Association of lipids and inflammatory markers with left ventricular wall thickness in patients with bipolar disorder.

BACKGROUND: Individuals with bipolar disorder (BD) face a high risk of heart failure and left ventricular (LV) dysfunction. Despite strong evidence that high LV relative wall thickness (RWT) is a risk marker for heart failure, few studies have evaluated LV RWT and aggravating factors in individuals with BD. METHODS: We recruited 104 participants (52 patients with BD and 52 age- and sex-matched mentally healthy controls) to undergo echocardiographic imaging and biochemistry, high-sensitivity C-reactive protein (hs-CRP), and blood cell count measurements. LV RWT was estimated using the following equation: (2 × LV posterior wall end-diastolic thickness)/LV end-diastolic diameter. Clinical data were obtained through interviews and chart reviews. RESULTS: The BD group exhibited a significantly greater LV RWT (Cohen's d = 0.53, p = 0.003) and a less favorable mitral valve E/A ratio (Cohen's d = 0.54, p = 0.023) and LV global longitudinal strain (Cohen's d = 0.57, p = 0.047) than did the control group. Multiple linear regression revealed that in the BD group, serum triglyceride levels (ß = 0.466, p = 0.001), platelet-to-lymphocyte ratios (ß = 0.324, p = 0.022), and hs-CRP levels (ß = 0.289, p = 0.043) were all significantly and positively associated with LV RWT. LIMITATIONS: This study applied a cross-sectional design, meaning that the direction of causation could not be inferred. CONCLUSIONS: Patients with BD are at a risk of heart failure, as indicated by their relatively high LV RWT. Lipid levels and systemic inflammation may explain this unfavorable association.

Inflammation associated with left ventricular hypertrophy in bipolar disorder: A cross-sectional study.

OBJECTIVE: Inflammation has received increasing attention as a contributor to the pathophysiology of bipolar disorder (BD) and cardiac hypertrophy into heart failure (HF). Accordingly, we chose BD-related inflammatory markers to investigate their relationships with cardiac left ventricular function and structure in BD. METHODS: Sixty physically healthy and euthymic patients with bipolar I disorder were recruited to compare with 50 healthy normal controls. The echocardiography was performed to estimate left ventricular mass index (LVMI) as a parameter of LV hypertrophy (LVH) and left ventricle ejection fraction (LVEF) as a parameter of systolic function. An LVEF above the normal range (>70%) was defined as a hyperdynamic heart. Participants' levels of inflammatory and atherosclerosis-related parameters were measured. RESULTS: Compared with normal controls, BD group had significantly higher rates of LVH (63% vs. 42%) and hyperdynamic heart (32% vs. 2%) and higher mean values of LVMI and LVEF. After adjustment for the effects of BMI and age, multiple regression analyses of BD group showed that the peripheral level of interleukin-8 was positively associated with LVMI and the level of soluble tumor necrosis factor receptor 1 (sTNF-R1) was positively associated with LVEF. CONCLUSIONS: Patients with BD from young adulthood are likely to have LVH with normal LV function and hyperdynamic heart associated with diastolic dysfunction. Low-grade inflammation may underlie the mechanisms of LV hypertrophy and cardiac dysfunction in BD patients.

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

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.

Identification of Patients with Potential Atrial Fibrillation during Sinus Rhythm Using Isolated P Wave Characteristics from 12-Lead ECGs.

Atrial fibrillation (AF) is largely underdiagnosed. Previous studies using deep neural networks with large datasets have shown that screening AF with a 12-lead electrocardiogram (ECG) during sinus rhythm (SR) is possible. However, the poor availability of these trained models and the small size of the retrievable datasets limit its reproducibility. This study proposes an approach to generate explainable features for detecting AF during SR with limited data. We collected 94,224 12-lead ECGs from 64,196 patients from Taipei Medical University Hospital. We selected ECGs during SR from 213 patients before AF diagnosis and randomly selected 247 age-matched participants without AF records as the controls. We developed a signal-processing technique, MA-UPEMD, to isolate P waves, and quantified the spatial and temporal features using principal component analysis and inter-lead relationships. By combining these features, the machine learning models yielded AUC of 0.64. We showed that, even with this limited dataset, the P wave, representing atrial electrical activity, is depicted by our proposed approach. The extracted features performed better than the bandpass filter-extracted P waves and deep neural network model. We provided a physiologically explainable and reproducible approach for classifying patients with AF during SR.

Echocardiographic study of cardiac structure and function in people with bipolar disorder after midlife.

BACKGROUND: Heart failure is the leading cause of mortality in older people with bipolar disorder (BD). Studies examining cardiac structure and function in middle-aged patients with BD by using echocardiography and cardiac strain imaging are scant. METHODS: We recruited 48 patients with bipolar I disorder (BD-I) older than 45 years to undergo conventional and tissue speckle tracking echocardiography. Data of 31 mentally healthy adults older than 45 years were randomly retrieved from the echocardiographic dataset and compared with the data of BD patients. RESULTS: Patients with BD-I had significantly higher mean values of interventricular septal thickness (Cohen's d = 0.83, p = 0.001) and left ventricular internal diameter (Cohen's d = 0.90, p = 0.001) at end-diastole relative to controls. Additionally, BD-I patients exhibited significantly lower mean values of mitral valve E/A ratio (Cohen's d = 0.67, p = 0.007) and a more reduced global longitudinal strain (Cohen's d = 0.72, p = 0.029) than controls. Multiple linear regression revealed that body mass index was negatively correlated with the mitral valve E/A ratio (adjustment R2 = 0.363, p = 0.043) in patients with BD-I. LIMITATIONS: A relatively small sample size may limit generalization. CONCLUSIONS: After midlife, BD patients exhibit cardiac diastolic (low mitral valve E/A ratio) and systolic (reduced global longitudinal strain) dysfunction. High body mass index may play a role in the unfavorable cardiac function in aging patients with BD.

Association of multiple preventive therapies postdischarge and long-term health outcomes after acute myocardial infarction.

BACKGROUND: Statins, beta-blockers, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers have been advocated by guidelines as secondary prevention medications to improve the long-term outcomes of post-acute myocardial infarction (AMI) patients. However, adequate drug adherence has always been challenging, and different treatment regimens may lead to divergent outcomes that remain unclear under current myocardial infarction (MI) care standards. This study investigated the association between use of different preventive regimens post-AMI and patients' long-term outcomes. METHODS: This cohort study used data files from the Taiwan National Health Insurance Research Database. A total of 77 520 people who were hospitalized with AMI between 2002 and 2015 were assessed. On the basis of medication possession ratio (MPR) to individual medications, eight treatment groups were examined in this study. Receiving therapy was defined as MPR ≥40%. We investigated the association between different treatment groups and all-cause mortality in 24 months. RESULTS: Overall, 51 322 patients with ST-elevation MI and 26 198 with non-ST-elevation MI were included in the study. Patients received all three preventive medications show the lowest mortality in 24 months follow-up periods among all treatment groups. Patients who did not usage of any of these three preventive medications had the highest mortality in 24 months (adjusted hazard ratio, 1.78; 95% CI, 1.64-1.93). This mortality rate had the same pattern across the three cohort generations (2002-2005, 2006-2010, and 2011-2015). CONCLUSION: In this large population-based real-world study, usage of three preventive therapies post-MI was associated with the lowest rate of all-cause mortality.

Long-Term Effect of Device-Guided Slow Breathing on Blood Pressure Regulation and Chronic Inflammation in Patients with Essential Hypertension Using a Wearable ECG Device.

BACKGROUND: Hypertension is related to autonomic nervous system (ANS) dysfunction, atherosclerosis and chronic inflammation. The stimulation of baroreflex regulation by slow-breathing exercise may improve the interplay among these systems. The objective of this study was to investigate the effect of device-guided slow breathing on ANS, cardiovascular system and chronic inflammation in hypertensive patients. METHODS: We prospectively collected 36 essential hypertension patients who were requested to practice slow-breathing exercise 5 times per day for 3 months. The breathing exercise was guided by a cellphone app with a wearable electrocardiography device and a rhythm of 6 cycles per minute. Cardiovascular indicators including heart rate variability (HRV), blood pressure, pulse wave velocity and baroreflex indexes were sampled 3 times: at the first visit, and 1 month and 3 months after the intervention. The levels of blood inflammatory biomarkers, including tumor necrosis factor-alpha (TNF-α), interleukin-6, interleukin-1 receptor antagonist and C-reactive protein were also collected at all 3 visits. The longitudinal differences in these variables and their correlations were tested. RESULTS: There was a significant decrease in blood pressure after 1 month of exercise. A significantly continuous decrease in TNF-α was also observed. The baroreflex indexes were significantly increased in the acute intervention of slow-breathing but not in the longitudinal effect. The HRV variables did not show differences with time. There were positive correlations between sympathetic index and TNF-α and galectin-3. CONCLUSIONS: The effect of slow-breathing exercise on blood pressure and chronic inflammation was significant. HRV indexes may also be used to assess chronic inflammation.

Circulating level of microRNA-142-5p is a potential biomarker for predicting in-stent restenosis: a case-control study.

BACKGROUND: Patients who receive percutaneous coronary intervention (PCI) have different chances of developing in-stent restenosis (ISR). To date, no predictable biomarker can be applied in the clinic. MicroRNAs (miRNAs or miRs) play critical roles in transcription regulation, and their circulating levels were reported to have potential as clinical biomarkers. METHODS: In total, 93 coronary stent-implanted patients without pregnancy, liver or renal dysfunction, malignancy, hemophilia, or autoimmune diseases were recruited in this clinical study. All recruited participants were divided into an ISR group (n = 45) and a non-ISR group (n = 48) based on their restenotic status as confirmed by cardiologists at the first follow-up visit (6 months after surgery). Blood samples of all participants were harvested to measure circulating levels of miRNA candidates (miR-132, miR-142-5p, miR-15b, miR-24-2, and miR-424) to evaluate whether these circulating miRNAs can be applied as predictive biomarkers of ISR. RESULTS: Our data indicated that circulating levels of miR-142-5p were significantly higher in the ISR population, and results from the receiver operating characteristic (ROC) curve analysis also demonstrated superior discriminatory ability of miR-142-5p in predicting patients' restenotic status. In addition, circulating levels of miR-15b, miR-24-2, and miR-424 had differential expressions in participants with diabetes, hyperlipidemia, and hypertension, respectively. CONCLUSIONS: The current study revealed that the circulating level of miR-142-5p has potential application as a clinical biomarker for predicting the development of ISR in stent-implanted patients.

The association between carotid atherosclerosis and treatment with lithium and antipsychotics in patients with bipolar disorder.

OBJECTIVES: Patients with bipolar disorder are at high risk of cardiovascular diseases. Among cardiovascular diseases, coronary heart disease and stroke are the leading causes of premature death and both share the pathogenesis of arterial atherosclerosis. Increased carotid intima-media thickness is sensitive for detecting early atherosclerosis and a practical index for predicting cardiovascular diseases. However, few studies investigated carotid intima-media thickness in adults with bipolar disorder. We attempted to determine the factors associated with carotid intima-media thickness in adults with bipolar disorder. METHODS: The euthymic out-patients with bipolar I disorder aged over 20 years were recruited to measure the carotid intima-media thickness value through B-mode carotid ultrasound. Those with any psychiatric disorder, acute or life-threatening medical condition were excluded. All clinical information was obtained by reviewing medical records and directly interviewing patients with reliable others. RESULTS: Of the 106 participants with a mean age of 44.5 years, 40.6% (N = 43) had concurrent cardiovascular/endocrine/metabolic diseases. A multivariate regression indicated that higher assumed daily lithium dosage was significantly associated with a decreased carotid intima-media thickness in the whole sample. In the young subgroup (⩽45 years old, N = 63), higher current daily lithium dosage and lower body mass index were associated with lower carotid intima-media thickness. In those without concurrent cardiovascular/endocrine/metabolic diseases, higher ratio of first-generation antipsychotics exposure in relation to illness chronicity was associated with higher carotid intima-media thickness, after controlling for body mass index or age. CONCLUSION: Lithium treatment may be associated with less progression in carotid intima-media thickness and the reduced risk for atherosclerosis in adults with bipolar disorder, including those with high cardiovascular disease risk. In addition to age and body mass index, antipsychotics may increase carotid intima-media thickness even in the low cardiovascular disease-risk patients.