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.

Resistance exercise improves cardiac function and mitochondrial efficiency in diabetic rat hearts.

Metabolic disturbance and mitochondrial dysfunction are a hallmark of diabetic cardiomyopathy (DC). Resistance exercise (RE) not only enhances the condition of healthy individuals but could also improve the status of those with disease. However, the beneficial effects of RE in the prevention of DC and mitochondrial dysfunction are uncertain. Therefore, this study investigated whether RE attenuates DC by improving mitochondrial function using an in vivo rat model of diabetes. Fourteen Otsuka Long-Evans Tokushima Fatty rats were assigned to sedentary control (SC, n = 7) and RE (n = 7) groups at 28 weeks of age. Long-Evans Tokushima Otsuka rats were used as the non-diabetic control. The RE rats were trained by 20 repetitions of climbing a ladder 5 days per week. RE rats exhibited higher glucose uptake and lower lipid profiles, indicating changes in energy metabolism. RE rats significantly increased the ejection fraction and fractional shortening compared with the SC rats. Isolated mitochondria in RE rats showed increase in mitochondrial numbers, which were accompanied by higher expression of mitochondrial biogenesis proteins such as proliferator-activated receptor-γ coactivator-1α and TFAM. Moreover, RE rats reduced proton leakage and reactive oxygen species production, with higher membrane potential. These results were accompanied by higher superoxide dismutase 2 and lower uncoupling protein 2 (UCP2) and UCP3 levels in RE rats. These data suggest that RE is effective at ameliorating DC by improving mitochondrial function, which may contribute to the maintenance of diabetic cardiac contractility.

Best Treatment Strategies With Statins to Maximize the Cardiometabolic Benefits.

Statins are important for preventing adverse cardiovascular events in patients with both high and low risk of vascular disease, by reducing the levels of low-density lipoprotein cholesterol (LDL-C). However, statins dose-dependently increase adverse effects and increase the risk of type 2 diabetes. Previously, it was hypothesized this was caused by to off-target effects, but recent studies demonstrate it is caused by on-target effects. Nonetheless, the American guidelines recommend the use of high-intensity statin therapy, and extend its use to most people at risk of vascular diseases, particularly older people. In contrast, European, Korean, and Japanese committees have expressed concerns about the potential adverse effects of using high-intensity statins for lifelong periods in a large fraction of the population. Patients who have achieved LDL-C levels below currently recommended targets may still experience cardiovascular events, resulting from residual risk. Ezetimibe, PCSK9 inhibitors, inclisiran, and ANGPTL3 antisense oligonucleotides are promising alternative non-statin drugs. Of interest, cross-talk between hypercholesterolemia and the renin-angiotensin-system exists at multiple levels of insulin resistance and endothelial dysfunction. There are still unanswered questions on how to maximize the cardiometabolic benefits of statins in patients. We will discuss the results of randomized clinical trials, meta-analysis, and recent clinicopharmacogenetic studies, and propose practical guidelines to maximize the cardiometabolic benefits while reducing adverse effects and overcoming residual risk.

Gender differences in plaque characteristics of culprit lesions in patients with ST elevation myocardial infarction.

There is limited research on plaque characteristics of ST elevation myocardial infarction (STEMI) patients according to the gender and age. 280 Consecutive STEMI patients who underwent VH-IVUS imaging on culprit before percutaneous coronary intervention (PCI) were enrolled in this study. Women were significantly older than men (69.8 ± 10 vs. 55.9 ± 11.3, p < 0.001). After propensity matching, men had higher plaque burden (79.7 ± 7.8 vs. 73.7 ± 13.0 %, p = 0.010), more fibro-fatty tissue (12.8 ± 9.9 vs. 9.5 ± 6.8 %, p = 0.04) and less dense calcium than women (8.4 ± 5.8 vs. 12.3 ± 8.7 %, p = 0.007). Subgroups dividing by 50, 65, 75 years old, plaque burden was higher in elderly men aged 66-75 years compared to the young men aged less than 50 (75.5 ± 9.2 vs. 68.4 ± 10.1 %, p = 0.012). And middle aged men ranged 51-65 years showed significantly more plaque burden at minimal lumen area site than matched aged women (77.5 ± 8.0 vs. 69.0 ± 17.6 %, p = 0.012). Elderly women aged 66-75 years showed significantly more necrotic core (28.6 ± 7.3 %) and dense calcium (14.9 ± 7.5 %) compared to all the younger or matched subgroups of men. These differences in plaque composition are blunted in the very elderly of men and women aged over 75 years. The findings may explain the gender differences in clinical prognosis in STEMI patients.

Impact of duration and dosage of statin treatment and epicardial fat thickness on the recurrence of atrial fibrillation after electrical cardioversion.

The purpose of this study was to investigate the time-dependent effect of statin treatment and echocardiographic epicardial fat thickness (EFT) on the maintenance of sinus rhythm (SR) in atrial fibrillation (AF) patients after electrical cardioversion (EC). One hundred sixty-three AF patients without previous statin treatment who underwent EC were consecutively enrolled. The maintenance rate of SR after EC (1, 3, 6, and 12 months) as documented by electrocardiogram and EFT were compared between patients with statin treatment (statin group, n = 63) and those without (no statin group, n = 100). There was no significant difference in the maintenance rate of SR between the groups soon after EC (statin group; 85.7 % vs. no statin; 84.8%, p = 0.535), after 1 month (71.0 vs. 59.1%, p = 0.091), and after 3 months (63.2 vs. 50.0%, p = 0.086). However, the maintenance rate of SR was significantly higher in the statin group compared to no statin group (61.8 vs. 42.9%, p = 0.024) after 6 months, and this significant difference persisted up to 12 months of follow up (60.1 vs. 36.4%, p = 0.001). Patients with recurrence showed higher baseline EFT (7.4 ± 2.7 vs. 8.5 ± 3.0 mm, p = 0.014). Multivariate linear regression analysis indicated that EFT, left atrial diameter, high-density lipoprotein cholesterol, statin treatment, and dose were the significant contributors to the maintenance of SR for all periods after EC. Statin treatment and low EFT were associated with a higher maintenance rate of SR in AF patients after EC. Significant benefit of statin was realized 6 months after EC, and this benefit was shown to be maintained over time.

Correlation between Patient-Reported Symptoms and Ankle-Brachial Index after Revascularization for Peripheral Arterial Disease.

Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation between the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months after peripheral revascularization. Mean PAQ summary scores improved significantly three months after revascularization (+49.3 ± 15 points, p < 0.001). PAQ scores relating to patient symptoms showed the largest improvement following revascularization. The smallest increases were seen in reported treatment satisfaction (all p's < 0.001). As expected the ABI of treated limbs showed significant improvement post-revascularization (p < 0.001). ABI after revascularization correlated with patient-reported changes in the physical function and QoL domains of the PAQ. Twenty-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI < 0.15). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI > 0.15 following revascularization. In conclusion, data from the current study suggest a significant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization.

Simvastatin attenuates the oxidative stress, endothelial thrombogenicity and the inducibility of atrial fibrillation in a rat model of ischemic heart failure.

Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF), and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI)-induced heart failure (HF) rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group) and underwent echocardiography, AF induction studies and left atrial (LA) fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX), sarcoplasmic reticulum calcium ATPase (SERCA), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham), which were significantly reduced by simvastatin (p < 0.05 vs. MI). The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.

Prognostic value of creatine kinase-myocardial band isoenzyme elevation following percutaneous coronary intervention: a meta-analysis.

OBJECTIVES: To assess whether different degrees of creatine kinase-myocardial band isoenzyme (CK-MB) elevation after percutaneous coronary intervention (PCI) affect the subsequent risk of death. BACKGROUND: While there is consensus that extensive cardiac enzyme elevation increase mortality significantly, there is uncertainty about the exact clinical impact of smaller CK-MB elevations after PCI. METHODS: The published literature was scanned by formal searches of electronic databases such as PubMed and MEDLINE from January 1999 to October 2011. Risk ratio (RR) was used as summary estimate. RESULTS: Ten studies have been included totaling 48,022 patients who underwent PCI (12,246 patients with CK-MB elevation and 35,776 patients without CK-MB elevation). Mean followup duration for each study ranged from 6 to 48 months. CK-MB elevation >1× the upper limit of normal (ULN) conferred a significant increase in the risk of mortality with an overall RR of 1.74 (95% confidence interval [CI], 1.42 to 2.13, P < 0.001). Compared with patients without CK-MB elevation, there was a dose-response relationship with RR for death being 1.48 (95% CI, 1.25-1.77, P < 0.001) with CK-MB elevation 1 to <3× ULN, 1.71 (95% CI, 1.23-2.37, P = 0.001) with CK-MB elevation 3 to 5× ULN, and 2.83 (95% CI, 1.98-4.04, P < 0.001) with CK-MB elevation ≥ 5× ULN. CONCLUSIONS: Even a small increase in CK-MB levels after PCI is associated with significantly higher risk of late mortality. Monitoring cardiac enzymes after PCI may help predict the long term clinical outcome.

Heart rate reduction with ivabradine prevents thyroid hormone-induced cardiac remodeling in rat.

Ivabradine slows the heart rate (HR) by selectively inhibiting the I(f) current in the sinus node without a negative inotropic effect. We aimed to investigate the effects of ivabradine on thyroid hormone-induced left ventricular (LV) remodeling and ion channel activity in rats. Thirty Sprague-Dawley rats were randomly selected into the groups of control, injection of L-thyroxine (T4, 100 µg/kg/day), and injection of L-thyroxine with ivabradine (T4-Iva, T4 + 10 mg/kg/day). Circumferential (S circ), radial (S rad), and longitudinal (S long) strains were assessed by speckle tracking echocardiography (STE). Myocardial width and fibrosis were assessed from histological LV cross sections, and electrophysiological analysis was done by patch clamp method. In comparison with the control group, the T4 group showed significantly increased HR and LV end-systolic diameter (LVESD), reduced S circ (-16.04 ± 3.95 vs. -7.84 ± 2.98 %, p < 0.001), S rad (20.94 ± 3.81 vs. 40.57 ± 6.70 %, p < 0.001), and S long (-15.26 ± 5.15 vs. -23.83 ± 5.19 %, p < 0.001), despite the 59.5 % increase of average I Ca,L density at 0 mV (13.4 ± 1.2 pA/pF) compared to control group (8.4 ± 0.8 pA/pF). Treatment with ivabradine significantly reduced HR and LVESD, improved SRcirc, S long and SRlong in the T4 group, and the average I Ca,L density at 0 mV in T4-Iva groups (9.9 ± 1.6 pA/pF) was restored to the control level. Morphologically, the T4 group showed significantly increased cardiomyocyte width (25.3 ± 1.89 vs. 18.90 ± 1.14 µm in control, p < 0.001) and fibrosis, which were not significantly changed by ivabradine. In conclusion, selective HR reduction by ivabradine attenuates thyroid hormone-induced reduction of myocardial deformation and altered intracellular Ca(2+) handling without modification of the myocyte hypertrophy with fibrosis in rats.

The predictive value of retinal vascular findings for carotid artery atherosclerosis: are further recommendations with regard to carotid atherosclerosis screening needed?

Vascular retinopathy is the consequence of vascular disease, and the retina is the only place where the arteries can be visualized directly. The purpose of this study was to evaluate the predictive value of retinal vascular findings for carotid artery atherosclerosis. From December 2009 to January 2011, the carotid intima-media thickness (IMT) and total plaque area (TPA) were measured in 179 consecutive patients, who received a fundoscopic examination. The patients were divided into groups as follows: normal retinal artery (normal; n = 44), diabetic retinopathy (DR; n = 25), retinal artery occlusion (RAO; n = 17), retinal vein occlusion (RVO; n = 67), and hypertensive retinopathy (HTN-R; n = 26). The subjects were classified according to the presence of an increased (≥ 1 mm) IMT and plaque. The values of the mean carotid IMT in the patients with vascular retinopathy (DR, 0.87 ± 0.14 mm; RAO, 1.18 ± 0.47 mm; RVO, 0.84 ± 0.14 mm; HTN-R, 0.90 ± 0.20 mm) were significantly increased compared with those in the normal subjects (0.77 ± 0.13 mm). A total 77 of 135 vascular retinopathy patients demonstrated an increased IMT (57 %), and 97 vascular retinopathy patients had carotid artery plaque (72 %). The relative risk of vascular retinopathy in the prediction of an increased IMT and the presence of plaque was 2.79 and 3.95, respectively. Although The TPA was significantly increased in the patients with RAO (1.87 ± 2.67 cm(2)) and RVO (0.27 ± 0.23 cm(2)) compared with the normal subjects (0.18 ± 0.23 cm(2), all Ps < 0.05), there was no significant difference in the ipsilateral carotid IMT and TPA of the affected eye compared with that of the contralateral eye. In conclusion, vascular retinopathy demonstrated a good predictive value in identifying asymptomatic carotid artery atherosclerosis, and this was not confined to the ipsilateral carotid artery of the affected eye. Further recommendations with regard to carotid atherosclerosis screening in patients with vascular retinopathy should be considered.

Left atrial responses to acute right ventricular apical pacing in patients with sick sinus syndrome.

Chronic right ventricular apical (RVA) pacing can lead to an increased risk of heart failure and atrial fibrillation, but the acute effects of RVA pacing on left atrial (LA) function are not well known. Twenty-four patients with sick sinus syndrome and intact intrinsic atrioventricular conduction were included. All patients received dual-chamber pacemaker implants with the atrial lead in the right atrial appendage and the ventricular lead in the right ventricular (RV) apex. Transthoracic standard and strain echocardiography (measured by tissue Doppler imaging and speckle tracking image) were performed to identify functional changes in the left ventricle (LV) and LA before and after 1 hour of RVA pacing. The LA volume index did not change after pacing; however, the ratio of peak early diastolic mitral flow velocity (E) to peak early diastolic mitral annular velocity (Ea) was significantly increased and peak systolic LA strain (Sm), mean peak systolic LA strain rate (SmSR), peak early diastolic LA strain rate (EmSR), and peak late diastolic LA strain rate (AmSR) were significantly reduced after RV pacing. LV dyssynchrony, induced by RV pacing, had a significant correlation with E/Ea, Sm, and SmSR after pacing. E/Ea also had a negative correlation with Sm and SmSR after pacing. Multivariate regression analysis identified LV dyssynchrony and E/Ea as important factors that affect Sm, SmSR, EmSR, and AmSR after acute RVA pacing. Acute RVA pacing results in LA functional change and LV dyssynchrony and higher LV filling pressures reflected by E/Ea are important causes of LA dysfunction after acute RVA pacing.

Carotid arterial stiffness in patients with rheumatoid arthritis assessed by speckle tracking strain imaging: its association with carotid atherosclerosis.

OBJECTIVES: Although a series of trials support the intima-media thickness (IMT) of carotid artery as a good predictor for the cardiovascular events in patients with rheumatoid arthritis (RA), the link between IMT, vascular elastic property and the disease activity of RA is not defined. We investigated the association between carotid atherosclerosis, elastic properties of the carotid arterial wall and clinical parameters of RA. METHODS: One hundred and twenty RA patients and fifty healthy controls were included. Peak systolic global circumferential and posterior radial strain of carotid artery were measured to assess the elastic properties. Beta stiffness index was used as conventional method for the distensibility of the carotid artery. RA activity was assessed by high sensitivity C-reactive protein (hsCRP) and disease activity score with 28 joints (DAS 28) and health assessment questionnaire (HAQ). RESULTS: Carotid plaques were more common in RA patients. RA patients with plaques were older and had an increased mean IMT, hsCRP, DAS 28, and longer disease duration compared with those without plaques. Peak systolic global circumferential and posterior radial strain were congruent with ß stiffness index, and significantly lower in the RA group. Age, disease duration, hsCRP, DAS 28 showed significant correlations with mean IMT and parameters of carotid elastic property. CONCLUSIONS: Carotid atherosclerosis was more common in RA patients, and carotid arterial stiffness had significant correlation with disease duration and disease activity of RA. Speckle tracking strain imaging is a comparative method for the assessment of elastic properties of carotid artery of RA patients.

Sodium bicarbonate therapy for the prevention of contrast-induced acute kidney injury ­ a systematic review and meta-analysis ­.

BACKGROUND: Sodium bicarbonate has been postulated to prevent contrast-induced acute kidney injury (CI-AKI) by various mechanisms, although the reports are conflicting. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and the Cochrane databases for randomized controlled trials that compared a sodium chloride with a sodium bicarbonate hydration regimen with regard to CI-AKI. Data across 19 clinical trials consisting of 3,609 patients were combined. Preprocedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of CI-AKI (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.36-0.86; P=0.008). Stratified analyses by the type of contrast medium suggested lower odds of CI-AKI with sodium bicarbonate in studies using low-osmolar contrast media (OR 0.40; 95% CI 0.23-0.71, P=0.002) compared with those using the iso-osmolar agents (OR 0.76; 95% CI 0.41-1.43; P=0.40). No significant difference in the rates of postprocedural death (OR 0.49; 95% CI 0.23-1.04; P=0.06) and the requirement for renal replacement therapy (OR 0.94; 95% CI 0.46-1.91; P=0.86) was observed. However, we found significant changes in serum bicarbonate and potassium levels after sodium bicarbonate infusion. CONCLUSIONS: This updated meta-analysis demonstrates that sodium bicarbonate-based hydration is superior to sodium chloride in preventing CI-AKI of patients undergoing exposure to iodinated contrast media.

Cross-cultural adaptation and validation of the Peripheral Artery Questionnaire: Korean version for patients with peripheral vascular diseases.

The Peripheral Artery Questionnaire (PAQ), as developed in US English, is a validated scale to evaluate the health status of patients with peripheral artery disease (PAD). The aim of this study was to translate the PAQ into Korean and to evaluate its reliability and validity. A multi-step process of forward-translation, reconciliation, consultation with the developer, back-translation and proofreading was conducted. The test-retest reliability was evaluated at a 2-week interval using the intra-class correlation coefficient (ICC). The validity was assessed by identifying associations between Korean PAQ (KPAQ) scores and Korean Health Assessment Questionnaire (KHAQ) scores. A total of 100 PAD patients were enrolled: 63 without and 37 with severe claudication. The reliability of the KPAQ was adequate, with an ICC of 0.71. There were strong correlations between KPAQ's subscales. Cronbach's alpha for the summary score was 0.94, indicating good internal consistency and congruence with the original US version. The validity was supported by a significant correlation between the total KHAQ score and KPAQ physical function, stability, symptom, social limitation and quality of life scores (r = -0.24 to -0.90; p < 0.001) as well as between the KHAQ walking subscale and the KPAQ physical function score (r = -0.55, p < 0.001). Our results indicate that the KPAQ is a reliable, valid instrument to evaluate the health status of Korean patients with PAD.

A meta-analysis of randomized controlled trials appraising the efficacy and safety of cilostazol after coronary artery stent implantation.

OBJECTIVES: To evaluate the impact of cilostazol on the angiographic and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) with stents and treated with aspirin and thienopyridine. METHODS: A total of 11 randomized controlled trials including 8,525 patients comparing triple antiplatelet therapy (aspirin, thienopyridine and cilostazol) with standard dual antiplatelet therapy were included in the analysis. The primary end points were in-segment late loss and angiographic restenosis at angiographic follow-up. Secondary end points included mortality, stent thrombosis, target lesion revascularization (TLR) and major adverse cardiac events (MACE). RESULTS: Triple antiplatelet therapy was associated with a significant reduction in late loss [weighted mean difference 0.14, 95% confidence interval (CI) 0.08-0.20; p < 0.001] and angiographic restenosis [odds ratio (OR) 0.58, 95% CI 0.48-0.71; p < 0.001]. Addition of cilostazol to dual antiplatelet therapy was associated with a significant reduction in TLR (OR 0.56, 95% CI 0.41-0.77; p < 0.001) and MACE (OR 0.72, 95% CI 0.60-0.86; p < 0.001) with no differences in mortality (p = 0.29), stent thrombosis (p = 0.60) or bleeding episodes (p = 0.77). CONCLUSIONS: Cilostazol in addition to dual antiplatelet therapy appears to be effective in reducing the risk of restenosis and repeat revascularization after PCI without any significant benefits for mortality or stent thrombosis.

Irbesartan prevents myocardial remodeling in experimental thyrotoxic cardiomyopathy.

This study evaluated the effects of irbesartan and propranolol on thyroid hormone (TH)-induced cardiac functional and structural remodeling. A rat model of thyrotoxicosis was established by daily intraperitoneal injections of L-thyroxine (T(4), 100 µg/kg) for 4 weeks. Forty Sprague-Dawley rats were randomly divided into four groups (n = 10 each): control group, T(4) group (T(4) alone), T(4) plus irbesartan group (T(4)-Irb, 30 mg/kg), and T(4) plus propranolol group (T(4)-Pro, 0.5mg/mL of drinking water). Cardiac chamber size and functional parameters were measured by echocardiography and cardiomyocyte diameter. Heart rate (HR) and cardiac fibrosis were determined. T(4) alone showed significantly increased HR and cardiomyocyte width (25.0 ± 1.77 vs. 18.8 ± 0.84 µm, P < 0.001) with fibrosis, reduced left ventricle (LV) longitudinal strain (S(long); -16.0 ± 6.27 vs. -22.7 ± 5.19 %, P < 0.001) compared with control. When compared with T(4) alone, T(4)-Irb showed significantly improved LV S(long) (-21.4 ± 1.84 vs. -16.0 ± 6.27 %, P =0.017) and reduced cardiomyocyte width (21.0 ± 1.0 vs. 25.0 ± 1.77 µm, P =0.002) with comparable HR (458.4 ± 24.3 vs. 486.6 ± 30.1 bpm, P = 0.086). However, T(4)-Pro showed significantly reduced HR with improved LV S(long) without alteration of cardiomyocyte width and fibrosis compared with T(4) alone. In conclusion, renin-angiotensin system (RAS) blocking by irbesartan could significantly attenuate TH-induced cardiac structural and functional remodeling. However, HR reduction by propranolol could not alternate structural remodeling, which may implicate the RAS as having an important role in thyrotoxic cardiomyopathy beyond tachycardia.

Impact of obstructive sleep apnea on the global myocardial performance beyond obesity.

We aimed to assess the impact of obstructive sleep apnea (OSA) on the left ventricular (LV) function independent of obesity using the myocardial performance index (Tei index) and the global longitudinal LV strain (GLS) and its reversibility after surgery. Twenty-five newly diagnosed OSA patients, normal weight (n = 15) and obese (body mass index [BMI] ≥ 25; n = 20) controls without OSA were enrolled and underwent transthoracic echocardiographic evaluation. The OSA and obese groups had a significantly comparable increased BMI and LV chamber dimension, prolonged isovolumic relaxation time, reduced early mitral filling velocity, and increased late mitral filling velocity and Tei index as compared to the normal weight group. However, GLS was significantly reduced only in the OSA group (-16.5 ± 1.9%) as compared to the normal weight group (-20.6 ± 2.0%, P < 0.001) and obese group (-19.1 ± 2.5%, P < 0.001). As a treatment, 13 of 25 patients underwent surgical modification, and the follow-up echocardiogram revealed significantly improved Tei index and GLS as compared to baseline (0.37 ± 0.06 and -18.9 ± 3.3% vs. 0.42 ± 0.04 and -16.3 ± 2.4%, P = 0.006 and 0.031, respectively), which was comparable to the obese controls. A reduction in the apnea-hypopnea index had a significant effect on the improvement in the GLS (r = 0.73, P < 0.001). LV systolic and diastolic function significantly deteriorated in the patients with OSA beyond obesity, and an improvement in the LV function was observed within 6 months after the surgical modification. GLS is considered to be one of the parameters that can be used in the early detection of LV systolic dysfunction in patients with OSA and a normal ejection fraction.

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.

Impact of gestational hypertension on left ventricular function and geometric pattern.

BACKGROUND: The effect of gestational hypertension on left ventricular (LV) function in previously normotensive young women has not been evaluated. METHODS AND RESULTS: A total of 106 gestational hypertensive women (GHW, 32.3 ± 4.2 years) and 93 normotensive pregnant women (NPW, 30.2 ± 4.4 years) were enrolled. Transthoracic echocardiography, including 2-dimensional strain echocardiography, was done and myocardial performance (Tei index), LV mass index (LVMI), and relative wall thickness (RWT) were analyzed. GHW had significantly increased wall thickness (interventricular septum, 9.5 ± 0.9 mm vs. 8.8 ± 1.0 mm, P < 0.001; posterior wall, 9.0 ± 1.1 mm vs. 8.5 ± 1.1 mm, P = 0.007; and RWT, 0.39 ± 0.06 vs. 0.35 ± 0.05, P = 0.02), higher LVMI (95.6 ± 17.3g/m² vs. 86.1 ± 14.5g/m², P = 0.03), longer isovolumetric relaxation time (117.7 ± 18.2 ms vs. 82.3 ± 12.6 ms, P = 0.003), lower E/A ratio (1.00 ± 0.29 vs. 1.27 ± 0.33, P = 0.002), and higher Tei index (0.48 ± 0.23 vs. 0.33 ± 0.13, P = 0.003) compared to NPW. Global longitudinal LV strain, representing LV systolic function, was also significantly reduced in GHW compared with NPW (-17.6 ± 2.95% vs. -21.2 ± 2.14%, P = 0.02). A total of 62% of GHW (n = 66) had abnormal geometry, of whom, 42 (40%) had eccentric hypertrophy (EH). A total of 93% of NPW (n = 86) had normal geometry, and only 7 NPW (7%) had abnormal geometry. CONCLUSIONS: GHW had aggravated diastolic and longitudinal systolic dysfunction. GHW had increased LVMI with the abnormal geometric pattern of EH. The reversibility of these morphological and functional impairments after delivery needs to be clarified.

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.