Modifiable lifestyle risk factors and C-reactive protein in patients with coronary artery disease: Implications for an anti-inflammatory treatment target population
Authors: Blaum Christopher , Brunner Fabian J , Kröger Friederike , Braetz Julian , Lorenz Thiess , Goßling Alina , Ojeda Francisco , Koester Lukas , Karakas Mahir , Zeller Tanja , Westermann Dirk , Schnabel Renate , Blankenberg Stefan , Seiffert Moritz , Waldeyer Christoph 
Published: November 2019

Abstract

Background
Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) are associated with increased inflammation represented by elevated C-reactive protein (CRP) levels. Lifestyle changes may influence the inflammatory burden in patients with CAD, relevantly modifying the target population for emerging anti-inflammatory compounds.

Aims
The aims of this study were to analyse the association of modRF and CRP levels in CAD patients, and to define a potential target population for anti-inflammatory treatment with and without the optimisation of modRF.

Methods
We included all patients with angiographically documented CAD from the observational cohort study INTERCATH. Patients with recent myocardial infarction, malignancy, infectious disease, and pre-existing immunosuppressive medication including a history of solid organ transplantation were excluded. Overweight (body mass index (BMI) ≥ 25 kg/m2), smoking, lack of physical activity (PA; &lt;1.5 h/week), and poor diet (≤12 points of an established Mediterranean diet score (MDS), range 0–28 points) were considered as modRF. CRP was measured by a high-sensitivity assay (hsCRP) at baseline. We performed multivariable linear regressions with log-transformed hsCRP as the dependent variable. Based on these associations, we calculated potential hsCRP levels for each patient, assuming optimisation of the individual modRF.

Results
Of 1014 patients, 737 (73%) were male, the mean age was 69 years, and 483 (48%) had an hsCRP ≥ 2 mg/l. ModRF were significantly overrepresented in patients with hsCRP ≥ 2 mg/l compared to patients with an hsCRP &lt; 2 mg/l (BMI ≥ 25 kg/m2: 76% vs 61%; PA &lt; 1.5 h/week: 69% vs 57%; MDS ≤ 12: 46% vs 37%; smoking: 61% vs 54%; p &lt; 0.05 for all). hsCRP increased with the incremental number of modRF present (median hsCRP values for N = 0, 1, 2, 3, and 4 modRF: 1.1, 1.0, 1.6, 2.4, 2.8 mg/l, p &lt; 0.001). Multivariable linear regression adjusting for age, sex, intake of lipid-lowering medication, and diabetes mellitus revealed independent associations between log-transformed hsCRP and all modRF (BMI ≥ 25 kg/m2: exp(ß) = 1.55, p &lt; 0.001; PA &lt; 1.5 h/week: exp(ß) = 1.33, p &lt; 0.001; MDS ≤ 12: exp(ß) = 1.18, p = 0.018; smoking: exp(ß) = 1.18, p = 0.019). Individual recalculation of hsCRP levels assuming optimisation of modRF identified 183 out of 483 (38%) patients with hsCRP ≥ 2 mg/l who could achieve an hsCRP &lt; 2 mg/l via lifestyle changes.

Conclusion
modRF are strongly and independently associated with CRP levels in patients with CAD. A relevant portion of CAD patients with high inflammatory burden could achieve an hsCRP &lt; 2 mg/l by lifestyle changes alone. This should be considered both in view of the cost and side-effects of pharmacological anti-inflammatory treatment and for the design of future clinical trials in this field.