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Link to original content: http://pubmed.ncbi.nlm.nih.gov/32221345/
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. 2020 Mar 27;10(1):5605.
doi: 10.1038/s41598-020-62391-3.

Systemic inflammation is associated with incident stroke and heart disease in East Asians

Mohd A Karim  1 , Christiana Kartsonaki  1   2 , Derrick A Bennett  1 , Iona Y Millwood  1   2 , Michael R Hill  1   2 , Daniel Avery  1 , Zheng Bian  3 , Huaidong Du  1   2 , Yu Guo  3 , Yijian Qian  4 , Chan Qu  5 , Iain Turnbull  1 , Dan Schmidt-Valle  1 , Chunmei Wang  4 , Canqing Yu  3 , Jun Lv  6 , Junshi Chen  7 , Robert Clarke  1 , Liming Li  6 , Zhengming Chen  1 , Michael V Holmes  8   9   10 , Robin G Walters  11   12 ; China Kadoorie Biobank Collaborative Group
Collaborators, Affiliations

Systemic inflammation is associated with incident stroke and heart disease in East Asians

Mohd A Karim et al. Sci Rep. .

Erratum in

Abstract

Systemic inflammation, reflected by increased plasma concentrations of C-reactive protein (CRP) and fibrinogen, is associated with increased risk of coronary heart disease, but its relevance for stroke types remains unclear. Moreover, evidence is limited in non-European populations. We investigated associations of CRP and fibrinogen with risks of incident major coronary events (MCE), ischemic stroke (IS) and intracerebral hemorrhage (ICH) in a cohort of Chinese adults. A nested case-control study within the prospective China Kadoorie Biobank included 1,508 incident MCE cases, 5,418 IS cases, 4,476 ICH cases, and 5,285 common controls, aged 30-79 years. High-sensitivity CRP and low-density lipoprotein cholesterol (LDL-C) were measured in baseline plasma samples from all participants, and fibrinogen in a subset (n = 9,380). Logistic regression yielded adjusted odds ratios (ORs) per SD higher usual levels of log-transformed CRP and fibrinogen. The overall mean (SD) baseline LDL-C was 91.6 mg/dL (24.0) and geometric mean (95% CI) CRP and fibrinogen were 0.90 mg/L (0.87-0.93) and 3.01 g/L (2.98-3.03), respectively. There were approximately log-linear positive associations of CRP with each outcome, which persisted after adjustment for LDL-C and other risk factors, with adjusted ORs (95% CI) per SD higher CRP of 1.67 (1.44-1.94) for MCE and 1.22 (1.10-1.36) for both IS and ICH. No associations of fibrinogen with MCE, IS, or ICH were identified. Adding CRP to prediction models based on established risk factors improved model fit for each of MCE, IS, and ICH, with small improvements in C-statistic and correct reclassification of controls to lower risk groups. Among Chinese adults, who have low mean LDL-C, CRP, but not fibrinogen, was independently associated with increased risks of MCE and stroke.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Cross-sectional associations of high-sensitivity C-reactive protein (CRP) with selected cardiovascular disease (CVD) risk factors. Analyses were carried out only in controls (n = 5,285). Cut-offs for biomarker quintiles were based on their distribution in controls only. Geometric mean of CRP was adjusted for age, age2, sex and region. P-trend was calculated using chi-square test statistic with 1 degree of freedom. Error bars represent 95% CI for each quintile.
Figure 2
Figure 2
Risk of Major Coronary Events, Ischemic Stroke, and Intracerebral hemorrhage by quintiles of C-reactive protein (CRP) and fibrinogen. Models were adjusted for age, age2 and sex (Base model) and additionally for income, occupation, education, SBP, BMI, diabetes, physical activity, standing height, smoking, alcohol, LDL-C and TG (Full model). These models were fitted separately for each of the 10 study areas for each quintile and estimates were meta-analyzed; in each quintile, study areas were excluded when models failed to converge (9 models out of 600 models). Cut-offs for CRP and Fibrinogen quintiles were based on their distribution in the combined case-control cohort (CRP: 0.37 mg/l, 0.70 mg/l, 1.28 mg/l, and 2.59 mg/l; Fibrinogen: 2.47 g/l, 2.81 g/l, 3.14 g/l, and 3.60 g/l). Error bars represent 95% floated confidence intervals (CI). The areas of the boxes are proportional to the inverse of the variance of the log ORs. OR, CRP, and fibrinogen are plotted on log scales.
Figure 3
Figure 3
Risk of (A) Major Coronary Events, (B) Ischemic Stroke, and (C) Intracerebral hemorrhage per standard deviation (SD) of usual log-transformed high-sensitivity C-reactive protein (CRP). Models were adjusted for age, age2 and sex (base model) and additionally for income, occupation, education, SBP, BMI, diabetes, physical activity, standing height, smoking, alcohol, LDL-C and TG (Full model). The models were fitted separately for each of the 10 study areas and estimates were meta-analyzed. Error bars represent 95% confidence intervals (CI). The areas of the boxes are proportional to the inverse of the variance of the log ORs.
Figure 4
Figure 4
Risk of Major Coronary Events, Ischemic Stroke, and Intracerebral hemorrhage per standard deviation (SD) of usual log-transformed high-sensitivity C-reactive protein (CRP) by pre-specified subgroups. Models were adjusted (where appropriate) for age, age2 and sex (base model) and additionally for income, occupation, education, SBP, BMI, diabetes, physical activity, standing height, smoking, alcohol, LDL-C and TG. The models were fitted separately for each of the 10 study areas in each subgroup strata and estimates were meta-analyzed; in each subgroup strata, study areas were excluded when models failed to converge (62 models out of 750 models). Error bars represent 95% confidence intervals (CI). The sizes of the boxes are proportional to the inverse of the variance of the log ORs. The dotted line represents the overall adjusted OR. The open diamond represents the overall adjusted OR and its 95% CI. MET: metabolic equivalent of task; p-het: p-value for heterogeneity; p-trend: p-value for trend.
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