Cardioprotective potential of lithium and role of fractalkine in euthymic patients with bipolar disorder

Abstract

Objective: Over a half century, lithium has been used as the first-line medication to treat bipolar disorder. Emerging clinical and laboratory studies suggest that lithium may exhibit cardioprotective effects in addition to neuroprotective actions. Fractalkine (CX3CL1) is a unique chemokine associated with the pathogenesis of mood disorders and cardiovascular diseases. Herein we aimed to ascertain whether lithium treatment is associated with favorable cardiac structure and function in relation to the reduced CX3CL1 among patients with bipolar disorder. Methods: We recruited 100 euthymic patients with bipolar I disorder aged over 20 years to undergo echocardiographic study and measurement of plasma CX3CL1. Associations between lithium treatment, cardiac structure and function and peripheral CX3CL1 were analyzed according to the cardiovascular risk. The high cardiovascular risk was defined as (1) age ⩾ 45 years in men or ⩾ 55 years in women or (2) presence of concurrent cardiometabolic diseases. Results: In the high cardiovascular risk group ( n = 61), patients who received lithium as the maintenance treatment had significantly lower mean values of left ventricular internal diameters at end-diastole (Cohen’s d = 0.65, p = 0.001) and end-systole (Cohen’s d = 0.60, p = 0.004), higher mean values of mitral valve E/A ratio (Cohen’s d = 0.51, p = 0.019) and superior performance of global longitudinal strain (Cohen’s d = 0.51, p = 0.037) than those without lithium treatment. In addition, mean plasma levels of CX3CL1 in the high cardiovascular risk group were significantly lower among patients with lithium therapy compared with those without lithium treatment ( p = 0.029). Multiple regression models showed that the association between lithium treatment and mitral value E/A ratio was contributed by CX3CL1. Conclusion: Data from this largest sample size study of the association between lithium treatment and echocardiographic measures suggest that lithium may protect cardiac structure and function in patients with bipolar disorder. Reduction of CX3CL1 may mediate the cardioprotective effects of lithium.

Lithium Treatment Improves Cardiac Dysfunction in Rats Deprived of Rapid Eye Movement Sleep

“…Our recent study revealed that lithium at therapeutic doses reduced the migration and collagen synthesis ability of cardiac fibroblasts through its inhibitory effects on store-operated Ca 2+ entry [ 13 ]. These findings are in line with those of other clinical studies that have suggested the cardioprotective potential of lithium [ 14 , 15 ]. Although heart failure is the primary cause of sudden cardiac death in patients with bipolar disorder [ 16 ], the role of lithium in REM sleep deprivation-induced cardiac dysfunction remains unclear.…”

Association of Lithium Treatment With Reduced Left Ventricular Concentricity in Patients With Bipolar Disorder

“…Existing data indicate that lithium treatment may reduce the risk of cardiovascular diseases in patients with bipolar disorder (BD) 1–3 . Our recent pilot study demonstrated that longer lithium exposure was associated with favorable diastolic function among patients with BD 4 . The findings suggest that lithium treatment may help prevent heart failure in individuals with BD.…”

“…Echocardiography was performed by an experienced board‐certified cardiologist blinded to the clinical data according to our previously published protocol 4,6 . In brief, LV geometric patterns were determined based on the recommendations from the American Society of Echocardiography 7 .…”

“…Data on the clinical characteristics of patients were obtained through interviews and medical records. To estimate medication exposure, we calculated the ratio of drug exposure in relation to bipolar illness chronicity, 3,4 which is the ratio of the total lifetime years of drug treatment to the total number of years since the onset of BD.…”

Long-Term Lithium Therapy: Side Effects and Interactions

“…Taipei’s authors showed that patients who received lithium as the maintenance treatment had significantly lower mean values of left ventricular internal diameters at end-diastole and end-systole, higher mean values of mitral valve E/A ratio, and superior performance of global longitudinal strain than those without lithium treatment. As possible mechanisms, they postulate lithium’s effect on cardiac remodeling involving many signaling pathways as well as its influence on a chemokine, fractalkine [ 47 ].…”