Effects of luseogliflozin on arterial properties in patients with type 2 diabetes mellitus: The multicenter, exploratory LUSCAR study.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the occurrence of cardiovascular and renal complications in patients with type 2 diabetes mellitus (T2DM) and represent guideline-recommended therapy in this indication. However, precise mechanisms underlying the beneficial cardiovascular effects of SGLT2 inhibitors are not fully understood. This study investigated the effects of the SGLT2 inhibitor, luseogliflozin, on arterial properties and home blood pressure (BP) in patients with T2DM. This multicenter, single-arm study enrolled adults with T2DM, glycosylated hemoglobin (HbA1c) 6.5%-8.9% in the previous 4 weeks, and an indication for new/additional antidiabetic therapy. Luseogliflozin 2.5 mg/d was given for 12 weeks. Primary outcome was change in cardio-ankle vascular index (CAVI) from baseline to Week 4 and Week 12. Home and office BP, BP variability, and metabolic parameters were secondary endpoints. Forty-seven patients (mean age 63.5 ± 10.7 years) treated with luseogliflozin were included in the full analysis set. CAVI did not change significantly from baseline (mean [95% confidence interval] 8.67 [8.37-8.97]) to Week 12 (8.64 [8.38-8.91]; P = .750), but there were significant reductions from baseline in morning home BP, HbA1c, body weight, body mass index, and serum uric acid levels during luseogliflozin therapy. The reduction in morning home systolic BP was ≥ 5 mm Hg and was independent of baseline BP and BP control status. In conclusion, there was no change in arterial stiffness (based on CAVI) during treatment with luseogliflozin, but changes in BP and metabolic parameters were consistent with the known beneficial effects of SGLT2 inhibitors in T2DM.

Sleep-disordered breathing predicts cardiovascular events and mortality in hemodialysis patients.

BACKGROUND: Sleep-disordered breathing (SDB), characterized by repetitive apnea and hypopnea during sleep, is a risk factor for cardiovascular disease. However, the links between SDB and cardiovascular events in hemodialysis (HD) patients have not been clearly evaluated. METHODS: We followed the clinical outcome of 94 HD patients, who underwent overnight pulse oximetry on dialysis day. The SDB group was defined as 3% oxygen desaturation index (ODI) over five events per hour, and the others were the normal group. The primary outcome was cardiovascular events and death. We used Kaplan-Meier curve and Cox proportional hazard model for survival analyses. RESULTS: Forty-four patients (46.8%) were classified into the SDB group. Body mass index, diabetes mellitus, 3% ODI and Epworth sleepiness scale were significantly higher, and duration of dialysis, Kt/V, normalized protein catabolism rate and hemoglobin were lower in the SDB group than in the normal group. During a median 55 months of follow-up, Kaplan-Meier analysis revealed that the SDB group had a significantly higher rate of cardiovascular events and all-cause mortality than the normal group. Age, cardiothoracic ratio, serum albumin and 3% ODI were predictors of cardiovascular events and all-cause mortality at univariate Cox regression analysis. In the adjusted analysis, SDB is an independent predictor of increased cardiovascular events (hazard ratio 3.10; 95% confidence interval (CI), 1.35-7.12; P = 0.008) and all-cause mortality (hazard ratio 2.81; 95% CI, 1.07-7.41; P = 0.037). CONCLUSIONS: SDB is an independent risk factor for cardiovascular events and mortality in HD patients. Effective and earlier treatment for these patients is needed to improve clinical outcome.

A case of infected aortic aneurysm with possible intramural abscess resolved through discharge into the vascular lumen without surgical intervention.

Infected aortic aneurysms are difficult to treat and, in the absence of aortic resection, are almost always fatal. We report a case of an infected aortic aneurysm cured by antibiotic treatment alone. In this case, the intramural abscess was supposed to be naturally resolved by the discharge of pus into the vascular lumen and infection was suppressed by the antibiotic treatment.

Can ischemic stroke be caused by acute reduction of blood pressure in the acute phase of cardiovascular disease?

Acute-phase cardiovascular disease (CVD) frequently presents with markedly elevated blood pressure (BP) levels and often requires fairly rapid lowering of BP. On the other hand, aggressive lowering of systemic BP to the point that the cerebral BP decreases below a certain threshold may result in ischemic stroke. The authors retrospectively studied 192 consecutive patients with CVD who had markedly elevated BP and end-organ damage. Ischemic stroke was noted in 12 of these patients during BP-lowering therapy. The incidence of ischemic stroke did not differ significantly between a standard BP-lowering group, in which the target BP reduction was within the parameters of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines, and a rapid BP-lowering group, in which the target BP was below these guidelines (7.1% vs 2.6%, respectively; P=.27, not significant). In stepwise multiple regression analysis, diabetes mellitus (beta=0.203, P=.008) and acute pulmonary edema (beta=0.228, P=.003) remained significant factors associated with the incidence of stroke. Thus, acute pulmonary edema and diabetes were the most important factors related to ischemic stroke during BP reduction in patients with marked elevations of BP regardless of the rapidity of BP lowering.

Hyponatremic seizure associated with acute respiratory infection.

A 66-year-old woman was admitted to our hospital because of vomiting and appetite loss. For the 2 days prior to admission, she had a cold, which had developed into acute viral bronchitis on admission. Because laboratory data on admission showed hyponatremia, intravenous infusion of Ringer's lactate solution was started. However, generalized seizures appeared, and she developed a coma on the day of admission. Her plasma antidiuretic hormone (ADH) level was high in the context of a low serum osmolality on the second hospital day. The infusion rate was increased, and the patient's consciousness level returned to normal. However, her normalized serum Na level declined again as she drank much water to reduce throat discomfort. As the throat discomfort caused by the throat inflammation improved with azulene gargling, her water intake was reduced, and the serum Na concentration returned to normal. Thus, polydipsia caused by a throat inflammation partially contributed to hyponatremia in this patient. We note that increased ADH secretion has been reported in adults with acute respiratory infection. Therefore, we concluded that polydipsia caused by the throat inflammation, plus increased ADH secretion, resulted in hyponatremia in this patient. We should pay attention to the behavior of drinking extra fluid in patients with acute respiratory infections.

Systemic lupus erythematosus initially manifesting as acute pericarditis complicating with cardiac tamponade : a case report.

A 23-year-old woman was admitted with progressive shortness of breath. Echocardiography showed a large volume of pericardial effusion, which indicated cardiac tamponade. Yellowish and puriform fluid with increased white blood cell count (neutrophil dominant) was aspirated, but antibiotics were ineffective. Further examination revealed the presence of positive anti ds-DNA antibody, anti SS-A antibody and anti Sm antibody, resulting in a diagnosis of systemic lupus erythematosus. Her condition was smoothly improved by predonisolone administration. Cardiac tamponade is a rare initial manifestation of systemic lupus erythematosus.

[Cholesterol pericarditis identified by increased cardiothoracic ratio on chest radiography: a case report].

A 72-year-old man with no symptoms was admitted to our hospital to investigate increased cardiothoracic ratio on chest radiography. There were no specific physical findings but the cardiac sound was weak. Electrocardiography showed low voltage in all leads. Thyroid function was within normal limits. Echocardiography revealed massive pericardial effusion. Pericardiocentesis was performed, and 1,800ml of gold paint-like opaque fluid was drained. Microscopic examination revealed cholesterol crystals, so the diagnosis was cholesterol pericarditis. Cytologic examination revealed no malignant cells, and no bacteria was cultured. Mycobacterium tuberculosis was not amplified using the polymerase chain reaction method of pericardial fluid. Further analysis showed reduction of apo-B in the pericardial fluid, suggesting involvement in the precipitation of cholesterol.

Evidence for proteasomal degradation of Kv1.5 channel protein.

BACKGROUND: The voltage-gated potassium channel Kv1.5 plays a critical role in the maintenance of the membrane potential. While protein degradation is one of the major mechanisms for the regulation of channel functions, little is known on the degradation mechanism of Kv1.5. METHODS AND RESULTS: Kv1.5 was expressed in COS cells and its degradation, intracellular localization, and channel activities were assessed by pulse-chase analysis, immunofluorescence, and patch clamp techniques, respectively. Expressed Kv1.5 had a half-life time of approximately 6.7 h, which was prolonged by the proteasome inhibitors of MG132, ALLN, proteasomal inhibitor 1, or lactacystine, but not by a lysosomal inhibitor chloroquine. MG132 increased the protein level of Kv1.5, as well as the level of its ubiquitinated form in a dose-dependent manner. Similar effects of MG132 on endogenous Kv1.5 were seen in cultured rat atrial cells. Within a cell, Kv1.5 was mainly localized in both the endoplasmic reticulum and Golgi apparatus. MG132 increased the immunoreactivity of Kv1.5 in these compartments and also increased Ik(ur) currents through the cell-surface Kv1.5. Pretreatment with either brefeldin A or colchicine abolished MG132-induced increase in Ik(ur) currents. CONCLUSION: Kv1.5 is degraded by the proteasome. The inhibition of the proteasome increased Ik(ur) currents secondary to stabilization of the channel protein in the endoplasmic reticulum/Golgi apparatus.

Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study.

BACKGROUND: Cardiovascular events occur most frequently in the morning hours. We prospectively studied the association between the morning blood pressure (BP) surge and stroke in elderly hypertensives. METHODS AND RESULTS: We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed and silent cerebral infarct was assessed by brain MRI and who were followed up prospectively. The morning BP surge (MS) was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. During an average duration of 41 months (range 1 to 68 months), 44 stroke events occurred. When the patients were divided into 2 groups according to MS, those in the top decile (MS group; MS > or =55 mm Hg, n=53) had a higher baseline prevalence of multiple infarcts (57% versus 33%, P=0.001) and a higher stroke incidence (19% versus 7.3%, P=0.004) during the follow-up period than the others (non-MS group; MS <55 mm Hg, n=466). After they were matched for age and 24-hour BP, the relative risk of the MS group versus the non-MS group remained significant (relative risk=2.7, P=0.04). The MS was associated with stroke events independently of 24-hour BP, nocturnal BP dipping status, and baseline prevalence of silent infarct (P=0.008). CONCLUSIONS: In older hypertensives, a higher morning BP surge is associated with stroke risk independently of ambulatory BP, nocturnal BP falls, and silent infarct. Reduction of the MS could thus be a new therapeutic target for preventing target organ damage and subsequent cardiovascular events in hypertensive patients.

Regional upregulation of Kv2.1-encoded current, IK,slow2, in Kv1DN mice is abolished by crossbreeding with Kv2DN mice.

Overexpression of a truncated Kv1.1 channel transgene in the heart (Kv1DN) resulted in mice with a prolonged action potential duration due to marked attenuation of a rapidly activating, slowly inactivating potassium current (I(K,slow1)) in ventricular myocytes. Optical mapping and programmed electrical stimulation revealed inducible ventricular tachycardia due to spatial dispersion of repolarization and refractoriness. Here we show that a delayed rectifier with slower inactivation kinetics (I(K,slow2)) was selectively upregulated in Kv1DN cardiocytes. This electrical remodeling was spatially restricted to myocytes derived from the apex of the left ventricle. Biophysical and pharmacological studies of I(K,slow2) indicate that it resembles Kv2-encoded currents. Northern blot analyses and real-time PCR revealed upregulation of Kv2.1 transcript in Kv1DN mice. Crossbreeding of Kv1DN mice with mice expressing a truncated Kv2.1 polypeptide (Kv2DN) eliminated I(K,slow2). In summary, our data indicate that the spatially restrictive upregulation of Kv2.1-encoded currents underlies the increased dispersion of the repolarization observed in Kv1DN mice.