Effect of a fixed-dose combination of Telmisartan/S-amlodipine on circadian blood pressure compared with Telmisartan monotherapy: TENUVA-BP study.

BACKGROUND: This study evaluated the circadian efficacy of a telmisartan 40 mg/S-amlodipine 2.5 mg fixed-dose combination (Telmisartan40/S-Amlodipine2.5) compared to telmisartan 80 mg (Telmisartan80) in patients with essential hypertension who did not respond to 2-4 weeks' treatment with telmisartan 40 mg. METHODS: Eligible patients with essential hypertension (clinic mean sitting systolic blood pressure [MSSBP] ≥140 mmHg, or ≥ 130 mmHg in those with diabetes mellitus or chronic kidney disease) were randomly assigned to Telmisartan40/S-Amlodipine2.5 or Telmisartan80 for 8 weeks. All patients underwent ambulatory BP monitoring (ABPM) at baseline and 8 weeks later. Primary endpoints were changes in mean 24-h SBP and DBP on 24-h ABPM from baseline after 8 weeks. Secondary endpoints were changes in daytime, nighttime, and morning SBP and DBP, and clinic MSSBP and MSDBP. RESULTS: A total of 316 Korean patients were enrolled, 217 patients were randomized to treatment, and 192 patients completed the study. Compared to Telmisartan80, Telmisartan40/S-Amlodipine2.5 showed significantly better reductions in 24-h mean SBP and DBP after 8 weeks. Telmisartan40/S-Amlodipine2.5 also significantly reduced secondary endpoints compared to Telmisartan80. Among 15 adverse events (7 [Telmisartan40/S-Amlodipine2.5] and 8 [Telmisartan80]), there were five adverse drug reactions; 14 events were mild, and none were identified with significant between-group differences. CONCLUSIONS: Telmisartan40/S-Amlodipine2.5 was tolerable and more effective than Telmisartan80 in lowering 24-h mean ambulatory BP in patients with essential hypertension not responding adequately to Telmisartan40. Our findings support the fact that the combination of S-amlodipine with telmisartan is more appropriate than increasing the dose of telmisartan monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02231788 . Registered 4 September 2014.

Efficacy and safety of nebivolol in Korean patients with hypertension by age and sex: a subanalysis from the BENEFIT-KOREA study.

BACKGROUND: BENEFIT-KOREA (BEnefits after 24 weeks of NEbivolol administration For essential hypertensIon patients wiTh various comorbidities and treatment environments in Korea) study, an observational study in South Korea, demonstrated the efficacy and safety of nebivolol in Asian patients with essential hypertension with and without comorbidities in real-world settings. We present a subanalysis of the efficacy and safety of nebivolol across age and sex in the BENEFIT-KOREA cohort. METHODS: Adult South Korean patients with essential hypertension participated in the prospective, single-arm, open, observational BENEFIT-KOREA study; 3011 patients received nebivolol as monotherapy or add-on therapy. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and pulse rate at 12 and 24 weeks were evaluated. Participants were divided into three age groups-young males and females: < 50 years; middle-aged males and females: ≥50 years to < 70 years; and older males and females: ≥70 years. RESULTS: The mean age of study participants was 63.5 ± 12.9 years; majority were between 50 and 69 years of age and 40.4% were females. A significant decrease was observed in mean SBP, DBP, and pulse rate from baseline at 12 and 24 weeks in males and females across all age groups analyzed (all P < 0.001 vs. baseline), with no significant difference in mean reduction in SBP and DBP from baseline between sex within the age groups. Majority of reported adverse events were mild. The incidence of adverse events was lower in young participants versus middle-aged and older participants. CONCLUSIONS: Our subanalysis from the real-world BENEFIT-KOREA study in Asian patients with essential hypertension demonstrated the efficacy and safety of once-daily nebivolol across age groups with no between-sex differences. TRIAL REGISTRATION: Name of the registry: clinicaltrials.gov. TRIAL REGISTRATION NUMBER: NCT03847350 . Date of registration: February 20, 2019 retrospectively registered.

Changes in QRS Duration Are Associated with a Therapeutic Response to Sacubitril-valsartan in Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Recent studies have demonstrated that angiotensin receptor neprilysin inhibitors (ARNIs) can reverse the cardiac remodeling effects that occur in heart failure with reduced ejection fraction (HFrEF). These studies have also suggested that ARNIs have favorable effects on ventricular dyssynchrony. We assessed the changes in QRS duration associated with ARNIs in patients with HFrEF. METHODS: We retrospectively investigated patients with HFrEF (defined by a left ventricular ejection fraction [LVEF] ≤ 35%) who were treated with ARNIs for at least six months. We divided the patients into QRS shortening and non-QRS shortening groups according to their electrocardiogram (ECG) findings. We also compared changes in echocardiographic parameters between the groups. RESULTS: A total of 68 patients with HFrEF were included (mean age: 62.5 years, 74.6% male). Twenty-one patients had significant ischemic heart disease (IHD). Thirty-five patients exhibited QRS-duration shortening on follow-up ECGs (mean change: -7.8 msec), and 33 patients showed no changes or increased QRS duration (mean change: 5.1 msec). The QRS shortening group exhibited significant improvement in LVEF (12.5 ± 15.3% vs. 1.7 ± 9.5%; p < 0.001) when compared with the non-QRS shortening group. The QRS shortening group also had significantly lower LV end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD) and LV mass index (LVMI) than did the non-QRS shortening group. The change in QRS duration was significantly correlated with the change in LVEF (r = -0.329, p = 0.011) and LVESD (r = 0.298, p = 0.022). CONCLUSIONS: Among patients with HFrEF treated with ARNIs, the QRS shortening group showed favorable LV systolic function recovery, and reversal of cardiac remodeling compared to those of the non-QRS shortening group. Change in the QRS duration, which reflects LV synchrony, may be associated with response to ARNIs in patients with HFrEF.

BH4 activates CaMKK2 and rescues the cardiomyopathic phenotype in rodent models of diabetes.

Diabetic cardiomyopathy (DCM) is a major cause of mortality/morbidity in diabetes mellitus patients. Although tetrahydrobiopterin (BH4) shows therapeutic potential as an endogenous cardiovascular target, its effect on myocardial cells and mitochondria in DCM and the underlying mechanisms remain unknown. Here, we determined the involvement of BH4 deficiency in DCM and the therapeutic potential of BH4 supplementation in a rodent DCM model. We observed a decreased BH4:total biopterin ratio in heart and mitochondria accompanied by cardiac remodeling, lower cardiac contractility, and mitochondrial dysfunction. Prolonged BH4 supplementation improved cardiac function, corrected morphological abnormalities in cardiac muscle, and increased mitochondrial activity. Proteomics analysis revealed oxidative phosphorylation (OXPHOS) as the BH4-targeted biological pathway in diabetic hearts as well as BH4-mediated rescue of down-regulated peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) signaling as a key modulator of OXPHOS and mitochondrial biogenesis. Mechanistically, BH4 bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and activated downstream AMP-activated protein kinase/cAMP response element binding protein/PGC-1α signaling to rescue mitochondrial and cardiac dysfunction in DCM. These results suggest BH4 as a novel endogenous activator of CaMKK2.

Factors Associated with Low Awareness of Heart Failure in the General Population of Korea.

BACKGROUND AND OBJECTIVES: Factors associated with low heart failure (HF) awareness have not been well-evaluated. This study was conducted to find out which demographic features would be associated with low HF awareness in the general population of Korea. METHODS: A telephone interview was conducted with 1,032 adults (58 years and 50.6% were male) across the country. Based on answer to 15 questions about HF, we scored from 0 to 15 points (mean, 7.53±2.75; median, 8; interquartile range, 6-9). A score of <8 was defined as low HF awareness, and a score of ≥8 was defined as high HF awareness. RESULTS: A total of 478 subjects (46.3%) had low HF awareness. HF awareness scores were 5.18±1.85 and 9.55±1.50 in subjects of low and high HF awareness groups, respectively. Subjects with low HF awareness were older, more female-dominant, more diabetic, lower educational and house hold income levels, and more frequently living in rural areas, compared to those with high HF awareness (p<0.05 for each). In multivariable logistic regression analyses, older age (≥67 years: odds ratio [OR], 1.61; 95% confidence interval [CI], 1.16-2.19; p=0.004), female sex (OR, 1.33; 95% CI, 1.02-1.73; p=0.034) and low educational level (high school graduate or less vs. college graduate: OR, 2.38; 95% CI, 1.75-3.22; p<0.001) were significantly associated with low HF awareness even after controlling for potential confounders. CONCLUSIONS: Older age, female sex, and lower level of education were independently associated with low HF awareness in the general Korean population. More attention and education are needed for these vulnerable groups to improve HF awareness.

A randomized, double-blind clinical trial to evaluate the efficacy and safety of a fixed-dose combination of amlodipine/rosuvastatin in patients with dyslipidemia and hypertension.

This multicenter, randomized, double-blind, parallel-group phase III clinical trial aimed to investigate the efficacy and safety of a rosuvastatin + amlodipine combination compared with that of rosuvastatin or amlodipine monotherapy in hypertensive patients with dyslipidemia. A total of 106 patients of 15 institutions in Korea were randomly assigned to 1 of 3 treatment groups: rosuvastatin 20 mg + amlodipine 10 mg, amlodipine 10 mg, or rosuvastatin 20 mg. After 8 weeks of treatment, the mean ± SD of change in mean sitting systolic blood pressure (msSBP) was -22.82 ± 12.99 mm Hg in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. The percentage of patients whose msSBP decreased ≥20 mm Hg or msDBP decreased ≥10 mm Hg was also highest in this group (74.29%). The mean ± SD percentage change in low-density lipoprotein cholesterol (LDL-C) level from baseline after 8 weeks was -52.53% ± 11.21% in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. More patients in the rosuvastatin + amlodipine group achieved their target LDL-C goal at 8 weeks, compared with the other treatment groups (97.14%). No serious adverse events or adverse drug reactions were observed in all groups. In hypertensive patients with dyslipidemia, combination treatment with rosuvastatin 20 mg + amlodipine 10 mg effectively reduced blood pressure and LDL-C levels while maintaining safety.

Effects of High-Intensity Interval Training Versus Moderate-Intensity Continuous Training on Epicardial Fat Thickness and Endothelial Function in Hypertensive Metabolic Syndrome.

Background: Hypertension is common in patients with metabolic syndrome (MS), and it is an important risk factor for cardiovascular-related morbidity and mortality. Compared to moderate-intensity continuous training (MICT), high-intensity interval training (HIIT) is considered a time-efficient exercise strategy for cardiometabolic health. We compared the effects of HIIT and MICT on epicardial fat thickness (EFT) and endothelial function in patients with hypertensive MS. Methods: In total, 34 participants with hypertensive MS (mean age: 50.9 ± 7.9 years) were randomized to either the HIIT (n = 17) or MICT (n = 17) group. In the HIIT group, participants performed for 3 min at 40% heart-rate reserve (HRR), which was alternated with 3 min at 80% HRR, whereas participants in the MICT group performed at 60% of HRR thrice a week for 8 weeks. EFT was measured with echocardiography, and endothelial function was determined by quantifying endothelial progenitor cells (EPCs), nitric oxide (NO), and flow-mediated dilation (FMD). Results: After exercise training, patients in both the groups showed significantly decreased EFT (P < 0.001 and P < 0.01) and improved FMD (P < 0.001 and P < 0.01). NO (P < 0.05) and EPCs (CD34/KDR, P < 0.01; CD34/CD117, P < 0.05; CD34/CD133, P < 0.05) were significantly improved in the HIIT group, but not in the MICT group. In addition, HIIT had a greater effect than MICT on FMD (group difference, P < 0.05) and EFT (group difference, P < 0.05). Conclusions: Compared to MICT, HIIT seems to better improve FMD and EFT. This finding suggests that HIIT could be more effective than MICT in improving endothelial function in patients with hypertensive MS.

Effects of exergaming in postmenopausal women with high cardiovascular risk: A randomized controlled trial.

OBJECTIVE: Recently, exergames have been used an exercise modality as aerobic fitness activities. However, evidence of its effectiveness on cardiovascular (CV)-related risk factors remain unclear. HYPOTHESIS: We evaluate the effects of exergaming on CV-related risk factors compared with traditional aerobic exercise in high CV risk patients. METHODS: Sixty-five postmenopausal women with high CV risk were randomized among exergame (n = 22), treadmill (n = 22), and control (n = 21) groups. The exergame group was engaged in the running-based exergame using Exer Heart and the treadmill group walked or jogged on a treadmill. Cardiorespiratory fitness, flow-mediated dilation, endothelial progenitor cells (EPCs), epicardial fat thickness, metabolic parameters, and anthropometric parameters were measured in patients before and 12 weeks after the training. RESULTS: Exergaming significantly improved VO2 peak (P < .001; different from control, P < .05), flow-mediated dilation (P < .001; different from control, P < .05), EPCs (CD34/CD117+ , P < .01). Treadmill exercise was effective at improving VO2 peak (P < .01; different from control, P < .05), flow-mediated dilation (P < .05), EPCs (CD34/CD117+ , P < .01; different from control P < .05). Epicardial fat thickness decreased after both exercise programs (exergame, P < .01; treadmill, P < .01; no different from control). CONCLUSION: Exergaming showed similar effects to traditional aerobic exercise in improving cardiorespiratory fitness and endothelial function in postmenopausal women with high CV risk. These findings suggest that the exergames may serve as an alternative to conventional aerobic exercises for prevention and treatment in high CV risk patients.

Heart failure awareness in the Korean general population: Results from the nationwide survey.

BACKGROUND: For a better heart failure outcome, it is fundamental to improve the awareness of heart failure at the general population level. We conducted this study to identify the current status of awareness of heart failure in the Korean general population. METHODS: This cross-sectional nationwide survey recruited a total of 1,032 participants aged 30 years or older, based on a stratification systematic sampling method. A 23-item questionnaire was surveyed through telephone interviews. RESULTS: Although 80% of the participants had heard of heart failure, 47% exactly defined what heart failure is. A minority of participants correctly recognized the lifetime risk of developing heart failure (21%) as well as the mortality (16%) and readmission risk (18%) of heart failure and the cost burden of heart failure admission (28%). Regarding preferred treatment options, 71% of the participants chose a treatment option that could improve the quality of life. Approximately two-thirds of the participants agreed that current medical treatment could reduce mortality and improve the quality of life. More than half of the participants (59%) thought that heart failure patients should live quietly and reduce all physical activities. Across survey items, we found a lower awareness state in the elderly groups and people at lower income and educational levels. CONCLUSIONS: The current awareness status of heart failure in the Korean general population is still low. Proactive educational efforts should be made to improve public awareness with special attention to individuals with lower disease awareness.

Exergaming Improves Executive Functions in Patients With Metabolic Syndrome: Randomized Controlled Trial.

BACKGROUND: Recent studies indicate that participation in exercise-related games can improve executive function, attention processing, and visuospatial skills. OBJECTIVE: The aim of this study was to investigate whether exercise via exergaming (EXG) can improve executive function in patients with metabolic syndrome (MetS). METHODS: A total of 22 MetS patients were recruited and randomly assigned to an EXG group or a treadmill exercise (TE) group. The reaction time (RT) and electrophysiological signals from the frontal (Fz), central (Cz), and parietal (Pz) cortices were collected during a Stroop task after 12 weeks of exercise. RESULTS: During the Stroop congruence (facilitation) judgment task, both the EXG and TE groups showed significantly faster RT after 12 weeks of exercise training. For N200 amplitude, the EXG group demonstrated significantly increased electrophysiological signals from the Fz and Cz cortices. These changes were significantly larger in the EXG group than in the TE group. Separately, for the P300 amplitude, the EXG groups presented significantly increased electrophysiological signals from the Fz, Cz, and Pz cortices, whereas the TE group showed significantly increased electrophysiological signals from the Cz and Pz cortices only. During the Stroop incongruence (interference) judgment task, both the EXG and TE groups showed significantly faster RT. For P300 amplitude, the EXG group had significantly increased electrophysiological signals from the Fz and Cz cortices only, whereas the TE group had significantly increased electrophysiological signals from the Fz, Cz, and Pz cortices. CONCLUSIONS: EXG improves executive function in patients with MetS as much as normal aerobic exercise does. In particular, a unique benefit of EXG beyond increased aerobic capacity is the improved selective attention among cognitive functions. Thus, EXG could be recommended to someone who needs to improve their brain responses of concentration and judgment as well as physical fitness. TRIAL REGISTRATION: ClinicalTrials.gov NCT04015583; https://clinicaltrials.gov/ct2/show/NCT04015583.

Strategies to Overcome Residual Risk During Statins Era.

At present, atherosclerosis is one of the most important field in clinical and research medicine. Because it is closely related to cardiovascular (CV) and endocrine disorders such as coronary artery disease, cardiometabolic disorders, much research on how to manage atherosclerosis has been performed. The low-density lipoprotein cholesterol (LDL-C) concentration has been established as an independent risk factor for developing atherosclerosis, and considerable effort has been committed to educating both physicians and the general public on the importance of lowering LDL-C with statins. Although statins have already significantly improved CV outcomes, patients with LDL-C target levels achieved by intense statin therapy still have significant remaining CV risk. Statins already play a central role in managing hyperlipidemia; however, residual risk with statins is an important field of managing remaining CV risk. Recent studies have suggested residual cholesterol and inflammation risks in causing CV events. In the current review, we will discuss residual risk and suggest strategies to overcome it in the statins era.

Tetrahydrobiopterin enhances mitochondrial biogenesis and cardiac contractility via stimulation of PGC1α signaling.

Tetrahydrobiopterin (BH4) shows therapeutic potential as an endogenous target in cardiovascular diseases. Although it is involved in cardiovascular metabolism and mitochondrial biology, its mechanisms of action are unclear. We investigated how BH4 regulates cardiovascular metabolism using an unbiased multiple proteomics approach with a sepiapterin reductase knock-out (Spr-/-) mouse as a model of BH4 deficiency. Spr-/- mice exhibited a shortened life span, cardiac contractile dysfunction, and morphological changes. Multiple proteomics and systems-based data-integrative analyses showed that BH4 deficiency altered cardiac mitochondrial oxidative phosphorylation. Along with decreased transcription of major mitochondrial biogenesis regulatory genes, including Ppargc1a, Ppara, Esrra, and Tfam, Spr-/- mice exhibited lower mitochondrial mass and severe oxidative phosphorylation defects. Exogenous BH4 supplementation, but not nitric oxide supplementation or inhibition, rescued these cardiac and mitochondrial defects. BH4 supplementation also recovered mRNA and protein levels of PGC1α and its target proteins involved in mitochondrial biogenesis (mtTFA and ERRα), antioxidation (Prx3 and SOD2), and fatty acid utilization (CD36 and CPTI-M) in Spr-/- hearts. These results indicate that BH4-activated transcription of PGC1α regulates cardiac energy metabolism independently of nitric oxide and suggests that BH4 has therapeutic potential for cardiovascular diseases involving mitochondrial dysfunction.

Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia: A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study.

PURPOSE: The aim of this study was to evaluate the blood pressure-lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia. METHODS: This study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non-HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A1c. Tolerability of combination therapy was compared with other monotherapy groups. FINDINGS: The percentage changes of LDL-C were -48.6% (from 157.2 to 80.1 mg/dL) in the RSV group and -49.8% (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non-HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A1c had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, -8.7% [37.6%] vs 17.1% [53.1%]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group. IMPLICATIONS: Once-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261.

Heart rate recovery and blood pressure response during exercise testing in patients with microvascular angina.

BACKGROUND: Angina pectoris with a normal coronary angiogram, termed microvascular angina (MVA), is an important clinical entity; however, its causes remain unclear. Autonomic dysfunction is one of the possible causes. Therefore, this study aimed to investigate parasympathetic dysfunction assessed by heart rate recovery (HRR) and increased sympathetic activity assessed by exaggerated blood pressure (BP) response (EBPR) to exercise in MVA. METHODS: The study participants were consecutive patients with anginal chest pain who underwent both coronary angiography with an ergonovine provocation test and a treadmill exercise test between January 2008 and February 2015. Patients with significant coronary artery disease (coronary artery stenosis ≥50%) or significant coronary artery spasm (≥90%) were excluded. Based on the treadmill exercise test, patients were categorized into the microvascular angina (MVA) group (patients with uniform ST depression ≥1 mm) and the control group. HRR was defined as peak heart rate minus heart rate after a 1 min recovery; blunted HRR was defined as ≤12 beats/min. EBPR was defined as a peak exercise systolic BP ≥210 mmHg in men and ≥ 190 mmHg in women. These parameters were compared between patients with MVA and the controls. RESULTS: Among the 970 enrolled patients (mean age 53.1 years; female 59.0%), 191 (20.0%) were diagnosed with MVA. In baseline characteristics, the MVA group had older participants, female predominance, and a higher prevalence of hypertension. The MVA group showed significantly lower HRR 1 min (24.9 ± 15.9 vs. 31.3 ± 22.7, p <  0.001) compared with the control group. Moreover, the proportion of EBPR was significantly higher in the MVA group than in the control group (21.5% vs. 11.6%, p <  0.001). Multivariable logistic regression analysis showed that age (odds ratio (OR), 1.045; 95% confidence interval (CI), 1.026-1.064; p <  0.001), HRR 1 min (OR, 0.990; 95% CI, 0.982-0.999; p = 0.022), and EBPR (OR, 1.657; 95% CI, 1.074-2.554; p = 0.022) were independently associated with MVA. CONCLUSION: HRR and EBPR were associated with MVA, which suggests a link between MVA and autonomic dysregulation.

Inflammatory and metabolic mechanisms underlying the calcific aortic valve disease.

Although calcific aortic stenosis is a very common disease with major adverse cardiovascular events and healthcare costs, there are no effective medical interventions to delay or halt its progression. Cardiometabolic risk factors, including smoking and male sex, are linked to aortic stenosis. Emerging studies have identified important regulatory roles for immunological and inflammatory responses, including oxidized lipids, various cytokines, and biomineralization. Recent clinical and experimental studies in atherosclerosis and osteoporosis have demonstrated that oxidative stress and oxidized lipids decrease bone formation in the skeletal system while they increase bone formation in the cardiovascular system. Multidisciplinary factors contribute to vascular calcification, including inflammation and metabolic regulation of osteogenesis in the cardiovascular system via similar signaling pathways as bone formation. Calcific aortic valve disease (CAVD) is no longer considered a simple passive process of calcium deposition that occurs with advanced age. Biomineralization in CAVD is a complex, regulated process that involves valvular, circulating, bone marrow-derived cells, macrophage heterogeneity and genetic factors along with biochemical and mechanical factors. The current review will discuss the recently discovered important role of inflammation, metabolic risk factors, and molecular and cellular mechanisms that promote CAVD, as well as the link between osteogenic signals in the skeletal and cardiovascular systems. This may inform future therapeutic strategies for CAVD progression.

Epicardial Fat Thickness and Free Fatty Acid Level are Predictors of Acute Ischemic Stroke with Atrial Fibrillation.

BACKGROUND: Increased epicardial fat is known to be associated with the presence and chronicity of atrial fibrillation (AF). Free fatty acids (FFAs) are major components of epicardial fat; however, their potential association with AF in ischemic stroke has not been investigated. We aimed to assess the performance of echocardiographic epicardial fat thickness (EFT) and plasma FFA level in identifying patients with ischemic stroke and AF. METHODS: We enrolled a total of 214 consecutive patients (mean age, 66.8 ± 12.3 years; 39.7% women) diagnosed with acute ischemic stroke between March 2011 and June 2014. The patients were divided into two groups: ischemic stroke with AF (n = 35, 16.4%) and ischemic stroke without AF (n = 179, 83.6%). RESULTS: The ischemic stroke with AF group showed significantly higher serum FFA level (1379.7 ± 717.5 vs. 757.8 ± 520.5 uEq/L, p < 0.0001) and EFT (6.5 ± 1.2 vs. 5.3 ± 1.2 mm, p < 0.001) than the group without AF. Multivariable logistic regression analysis demonstrated that age (odds ratio [OR], 1.112), serum FFA level (OR, 1.002), and EFT (OR, 1.740) were independently associated with the ischemic stroke group with AF. EFT and FFA significantly improved the goodness-of-fit and discriminability of the simple regression model including age as a covariate (log likelihood difference, 21.35; p < 0.001; c-index difference, 17.9%; p < 0.001). CONCLUSIONS: High EFT and serum FFA level were associated with ischemic stroke in patients with AF. Echocardiographic EFT and serum FFA level can play a significant role in identifying ischemic stroke with AF.

Clinical and electrocardiographic characteristics for prediction of new-onset atrial fibrillation in asymptomatic patients with atrial premature complexes.

BACKGROUNDS: Identification of precursors of atrial fibrillation (AF) may lead to early detection and prevent associated morbidity and mortality. Atrial premature complexes (APCs) are commonly seen in healthy subjects. However, there was limited data about the clinical and electrocardiographic (ECG) characteristics for prediction of new-onset AF in asymptomatic patients with APCs in the long-term follow up. METHODS: The Kosin University (No. 2014-02-04) 24-h holter monitoring, echocardiography, ECG database were reviewed from 2008 to 2016 to identify new- onset AF in patients with APCs. We analyzed demographic and clinical features and the nature of the APCs by ECG according to new-onset AF in those patients. RESULTS: Among 652 patients who underwent 24-h holter monitoring, 226 (34.4%) patients had new-onset AF. There was no difference of the baseline characteristics between new-onset AF group and non-AF group. In univariate analysis, hypertension (HTN), renal failure (CRF), high APC burdens, fastest APC running heart rate (HR), minimal HR, left ventricular ejection fraction (LVEF), left atrial volume index, peak mitral flow velocity of the early rapid filling wave and tricuspid regurgitation grade were significantly associated with new-onset AF. In multivariate analysis, higher APCs burden (P = 0.047), higher fastest APCs running HR (P = 0.034) and lower minimal HR (P = 0.025) were independent risk factors for new-onset AF in asymptomatic patients with APCs. CONCLUSION: Higher APCs burden, higher fastest APCs running HR and lower minimal HR were associated with new-onset AF in asymptomatic patients with APCs in the long-term follow up.

Association of frequent premature ventricular complex >10% and stroke-like symptoms without a prior diagnosis of stroke or transient ischemic attack.

INTRODUCTION: Premature ventricular complex (PVCs) detected from long-term ECG recordings have been associated with an increased risk of ischemic stroke. However, there was limited data about the association between high PVCs burdens (>10%) and stroke-like symptoms without a prior diagnosis of stroke or transient ischemic attack in the long-term follow up. METHODS: The Kosin University 24-hours holter monitoring, echocardiography, electrocardiogram (ECG) database were reviewed from 2013 to 2015 to identify patients with frequent PVCs (>10%). We compared the long-term clinical outcomes between the patients with frequent PVCs (>10%) and control group without PVC. RESULTS: Among 572 patients who underwent 24-hours holter monitoring, finally, 373 consecutive patients (mean age; 59.5 ±â€¯15.8 years, 45.2% male) were enrolled. Among them, 203(54.4%) patients had high PVCs burdens (>10%). There was no difference of the baseline characteristics. In the long term follow-up, PVCs burden was not associated with PVCs -related symptoms (P = 0.210). In univariate analysis, female, non-sustained ventricular tachycardia (VT), sinus QRS duration, PVC coupling interval (CI), post- PVC CI, and late precordial R-wave transition of PVCs were associated with PVCs-related symptoms. In multivariate analysis, non-sustained VT (P = 0.022) and late precordial R-wave transition of PVCs (P = 0.044) were independent risk factors for PVCs-related stroke-like symptoms with frequent idiopathic PVCs > 10%. CONCLUSION: High PVCs burdens (>10%) were associated with and stroke-like symptoms without a prior diagnosis of stroke or transient ischemic attack in the long-term follow up, suggesting more intensive medical therapy with close clinical follow-up will be required.

Impact of periodontitis as representative of chronic inflammation on long-term clinical outcomes in patients with atrial fibrillation.

Objectives: Relationship between atrial fibrillation (AF) and inflammation was shown in previous studies. However, there was limited data about the association between the periodontitis and AF in the long-term follow-up. The aim of this study was to evaluate the impact of periodontitis on long-term clinical outcomes in patients with AF. Methods: The Kosin University echocardiography, ECG and periodontitis database were reviewed from 2013 to 2015 to identify patients with AF. Those patients were divided into two groups according to the presence of periodontitis and clinical events including any arrhythmic attack, thromboembolic and bleeding and death were collected during a median of 18 months. Results: Among 227 patients with AF, 47 (20.7%) patients had periodontitis. Major adverse cardiac events (MACE) were significantly higher in patients with periodontitis compared with those without periodontitis (p<0.001). Arrhythmias including AF, atrial tachycardia, atrial premature beat, ventricular tachycardia and ventricular premature beat also occurred in 44 (93.6%) patients, which was higher significantly higher incidence in patients with periodontitis than in those without periodontitis (p<0.001). In univariate analysis, age, CHA2DS2-VASc, left atrial volume index (LAVi) and periodontitis were significantly associated with arrhythmic events and MACE including bleeding events, thromboembolic events, arrhythmic events and mortality. In multivariate analysis, LAVi (p=0.005) and periodontitis (p<0.001) were independent risk factors for arrhythmic events and periodontitis (p<0.001) for MACE at the long-term follow-up. Conclusions: The periodontitis as representative of chronic inflammation was an independent predictor of arrhythmic events and MACE in patients with AF.