Modifiable risk factors and inflammatory burden stratified by the presence and extent of atherosclerotic cardiovascular disease: insights from a population based cohort study
Authors: Bay B , Blaum C , Kellner C , Bei Der Kellen R , Ojeda F , Waibel J , Arnold N , Behrendt C A , Zyriax B , Rimmele D L , Twerenbold R , Blankenberg S , Brunner F J , Waldeyer C 
Published: November 2023

Abstract

Background/Introduction
Inflammation is recognized as a residual risk factor and mediator in patients with Atherosclerotic Cardiovascular Disease (ASCVD). High-sensitivity C-Reactive Protein (hsCRP), a marker of systemic inflammation, can be affected by modifiable risk factors (modRF). On the other hand, ASCVD and its extent might modify hsCRP levels. Data regarding the relationship between hsCRP, modRF and the extent of ASCVD remain scarce.

Purpose
We aimed to analyse the inflammatory burden in relation to the number of vascular beds affected by atherosclerosis and modRF in a contemporary large-scale population cohort.

Methods
After exclusion of individuals with inflammatory disorders, cancer, hsCRP concentrations &gt;10 mg/L, missing hsCRP values and/or missing covariates 3,348 cases were left for analysis. Vascular beds affected were defined as coronary, peripheral and cerebrovascular atherosclerotic disease. ModRF were classified as follows: Lack of physical activity (PA) as &lt;1.5 hours/week of exercise, a BMI ≥25 kg/m2 was considered as overweight, active smoking was defined as either current or quitted smoking within the last 6 months, and lastly poor adherence to a Mediterranean diet as a simple Mediterranean diet score (sMDS) of ≤2 points. Multivariable analyses were computed with hsCRP as dependent variable and modRF as covariates according to the number of vascular beds affected adjusting for age, sex, diabetes and intake of cholesterol-lowering drugs.

Results
Of the 3,348 participants at baseline 1,622 (48.1%) were female and mean age was 62 (1st, 3rd quartile: 54, 69) years. Concerning modRF 1,199 (39.5%) individuals showed low levels of PA, 1,877 (58.7%) were defined as overweight, poor adherence to MDS was determined in 1,421 (51.9%) participants and 694 (20.8%) were active smokers. Whilst no ASCVD was present in 1,612 (48.1%) participants, 1,134 (33.9%) and 602 (18.0%) individuals displayed atherosclerosis in 1 or ≥2 vascular beds, respectively. We found a stepwise increase of hsCRP levels with each incremental increase of modRF (median hsCRP for 0–4 modRF: 0.7, 0.9, 1.2, 1.5, 2.5 mg/L, respectively; p &lt;0.05) and according to the number of vascular beds (median hsCRP for 0-≥2 vascular beds affected: 1.0, 1.1, 1.3 mg/L, respectively; p &lt;0.05). The highest hsCRP concentration was found in individuals with atherosclerosis ≥2 beds and 4 modRF (Figure 1). In multivariable regression analyses, an independent association for increasing numbers of modRF with hsCRP levels across the extent of ASCVD was demonstrated (Table 1).

Conclusion
We demonstrate an increasing inflammatory burden according to the number of modRF and also with the presence and extent of ASCVD in a contemporary population-based cohort. These findings emphasize the important role of subclinical inflammation in the pathogenesis of ASCVD, and might be helpful for the definition of target populations for anti-inflammatory compounds across the extent of atherosclerotic disease.Figure 1Table 1