Cardiovascular Risk Factors and Phenoconversion to Neurodegenerative Synucleinopathies in Idiopathic REM Sleep Behavior Disorder

Several studies have suggested that atherosclerotic diseases and diabetes may be risk factors for α-synucleinopathies. This prospective cohort study evaluated whether cardiovascular diseases and metabolic risk factors alter the rate or type of phenoconversion from idiopathic/isolated REM sleep behavior disorder (iRBD) to parkinsonism or dementia. Polysomnography-confirmed iRBD patients recruited between 2004 and 2020 were followed annually. Baseline history of cardiovascular disorders, hypertension, hypercholesterolemia, and diabetes were compared among patients who developed outcomes versus those who remained outcome-free. No atherosclerotic risk factors were associated with development of α-synucleinopathies. Patients with hypercholesterolemia were somewhat more likely to develop dementia with Lewy bodies rather than Parkinson’s disease.

Does incidental calcium deposition in non-cardiac CT scans predict cardiovascular morbidity and mortality in young adults? A retrospective study

Background The calcium score in cardiac CT scan represents an effective tool in the diagnosis of coronary artery disease. However, few studies have examined the value of incidental arterial calcification (AC) in non-cardiac CT scans, especially in young adults with no prior cardiovascular morbidity. Purpose To evaluate the association between incidental AC and the incidence of cardiovascular events, as well as the association between atherosclerotic risk factors and AC in young adults with no known cardiovascular disease. Methods A retrospective study in patients aged 40–50 years old with no history of cardiovascular disease that underwent chest CT scan between 1.9.2012–31.8.2013 for reasons not related to cardiovascular disease. We assessed the presence of AC in the aorta and coronary arteries and its association with the rates of coronary catheterization for acute coronary syndrome (CCACS), emergency room (ER) visits or hospitalizations for cardiovascular disease and cardiac mortality. Furthermore, we examined the association between atherosclerotic risk factors (hypertension, smoking, hyperlipidemia and diabetes) and AC. Results 308 patients were included in the study, 150 men and 158 women with average follow-up period of 7.2+0.29 years. AC was found in 88 (28.6%) patients. AC was more frequent in men than in women (35% vs. 20.9%, OR=2.18, P=0.006). Patients with AC underwent more CCACS than those without (11.6% vs. 0.5%, OR = 29.1, P=0.0001). Patients with AC had more ER and hospital admissions (33.7% vs. 14.4%, P<0.0001, OR=3). Individuals with hypertension, smoking, and hyperlipidemia exhibited higher rates of AC (OR=2.66, 4, and 1.9, respectively). A statistically significant excess mortality in those with AC was not demonstrated (P=0.076). Conclusion AC appears to be associated with cardiovascular morbidity and increased incidence of CCACS. Primary preventive strategies in patients with AC may reduce cardiovascular morbidity. FUNDunding Acknowledgement Type of funding sources: None.

Associations between continuous glucose monitoring-derived metrics and arterial stiffness in Japanese patients with type 2 diabetes

Background Previous studies have suggested that high mean glucose levels and glycemic abnormalities such as glucose fluctuation and hypoglycemia accelerate the progression of atherosclerosis in patients with type 2 diabetes. Although continuous glucose monitoring (CGM) that could evaluate such glycemic abnormalities has been rapidly adopted, the associations between CGM-derived metrics and arterial stiffness are not entirely clear. Methods This exploratory cross-sectional study used baseline data from an ongoing prospective, multicenter, observational study with 5 years of follow-up. Study participants included 445 outpatients with type 2 diabetes and no history of apparent cardiovascular disease who underwent CGM and brachial-ankle pulse wave velocity (baPWV) measurement at baseline. Associations between CGM-derived metrics and baPWV were analyzed using multivariate regression models. Results In a linear regression model, all CGM-derived metrics were significantly associated with baPWV, but HbA1c was not. Some CGM-derived metrics related to intra-day glucose variability, hyperglycemia, and hypoglycemia remained significantly associated with baPWV after adjusting for possible atherosclerotic risk factors, including HbA1c. Based on baPWV ≥ 1800 cm/s as indicative of high arterial stiffness, multivariate logistic regression found that some CGM-derived metrics related to intra-day glucose variability and hyperglycemia are significantly associated with high arterial stiffness even after adjusting for possible atherosclerotic risk factors, including HbA1c. Conclusions Multiple CGM-derived metrics are significantly associated with baPWV and high arterial stiffness in patients with type 2 diabetes who have no history of apparent cardiovascular disease. These metrics might be useful for identifying patients at high risk of developing cardiovascular disease.

August 2021 - Volume 15, Issue 3 AUTOSPLENECTOMY MAY NOT HAVE AN ATHEROSCLEROTIC BACKGROUND IN SICKLE CELL DISEASES

Background: We tried to understand whether or not there is a significant relationship between autosplenectomy and atherosclerosis in sickle cell diseases (SCD). Methods: All patients with the SCD were included. Results: The study included 434 patients (222 males and 212 females) with similar mean ages in male and female genders (30.8 versus 30.3 years, respectively, p>0.05). Smoking (23.8% versus 6.1%, p<0.001) and alcohol (4.9% versus 0.4%, p<0.001) were higher in males, significantly. Transfused units of red blood cells (RBC) in their lives (48.1 versus 28.5, p=0.000) were also higher in males, significantly. Similarly, disseminated teeth losses (<20 teeth present) (5.4% versus 1.4%, p<0.001), chronic obstructive pulmonary disease (COPD) (25.2% versus 7.0%, p<0.001), ileus (7.2% versus 1.4%, p<0.001), cirrhosis (8.1% versus 1.8%, p<0.001), leg ulcers (19.8% versus 7.0%, p<0.001), digital clubbing (14.8% versus 6.6%, p<0.001), coronary heart disease (CHD) (18.0% versus 13.2%, p<0.05), chronic renal disease (CRD) (9.9% versus 6.1%, p<0.05), and stroke (12.1% versus 7.5%, p<0.05) were all higher in males but not autosplenectomy (50.4% versus 53.3%, p>0.05) in the SCD. Conclusion: SCD are severe inflammatory processes on vascular endothelium, particularly at the capillary level since the capillary system is the main distributor of hardened RBC into the tissues. Although the higher smoking and alcohol-like strong atherosclerotic risk factors and disseminated teeth losses, COPD, ileus, cirrhosis, leg ulcers, digital clubbing, CHD, CRD, and stroke-like obvious atherosclerotic consequences in male gender, autosplenectomy was not higher in them, significantly. In another definition, autosplenectomy may not have an atherosclerotic background in the SCD. Key words: Sickle cell diseases, chronic endothelial damage, atherosclerosis, autosplenectomy, male gender, smoking, alcohol

External iliac artery endofibrosis in an elite female endurance cyclist

External iliac artery endofibrosis is a rare pathology that affects high-level endurance athletes, especially cyclists. Classical symptoms include pain, loss of power, and/or cramp in the affected limb while training at maximal effort. The patient’s lack of atherosclerotic risk factors makes clinical suspicion of arteriopathy challenging. Moreover, the best management of such patients is still a subject of discussion. We report the case of a 36-year-old professional female endurance cyclist who presented with lower extremity pain during training. Right external iliac artery endofibrosis was diagnosed and the patient underwent surgical treatment. At two-months follow-up, she reported significant improvement in symptoms. This case highlights the importance of diagnosing peripheral vascular disease in young patients and athletes, who do not fit the ordinary profile of patients with atherosclerotic risk factors.

Abstract 13080: Clinical Significance of Clonal Hematopoiesis With JAK2V617F in Patients With Cardiovascular Diseases

Background: It becomes increasingly clear that age-related clonal hematopoiesis (CH) is associated with cardiovascular diseases. However, CH with a driver mutation that causes myeloproliferative neoplasm (MPN) is not fully understood. Objective: To determine the clinical relevance of CH with MPN-driving mutations on cardiovascular diseases. Methods: This study prospectively enrolled 832 patients with cardiovascular diseases who did not show any hematological disorders. We examined the presence of the known MPN-driving mutations including JAK2V617F, CALRdel52, CALRins5, MPLW515L, and MPLW515K by an allele-specific polymerase chain reaction. Results: Out of 832 patients, 16 patients (1.9%) exhibited MPN-driving mutations including 15 patients with JAK2V617F (1.8%) and 1 patient with CALRins5 (0.1%). We divided the patients into two groups: vascular diseases including coronary artery disease, stroke, aortic aneurysm, aortic dissection, peripheral artery disease, deep vein thrombosis, and pulmonary thromboembolism (n=462, 55%) and non-vascular diseases (n=370, 45%). The prevalence of JAK2V617F-positive CH was significantly higher in patients with vascular diseases than in those with non-vascular diseases (2.8% vs. 0.5%, P = 0.014). In a multivariable analysis adjusted for known classic-atherosclerotic risk factors (age, male, obesity, smoking, hypertension, diabetes mellitus, dyslipidemia), the presence of JAK2V617F-positive CH was independently associated with vascular diseases (odds ratio, 5.448; P = 0.043). Additionally, peripheral leukocyte IL1B mRNA expressions as well as plasma interleukin-1β concentrations were significantly increased in patients with JAK2V617F-positive CH compared to those without JAK2V617F (P = 0.040 and P = 0.030, respectively). Conclusions: CH with JAK2V617F, but not CALR or MPL mutations, was significantly associated with vascular diseases independently on classic-atherosclerotic risk factors, in relation to interleukin-1β-related inflammatory mechanisms. JAK2V617F is a potential diagnostic and therapeutic target for vascular diseases.

Relationship Between Serum Eicosapentaenoic Acid to Arachidonic Acid Ratio and Atherosclerotic Risk Factors in Patients With Peripheral Artery Disease

Background: The eicosapentaenoic acid to arachidonic acid ratio (EPA/AA) is attracting attention as a risk factor for peripheral artery disease (PAD). However, there have been few studies investigating the relationship between the EPA/AA ratio and atherosclerotic risk factors in patients with PAD. The purpose of the present study was to analyze atherosclerotic risk factors in patients with PAD to identify those factors associated with a low EPA/AA ratio. Methods. The data of patients treated for symptomatic PAD at Tokyo Medical University Hospital and Eniwa Midorino Clinic between April 2014 and March 2018 were retrospectively analyzed. Results. A total of 149 patients were tested for blood levels of n-3 and n-6 polyunsaturated fatty acids, including EPA and AA. 73 patients had a low EPA/AA ratio (<0.4) and 76 patients had a high EPA/AA ratio (≥ 0.4). Univariate analysis showed that older age (≥ 75 years), female sex, smoking history, body mass index (BMI), and hemoglobin A1C (HbA1C) were associated with the low EPA/AA ratio. Multivariable analysis showed that older age (odds ratio [OR], 0.34; 95% confidential interval [CI], 0.15-0.76; p = 0.008), BMI (OR, 0.87; 95% CI, 0.77-0.98; p = 0.027), smoking history (OR, 2.67; 95% CI, 1.09-6.55; p = 0.007), and HbA1C (OR, 0.46; 95% CI, 0.29-0.72; p = 0.020) were independently associated with the low EPA/AA ratio. Conclusions. The EPA/AA ratio was related to existing arteriosclerotic risk factors in patients with PAD; it was positively correlated with older age, increasing BMI, and higher HbA1C, whereas it was negatively correlated with smoking history. These results suggest that the EPA/AA ratio may be closely intertwined with other atherosclerotic risk factors and have an influence on cardiovascular health.