Lower Blood Pressure Extremes Precede the Recorded Diagnosis of Fibromyalgia by up to Two Decades: A Population-Based...

Fibromyalgia (FM) has been linked to autonomic dysregulation, but population-level evidence on blood pressure (BP) in FM is sparse, and whether BP differences are present before diagnosis is unknown. We conducted a population-based case-control study within Leumit Health Services, Israel, comparing 15,869 adults with FM with 79,345 controls matched 5:1 on sex, birth year, and membership start. BP, heart rate (HR), and body temperature were summarized as each individual's minimum, mean, and maximum values over the full observation period and within a pre-diagnosis window extending up to 20 years before the index date with a 30-day blackout. Over the full period, FM patients had lower minimum systolic BP (99.1 ± 11.1 vs. 102.6 ± 12.3 mmHg; standardized mean difference [SMD] -0.29, 95% CI -0.31 to -0.27), lower minimum diastolic BP and pulse pressure, and higher maximum HR (SMD +0.22), whereas mean systolic BP differed little (SMD -0.08). The lower-tail BP difference was already present before diagnosis (minimum systolic BP -3.27 mmHg, 95% CI -3.51 to -3.04; SMD -0.24), in every interval from 20 years before the index date, and with 90-, 180-, and 365-day blackouts and across diagnostic-criteria eras. FM patients had more BP readings (22.1 vs. 15.3 per patient), and greater measurement intensity amplified the observed difference; nevertheless, the association persisted, attenuated, when measurement opportunity was standardized (first 3, 5, or 10 readings; measurement count strata; patient-level 10th percentile) and after multivariable adjustment for measurement intensity and cardiometabolic and cardiovascular covariates (-1.18 mmHg, 95% CI -1.37 to -0.99). The HR difference was small after adjustment (+0.25 bpm, 95% CI 0.03 to 0.48). Coded hypotensive, orthostatic, and autonomic diagnoses and dispensing of midodrine and fludrocortisone were more frequent in FM before diagnosis. A modest but reproducible lower-tail BP difference therefore precedes the recorded diagnosis of FM by many years. Because symptoms also antedate diagnosis, these data establish precedence over diagnosis rather than over disease onset, and they are compatible with, but do not prove, altered cardiovascular-autonomic regulation.