Oh SW Ahn S Heo NJ Kim S Chin HJ CRP level and HDL cholesterol concentration jointly predict mortality in a Korean population Am J Med 2012 125 8 787 795 e4 22840665
14 Ding D Wang M Su D Hong C Li X Yang Y Body mass index, high-sensitivity C-reactive protein and mortality in Chinese with coronary artery disease PLoS One 2015 10 8
15 Sung JW Lee SH Byrne CD Chung PW Won YS Sung KC High-sensitivity C-reactive protein is associated with the presence of coronary artery calcium in subjects with normal blood pressure but not in subjects with hypertension Arch Med Res 2014 45 2 170 176 24508289
16 Kengne AP Batty GD Hamer M Stamatakis E Czernichow S Association of C-reactive protein with cardiovascular disease mortality according to diabetes status: pooled analyses of 25,979 participants from four U.K. prospective cohort studies Diabetes Care 2012 35 2 396 403 22210562
17 Koenig W Khuseyinova N Baumert J Meisinger C Prospective study of high-sensitivity C-reactive protein as a determinant of mortality: results from the MONICA/KORA Augsburg Cohort Study, 1984-1998 Clin Chem 2008 54 2 335 342 18156284
18 Yusuf S Reddy S Ounpuu S Anand S Global burden of cardiovascular diseases. Part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies Circulation 2001 104 23 2855 2864 11733407
19 Miranda JJ Gilman RH Smeeth L Differences in cardiovascular risk factors in rural, urban and rural-to-urban migrants in Peru Heart 2011 97 10 787 796 21478383
21 Kim Y Han BG KoGES group Cohort profile: the Korean genome and epidemiology study (KoGES) Consortium Int J Epidemiol 2016 http://dx.doi.org/10.1093/ije/dyv316
22 Lee EH Park SK Ko KP Cho IS Chang SH Shin HR Cigarette smoking and mortality in the Korean Multi-center Cancer Cohort (KMCC) study J Prev Med Public Health 2010 43 2 151 158 (Korean) 20383048
23 World Health Organization The Asia-Pacific perspective: redefining obesity and its treatment [cited 2016 Sep 4] Available from: http://www.wpro.who.int/nutrition/documents/docs/Redefiningobesity.pdf
24 Friedewald WT Levy RI Fredrickson DS Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge Clin Chem 1972 18 6 499 502 4337382
26 Li R Hertzmark E Louie M Chen L Spiegelman D The SAS LGTPHCURV9 macro 2011 [cited 2016 Sep 4]. Available from: https://cdn1.sph.harvard.edu/wp-content/uploads/sites/271/2012/09/lgtphcurv9_7-3-2011.pdf
27 Iso H Cui R Date C Kikuchi S Tamakoshi A JACC Study Group C-reactive protein levels and risk of mortality from cardiovascular disease in Japanese: the JACC Study Atherosclerosis 2009 207 1 291 297 19482283
28 Currie CJ Poole CD Conway P Evaluation of the association between the first observation and the longitudinal change in C-reactive protein, and all-cause mortality Heart 2008 94 4 457 462 17761503
29 Pearson TA Mensah GA Alexander RW Anderson JL Cannon RO 3rd Criqui M Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association Circulation 2003 107 3 499 511 12551878
30 Woloshin S Schwartz LM Distribution of C-reactive protein values in the United States N Engl J Med 2005 352 15 1611 1613
31 Saito I Sato S Nakamura M Kokubo Y Mannami T Adachi H A low level of C-reactive protein in Japanese adults and its association with cardiovascular risk factors: the Japan NCVC-Collaborative Inflammation Cohort (JNIC) study Atherosclerosis 2007 194 1 238 244 16963054
32 Zhao Y Wang R Ma X Yan X Zhang Z He X Distribution of C-reactive protein and its association with cardiovascular risk factors in a population-based sample of Chinese Dis Markers 2010 28 6 333 342 20683147
33 Organization for Economic Cooperation and Development Health status [cited 2015 Nov 29]. Available from: http://stats.oecd.org/index.aspx?DataSetCode=HEALTH_STAT
34 Kuoppamäki M Salminen M Vahlberg T Irjala K Kivelä SL Räihä I High sensitive C-reactive protein (hsCRP), cardiovascular events and mortality in the aged: a prospective 9-year follow-up study Arch Gerontol Geriatr 2015 60 1 112 117 25456891
35 Smith KB Humphreys JS Wilson MG Addressing the health disadvantage of rural populations: how does epidemiological evidence inform rural health policies and research? Aust J Rural Health 2008 16 2 56 66 18318846
36 Hage FG C-reactive protein and hypertension J Hum Hypertens 2014 28 7 410 415 24226100
37 Ridker PM Danielson E Fonseca FA Genest J Gotto AM Jr Kastelein JJ Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial Lancet 2009 373 9670 1175 1182 19329177
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