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NSAIDs may promote a paradoxical pro-inflammatory effect, increasing the risk of blood clots and cardiovascular events.

Non-steroidal anti-inflammatory drugs, or NSAIDs, are among the most widely used drugs worldwide, available in both prescription and over-the-counter forms, such as aspirin, ibuprofen, naproxen, and others. Despite the drugs' anti-inflammatory effects, their chronic use is associated with a higher risk of acute clot-related cardiovascular events, such as heart attack, stroke, or deep-vein thrombosis. Authors of a 2005 article posited that NSAIDs induce a rebound effect that promotes inflammation, driving the formation of blood clots and predisposing a person to acute cardiovascular events.

Inflammation is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes. Inflammation initiates the clotting process and impairs the activity of natural anti-clotting mechanisms.

Most NSAIDs, with the exception of aspirin, dampen inflammation via the inhibition of cyclooxygenases, a family of pro-inflammatory enzymes. However, evidence from animal studies suggests that when these enzymes are inhibited, the body responds by producing more of the enzymes. The authors posited that by turning off the body’s natural inflammatory processes, NSAIDs might drive a compensatory response – ramping up the activity of pro-inflammatory pathways.

Lifestyle behaviors may reduce inflammation and the need for NSAIDs. For example, sauna use reduces levels of pro-inflammatory C-reactive protein and increases levels of anti-inflammatory protein interleukin (IL)-10. Similarly, cold exposure decreased the pro-inflammatory protein IL-2 and the inflammatory E2 series of prostaglandins while increasing the anti-inflammatory protein IL-10. Other lifestyle behaviors that may reduce inflammation include exercise, meditation, and dietary intake of polyphenols.

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