Our pilot studies (PSs) show that chronic low blood flow in fibromyalgia is associated with muscle pain, headaches, increased left ventricular muscle collagen (LVMC), and coronary artery stenosis (CAS), suggesting hypoxic injury. A predictive relationship was found by blind correlation between high adrenergic neurovascular tone (ANVT)/duration of illness (years) and the increase in LVMC and CAS in pilot studies, both at r = .97, p < .001. ANVT is measured by systolic time intervals (STI = PEP/LVET × 100%). Therapy resulting in reduction of ANVT with increased systemic flow (cardiac output [CO]) resulted in significantly reduced symptom levels (SL) in PSs. Prospective patients were selected by criteria of the America College of Rheumatology with normal C-reactive protein, systolic blood pressure (SBP) < 121, LDL < 103, HbA1c < 6.0, Hgb > 12, and nonsmokers. These were age 16 to 65 years, 7/1 female/male, with the mean duration of disease at 6 years for group (G)1 (32 patients) and 12 years for G2 (31 patients). G1 and G2 were compared with age-/sex-/race-matched normal controls (C = 40 patients). Serial measurements were made of SBP, STI, CO, systemic vascular resistance (SVR), LV end diastolic volume (EDV = cc/m2), LVMC, right (R) CAS, and left anterior descending (LAD) CAS by our previously reported ultrasonic methods. Patients' SLs were recorded at 0 to 100 (fatigue + pain). Data were placed into a blind matrix for analysis later. Treatment (Rx) (as in PS) with diltiazem CD 240 to 360 mg q/d and amitriptyline 10 to 125 mg q/d resulted in significant improvement in SL (p < .01 by t-test [TT]) as shown below from time (T)1 (start) to T2 (duration of Rx) (1/2). G1 was treated for 6 years and G2 for 12 years.
Prospective Results Group means shown. See Table. Where: * = Significantly different from C at p < .01 by TT. G1 and G2 were found to be significantly different from C by high ANVT (low STIs), high SVR, low CO, and higher LVMC at T1. G2 was shown to be significantly different than G1 at T1 by the following: EDV, LVMC, RCAS, and LADCAS, revealing the significance of the duration of illness (p < .01 by TT). Regression analysis of G1 + G2 demonstrated the percentage of CAS and the percentage of LVMC were predicted by ANVT (STI)/duration of illness at T1 (both at r = .97, p < .001), using PS equations. This multivariant analysis reveals that STI and duration of illness were the only significant parameters explaining 94% (R2 = .94) of the variability of the relationships at T1. Rx significantly reduced ANVT and significantly increased CO. This resulted in significantly regressed LVMC and %CAS. Reduction in LVMC resulted in significantly increased LVED volume/M2 at T2, reversing the restrictive cardiomyopathy, which was present at T1. The CAS at T1 was significantly greater in the larger RCA (> LAD) (p < .01 by TT) in all cases, as in PS, suggesting a chronic wall tension-hypoxic injury. The changes in CAS and LVMC paralleled each other, as shown by the regression analyses supporting systemic hypoxia as the injury at T1 since critical %CAS (> 70%) was not present. Thus, reduction in ANVT and increase in CO resulted in reversal of this ischemic systemic ANVT disorder.