Elevated Neutrophil to Lymphocyte Ratio in Older Adults with Cocaine Use Disorder as a Marker of Chronic Inflammation

Abstract

Objective: The neutrophil to lymphocyte ratio (NLR) is a non-specific, easy-to-obtain marker of inflammation associated with morbidity and mortality in systemic, psychiatric, and age-related inflammatory conditions. Given the growing trend of substance use disorder (SUD) in older adults, and the relationship between inflammation and SUD elevated NLR may serve as a useful inflammatory biomarker of the combined burden of aging and SUD. The present study focused on cocaine use disorder (CUD) to examine if cocaine adds further inflammatory burden among older adults, by comparing NLR values between older adults with CUD and a non-cocaine using, aged-matched, nationally representative sample.

Methods: The dataset included 107 (86% male) participants (aged 50-65 years) with cocaine use disorder. NLR was derived from complete blood count tests by dividing the absolute value of peripheral neutrophil concentration by lymphocyte concentration. For comparison, we extracted data from age-matched adults without CUD using the National Health and Nutrition Examination Survey. Individuals with immunocompromising conditions were excluded (e.g., rheumatoid arthritis and sexually transmitted infections such as HIV). A doubly-robust inverse probability-weighted regression adjustment (IPWRA) propensity score method was used to estimate group differences on NLR while controlling for potential confounding variables (age, gender, race, income, nicotine, marijuana and alcohol use).

Results: The IPWRA model revealed that the CUD sample had significantly elevated NLR in comparison to non-cocaine users, with a moderate effect size (β weight = 0.67).

Conclusion: Although non-specific, NLR represents a readily obtainable inflammatory marker for SUD research. CUD may add further inflammatory burden to aging cocaine users.

Keywords: Aging; Cocaine; Inflammation; Lymphocytes; Neutrophils..

Fig. 1

Cocaine use disorder (CUD) sample consort. ^aParticipants with the following existing pro-inflammatory conditions associated with normal aging were included in the sample: hypertension, elevated serum glucose, diabetes, and hyperlipidemia. ^bParticipants were excluded if they reported any illicit drug use other than cocaine and marijuana. Participants were excluded if they had irretrievable files or missing LabCorp data (n = 56). Participants were also excluded if they were on anti-inflammatory medications or had inflammatory medical conditions (n = 28) including hepatitis C, HIV, rheumatoid arthritis, syphilis, and trichomoniasis.

Fig. 2

National Health and Nutrition Examination Survey (NHANES) sample consort. ^aExclusionary criteria (other than age) were as follows. Participants were excluded if they reported using the following illicit drugs: cocaine, heroin, methamphetamine, or anabolic steroids. Participants were also excluded if they reported any of the following inflammatory diseases or conditions: rheumatoid arthritis/psoriatic arthritis, gout, liver disease, cancer, preventative aspirin use, or asthma attack within the past year. The following sexually transmitted infections were also exclusionary: hepatitis B, hepatitis C, HIV or chlamydia. Participants were excluded if they had any of the following conditions that may affect inflammation within the past 30 days: flu, pneumonia, ear infection, common cold, or stomach/intestinal illness. Participants reporting medications potentially influencing the central nervous system or inflammatory processes were excluded. For example: anti-fungals, anti-infectives, penicillin, analgesics, hormone modifiers, steroids, immunosuppressive agents, and antipsychotics.

Fig. 3

Neutrophil to lymphocyte ratio values from the propensity score matching model. Error bars represent standard deviations. CUD, cocaine use disorder; NLR, neutrophil to lymphocyte ratio.