Histopathological characteristics of the arrhythmogenic right ventricular cardiomyopathy presenting the electrocardiographic characteristics with Brugada syndrome.

INTRODUCTION: The histopathological characteristics of the overlapping disease states of Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been fully elucidated. METHODS: A 71-year-old man showed coved-type ST-segment elevation with the right precordial leads, and the echocardiography demonstrated right ventricular (RV) dilatation. After 11 months, he died of a polymorphic VT storm. RESULTS: The pathological tissue demonstrated fibrofatty degeneration in the free wall of the RV outflow tract based on the heart autopsy. CONCLUSION: The overlapping disease states of BrS and ARVC showed histopathological characteristics consistent with ARVC.

Autopsy evaluation of the implantation site of a His bundle pacing lead demonstrating selective capture.

Evaluations of His bundle pacing (HBP) lead location at autopsy examination have been rarely reported. We report an autopsy case of a 98-year-old man who underwent HBP implantation due to atrioventricular block and heart failure. Although selective HBP was achieved with an acceptable threshold, the stimulus-to-QRS interval was relatively longer without correction of the right bundle-branch block. A macroscopic examination revealed that the HBP lead was inserted on the ventricular side passing through the anteroseptal commissure of the tricuspid valve. Transthyretin cardiac amyloidosis may affect the distal conduction system resulting in a long stimulus-to-QRS interval during selective HBP.

Atypical Fast-Slow Atrioventricular Nodal Reentrant Tachycardia Incorporating a "Superior" Slow Pathway: A Distinct Supraventricular Tachyarrhythmia.

BACKGROUND: The existence of an atypical fast-slow (F/S) atrioventricular nodal reentrant tachycardia (AVNRT) including a superior (sup) pathway with slow conductive properties and an atrial exit near the His bundle has not been confirmed. METHODS AND RESULTS: We studied 6 women and 2 men (age, 74 ± 7 years) with sup-F/S-AVNRT who underwent successful radiofrequency ablation near the His bundle. Programmed ventricular stimulation induced retrograde conduction over a superior SP with an earliest atrial activation near the His bundle, a mean shortest spike-atrial interval of 378 ± 119 milliseconds, and decremental properties in all patients. sup-F/S-AVNRT was characterized by a long-RP interval; a retrograde atrial activation sequence during tachycardia identical to that over a sup-SP during ventricular pacing; ventriculoatrial dissociation during ventricular overdrive pacing of the tachycardia in 5 patients or atrioventricular block occurring during tachycardia in 3 patients, excluding atrioventricular reentrant tachycardia; termination of the tachycardia by ATP; and a V-A-V activation sequence immediately after ventricular induction or entrainment of the tachycardia, including dual atrial responses in 2 patients. Elimination or modification of retrograde conduction over the sup-SP by ablation near the right perinodal region or from the noncoronary cusp of Valsalva eliminated and confirmed the diagnosis of AVNRT in 4 patients each. CONCLUSIONS: sup-F/S-AVNRT is a distinct supraventricular tachycardia, incorporating an SP located above the Koch triangle as the retrograde limb, that can be eliminated by radiofrequency ablation.

Regional Differences in Frequency of Warfarin Therapy and Thromboembolism in Japanese Patients With Non-Valvular Atrial Fibrillation　- Analysis of the J-RHYTHM Registry.

BACKGROUND: The proportion of patients with atrial fibrillation (AF) treated with anticoagulation varies from country to country. In Japan, little is known about regional differences in frequency of warfarin use or prognosis among patients with non-valvular AF (NVAF). METHODS AND RESULTS: In J-RHYTHM Registry, the number of patients recruited from each of 10 geographic regions of Japan was based on region population density. A total of 7,406 NVAF patients were followed up prospectively for 2 years. At baseline, significant differences in various clinical characteristics including age, sex, type of AF, comorbidity, and CHADS2score, were detected among the regions. The highest mean CHADS2score was recorded in Shikoku. Frequency of warfarin use differed between the regions (P<0.001), with lower frequencies observed in Hokkaido and Shikoku. Baseline prothrombin time international normalized ratio differed slightly but significantly between the regions (P<0.05). On univariate analysis, frequency of thromboembolic events differed among the regions (P<0.001), with the highest rate seen in Shikoku. An inverse correlation was detected between frequency of thromboembolic and of major hemorrhagic events (P=0.062). On multivariate analysis, region emerged as an independent risk for thromboembolism. CONCLUSIONS: Thromboembolic risk, frequency of warfarin use, and intensity and quality of warfarin treatment differed significantly between geographic regions of Japan. Region was found to be an independent predictor of thromboembolic events. (Circ J 2016; 80: 1548-1555).

Pseudo-postpacing interval of diastolic potential after entrainment pacing of remote bystander pathway in reentrant ventricular tachycardia.

After entrainment pacing, the postpacing interval of a diastolic potential may be misinterpreted if the distal tip of the ablation catheter captures a remote bystander pathway adjacent to the critical isthmus of a complex reentrant circuit in a structurally diseased heart. We discuss this possible pitfall of entrainment mapping of reentrant ventricular tachycardia, observed after a healed myocardial infarction.

Effects of azelnidipine on uric acid metabolism in patients with essential hypertension.

PURPOSE: To examine effects of a long-acting calcium channel blocker (CCB) azelnidipine on uric acid metabolism in hypertensive patients. METHODS: Azelnidipine was administered to 72 patients at a daily dose of 8 mg or 16 mg. In 22 cases out of the 72 patients, a different CCB was switched to azelnidipine. Blood pressure was measured and biochemical parameters of blood and urine were evaluated before and 2-3 months after the administration. RESULTS: Azelnidipine significantly decreased both systolic and diastolic blood pressure and the heart rate. It decreased both serum urate levels and the urinary uric acid to creatinine ratio (Uur/Ucr), but did not affect the uric acid clearance to creatinine clearance ratio (Cur/Ccr). Azelnidipine decreased both Uur/Ucr and Cur/Ccr in patients with Uur/Ucr ≥ 0.5 or ≥ 0.34, although it did not change these clearance parameters in patients with Uur/Ucr <0.5 or <0.34. Azelnidipine decreased the serum urate levels and Uur/Ucr in hyperuricemic patients with uric acid levels ≥ 7.0 mg/dL in males and ≥ 6.0 mg/dL in females. It did not change these parameters in normouricemic patients with serum urate levels <7.0 mg/dL in males and <6.0 mg/dL in females. Azelnidipine decreased Uur/Ucr and Cur/Ccr in hyperuricemic patients with normal or over excretion of uric acid, although it did not change these clearance parameters in hyperuricemic patients with uric acid hypoexcretion. CONCLUSIONS: Azelnidipine decreased the serum urate acid levels and Uur/Ucr, and this response was most prominent in hyperuricemic patients or patients with normal and over excretion of uric acid.

Ridge-related reentry: a variant of perimitral atrial tachycardia.

INTRODUCTION: The ridge between the left pulmonary veins (PV) and the left atrial appendage composes part of the lateral mitral isthmus (LMI). Following circumferential PV isolation and LMI linear ablation for the treatment of atrial fibrillation (AF), a critical pathway might develop over the ridge leading to a ridge-related reentry (RRR). METHODS AND RESULTS: Out of 61 patients who underwent circumferential PV isolation appended by LMI ablation, 5 patients developed RRR. The diagnosis of RRR was based on (1) macro-reentrant atrial tachycardia involving the septum, anterior and inferior wall of the left atrium; (2) slow conduction along the ridge; (3) wide-split double potentials in the ventricular aspect of the LMI were identified with the coronary sinus (CS) electrodes. RRR was investigated with electroanatomical mapping and entrainment mapping and catheter ablation was carried out in all patients. The mean cycle length (CL) of RRR was 312 ± 82 milliseconds and the PPIs at the left atrial septum, inferior and anterior wall during RRR were 10 ± 6, 12 ± 8, 9 ± 5 milliseconds longer than the RRR CL. The interval of the double potentials recorded in the CS electrodes crossing the LMI was 164 ± 38 milliseconds during RRR and the PPI on the LMI near the mitral annulus was 57 ± 10 milliseconds longer than the RRR CL. Catheter ablation was performed anatomically by targeting the ridge and successfully terminated RRR. CONCLUSION: After circumferential PV isolation and ablation for LMI in patients with AF, RRR can develop by utilizing the surviving myocardial tissue of the ridge as a critical pathway.

Reciprocal control of hERG stability by Hsp70 and Hsc70 with implication for restoration of LQT2 mutant stability.

RATIONALE: The human ether-a-go-go-related gene (hERG) encodes the α subunit of the potassium current I(Kr). It is highly expressed in cardiomyocytes and its mutations cause long QT syndrome type 2. Heat shock protein (Hsp)70 is known to promote maturation of hERG. Hsp70 and heat shock cognate (Hsc70) 70 has been suggested to play a similar function. However, Hsc70 has recently been reported to counteract Hsp70. OBJECTIVE: We investigated whether Hsc70 counteracts Hsp70 in the control of wild-type and mutant hERG stability. METHODS AND RESULTS: Coexpression of Hsp70 with hERG in HEK293 cells suppressed hERG ubiquitination and increased the levels of both immature and mature forms of hERG. Immunocytochemistry revealed increased levels of hERG in the endoplasmic reticulum and on the cell surface. Electrophysiological studies showed increased I(Kr). All these effects of Hsp70 were abolished by Hsc70 coexpression. Heat shock treatment of HL-1 mouse cardiomyocytes induced endogenous Hsp70, switched mouse ERG associated with Hsc70 to Hsp70, increased I(Kr), and shortened action potential duration. Channels with disease-causing missense mutations in intracellular domains had a higher binding capacity to Hsc70 than wild-type channels and channels with mutations in the pore region. Knockdown of Hsc70 by small interfering RNA or heat shock prevented degradation of mutant hERG proteins with mutations in intracellular domains. CONCLUSIONS: These results indicate reciprocal control of hERG stability by Hsp70 and Hsc70. Hsc70 is a potential target in the treatment of LQT2 resulting from missense hERG mutations.

Target international normalized ratio values for preventing thromboembolic and hemorrhagic events in Japanese patients with non-valvular atrial fibrillation: results of the J-RHYTHM Registry.

BACKGROUND: Target anticoagulation levels for warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF) are unclear. METHODS AND RESULTS: Of 7,527 patients with NVAF, 1,002 did not receive warfarin (non-warfarin group), and the remaining patients receiving warfarin were divided into 5 groups based on their baseline international normalized ratio (INR) of prothrombin time (≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0). Patients were followed-up prospectively for 2 years. Primary endpoints were thromboembolic events (cerebral infarction, transient ischemic attack, and systemic embolism), and major hemorrhage requiring hospital admission. During the follow-up period, thromboembolic events occurred in 3.0% of non-warfarin group, but at lower frequencies in the warfarin groups (2.0, 1.3, 1.5, 0.6, and 1.8%/2 years for INR values of ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0059). Major hemorrhage occurred more frequently in warfarin groups (1.5, 1.8, 2.4, 3.3, and 4.1% for INR values ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0041) than in non-warfarin group (0.8%/2 years). These trends were maintained when the analyses were confined to patients aged ≥70 years. CONCLUSIONS: An INR of 1.6-2.6 is safe and effective at preventing thromboembolic events in patients with NVAF, particularly patients aged ≥70 years. An INR of 2.6-2.99 is also effective, but associated with a slightly increased risk in major hemorrhage. (UMIN Clinical Trials Registry UMIN000001569)

The characteristics and efficacy of catheter ablation of focal atrial tachycardia arising from an epicardial site.

BACKGROUND: Although epicardial structures around the atrium such as adipose tissue possess arrhythmogenicity, little is known about atrial tachycardias (ATs) originating from epicardial sites (Epi-ATs). This study aimed to elucidate the prevalence, characteristics, and outcome after radiofrequency catheter ablation (RFCA) of Epi-ATs and to reveal the association between Epi-ATs and the epicardial structures. METHODS: The electrocardiographic, electrophysiologic, and anatomical properties and results of RFCA were analyzed in 42 patients with a total of 49 ectopic ATs. RESULTS: Six Epi-ATs (12%) were observed in six patients (14%). Four of six were respiratory cycle-dependent ATs and one was a swallowing-induced AT. The Epi-AT origins were adjacent to a pulmonary vein (five cases) and vein of Marshall (one case). A Valsalva maneuver or atropine infusion to define the arrhythmia mechanism affected the appearance of the Epi-ATs. The congruity rate between epicardial adipose tissue and the AT origin was significantly higher (100% vs. 44%, p = .045), and the epicardial adipose tissue volume of the atrium was significantly larger (104.1 vs. 64.6 ml, p = .04) in the Epi-AT group. Endocardial RFCA targeting the AT foci resulted in acute success in five of five cases. However, electrical isolation including of the AT foci resulted in acute failures (two of three cases) or a recurrence (one of one case). CONCLUSIONS: Six Epi-ATs were associated with thoracic veins and epicardial arrhythmogenic structures. The main cause provoking the Epi-ATs was associated with autonomic nerve activity.

Identification, isolation and characterization of HCN4-positive pacemaking cells derived from murine embryonic stem cells during cardiac differentiation.

BACKGROUND: Development of biological pacemaker is a potential treatment for bradyarrhythmias. Pacemaker cells could be extracted from differentiated embryonic stem (ES) cells based on their specific cell marker hyperpolarization-activated cyclic nucleotide-gated (HCN)4. The goal of this study was to develop a method of identification, isolation, and characterization of pacemaking cells derived from differentiated ES cells with GFP driven by HCN4 promoter. METHODS AND RESULTS: Polymerase chain reaction (PCR) screening and southern blot analysis revealed that HCN4p-EGFP trans-gene was stably integrated into the chromosome of mouse AB1 ES cells. RT-PCR and immunostaining results showed similar expression of the specific cardiac pacemaker markers of the HCN4p-EGFP ES cells and its parental AB1 ES cell lines. Although HCN4p-EGFP trans-gene may have slight effect on the general mesodermal differentiation, it had no effect on the pluripotency of ES cells, on the transcription of cardiac specific factors and cardiac contractile proteins, and on the capability of ES cells to differentiate into pacemaker cells. Electrophysiological study indicated that HCN4p-GFP-positive cells revealed the spontaneous action potential, which was slowed by the treatment with 2 mM Cs(+), and expressed the hyperpolarization-activeted cation current I(f) encoded by HCN4 gene. CONCLUSION: By the approach of using stable transfectant of HCN4p-EGFP gene, the identification, isolation, and characterization of ES cell-derived pacemaking cells could be carried out.

[Calcium antagonists: current and future applications based on new evidence. The mechanisms on lowering serum uric acid level by calcium channel blockers].

In hypertensive subjects, their serum uric acid levels tend to be higher because of decreasing urinary secretion or overproduction of uric acid. Among calcium channel blockers (CCBs) , long acting nifedipine and cilnidipine reveal serum uric acid lowering action. They decrease the production of uric acid precursor in skeletal muscles under anaerobic condition induced by hypertension or insulin resistance. Hyperuricemia is considered to be a risk factor of not only gout but also renal and cardiovascular diseases, thus, it is important to use CCBs without adverse effect on uric acid metabolisms.

Pendrin is a novel autoantigen recognized by patients with autoimmune thyroid diseases.

CONTEXT: Pendrin is an apical protein of thyroid follicular cells, responsible for the efflux of iodide into the follicular lumen via an iodide-chloride transport mechanism. It is unknown whether pendrin is recognized by autoantibodies. OBJECTIVE: Our objective was to examine the prevalence of pendrin antibodies in autoimmune thyroid diseases and compare with that of thyroglobulin, thyroperoxidase, TSH receptor, and sodium iodide symporter antibodies. DESIGN: In a prevalent case-control study, we analyzed the sera of 140 autoimmune thyroid disease cases (100 with Graves' disease and 40 with Hashimoto's thyroiditis) and 80 controls (50 healthy subjects, 10 patients with papillary thyroid cancer, 10 with systemic lupus erythematosus, and 10 with rheumatoid arthritis). Pendrin antibodies were measured by immunoblotting using extract of COS-7 cells transfected with pendrin and a rabbit polyclonal pendrin antibody. RESULTS: Pendrin antibodies were found in 81% of the cases and 9% of controls (odds ratio = 44; P < 0.0001). Among cases, pendrin antibodies were more frequent and of higher titers in Hashimoto's thyroiditis than in Graves' disease. Pendrin antibodies correlated significantly with thyroglobulin, thyroperoxidase, and sodium iodide symporter antibodies but not with TSH receptor antibodies. Pendrin antibodies were equally effective as thyroglobulin and thyroperoxidase antibodies in diagnosis of autoimmune thyroid diseases, especially Hashimoto's thyroiditis. CONCLUSIONS: The study identifies pendrin as a novel autoantigen recognized by patients with autoimmune thyroid diseases and proposes the use of pendrin antibodies as an accurate diagnostic tool.

A simple risk score to predict in-hospital death of elderly patients with acute decompensated heart failure--hypoalbuminemia as an additional prognostic factor.

BACKGROUND: Risk stratification for elderly patients with acute decompensated heart failure (ADHF) may help clinicians to select the appropriate therapy and raise the quality of care. METHODS AND RESULTS: The present study enrolled 349 patients aged over 65 years who were hospitalized with ADHF from January 2004 to October 2008. Five independent prognostic factors were identified by multivariate logistic regression analysis, and each factor was assigned a number of points proportional to its regression coefficient: prior heart failure hospitalization (2 points), sodium or=35 mg/dl (2 points), albumin or=980 pg/ml (2 points); in particular, hypoalbuminemia was identified as the strongest prognostic factor. The patients were stratified into 3 groups: low risk (0-4 points), moderate risk (5-7 points), and high risk (8-11 points). The respective in-hospital mortality rates were 1.6%, 15.8%, and 42.1% (P<0.05). CONCLUSIONS: In addition to known prognostic factors, hypoalbuminemia may provide important information for elderly patients with ADHF. A simple risk score may help to stratify the risk of in-hospital mortality and contribute to better clinical management of these elderly patients.

Exact location of the branching bundle in the living heart.

AIMS: The His bundle electrogram is believed to reflect the exact location of the His bundle. However, the distinction between distal His bundle potential and proximal right bundle branch potential is challenging. The aim of this study was to pinpoint the location of the branching point of the His bundle, and to compare that site with the site of recording of the largest His bundle electrogram (LH) during sinus rhythm. METHODS: We hypothesized that the site of earliest His activation (EH) during retrograde conduction via the left bundle branch is the branching point. We studied 15 nonconsecutive patients (mean age = 40 +/- 22 years; eight men). We performed a programmed stimulation from right ventricular apex until retrograde right bundle branch block appeared. At that point we measured (1) the distance between antegrade LH site and retrograde EH site and (2) the atrial-to-ventricular amplitude ratio (A/V ratio) at both sites. RESULTS: EH was recorded at the proximal electrode of the His bundle catheter in all patients. Mean distance between EH and LH was 9.8 +/- 2.5 mm. The mean A/V ratios at the EH site and the LH site were 1.01 +/- 0.42 and 0.08 +/- 0.06, respectively. DISCUSSION: This study showed that the EH site is located approximately 10-mm proximal to the LH site. The mean A/V ratio at the EH site during sinus rhythm is approximately 1.0. These observations suggest that the majority of His potentials reflect proximal right bundle activation. Before delivering radiofrequency energy in the para-Hisian area, attention should be paid to the presence of a His potential and to the A/V ratio, rather to the amplitude of the His electrogram.

Functional stabilization of Kv1.5 protein by Hsp70 in mammalian cell lines.

The aim of this study was to elucidate the mechanisms for regulations of cardiac Kv1.5 channel expression. We particularly focused on the role of heat shock proteins (Hsps). We tested the effects of Hsps on the stability of Kv1.5 channels using biochemical and electrophysiological techniques: co-expression of Kv1.5 and Hsp family proteins in mammalian cell lines, followed by Western blotting, immunoprecipitation, pulse-chase analysis, immunofluorescence and whole-cell patch clamp. Hsp70 and heat shock factor 1 increased the expression of Kv1.5 protein in HeLa and COS7 cells, whereas either Hsp40, 27 or 90 did not. Hsp70 prolonged the half-life of Kv1.5 protein. Hsp70 was co-immunoprecipitated and co-localized with Kv1.5-FLAG. Hsp70 significantly increased the immunoreactivity of Kv1.5 in the endoplasmic reticulum, Golgi apparatus and on the cell membrane. Hsp70 enhanced Kv1.5 current of transfected cells, which was abolished by pretreatment with brefeldin A or colchicine. Thus, Hsp70, but not other Hsps, stabilizes functional Kv1.5 protein.

Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients.

BACKGROUND: The angiotensin receptor blocker losartan inhibited urate transporter 1 (URAT1) according to in vitro experiments. However, it is still unknown whether the inhibitory effect of losartan on URAT1 contributes to its uricosuric action in humans. METHODS: Thirty-two patients with hypertension and nine patients with idiopathic renal hypouricemia (five with and four without hypertension) were enrolled for this study. Hypertensive patients were prescribed oral losartan (50 mg/day, n = 16) or candesartan (8 mg/day, n = 16). Before and after 1-month treatment, the serum concentration of urate (Sur) and creatinine (Scr), and the clearance value of urate (Cur) and creatinine (Ccr) were determined. Clearance studies using the URAT1 inhibitor benzbromarone (100 mg/day) or losartan (50 mg/day) loading test were also performed in these patients. RESULTS: Blood pressure (BP) significantly decreased in the patients treated with either losartan or candesartan. Losartan significantly reduced Sur, which was associated with a concomitant increase in the Cur/Ccr ratio, whereas candesartan did not alter these parameters. In hypertensive patients with loss-of-function mutation of URAT1, losartan did not alter either Sur or Cur/Ccr, nor did benzbromarone. The lack of effect of URAT1 inhibitors on renal excretion of urate was independent of the renal function of hypouricemic patients. On the other hand, both losartan and benzbromarone increased Cur/Ccr ratio in hypertensive patients harboring the wild URAT1 gene, regardless of the presence of hypouricemia. CONCLUSIONS: These findings suggested that losartan inhibited URAT1 and thereby it lowered Sur levels in hypertensive patients.

Long-term reliability of AAI mode pacing in patients with sinus node dysfunction and low Wenckebach block rate.

AIMS: To compare the risk of atrioventricular (AV) conduction disturbance between patients with sinus node dysfunction on AAI pacing who had a low or high Wenckebach block rate (WBR). METHODS AND RESULTS: Patients with sinus node dysfunction and normal AV conduction those underwent an electrophysiological study were studied. The patients were classified into two groups: Group L was with the patients with a WBR of 100 to 129 per minute and Group H was with the patients with a WBR > or = 130 per minute. All patients followed up every 3-6 months after an AAI pacemaker implantation. A total of 102 patients, including 35 Group L and 67 Group H, were followed for 90 +/- 44 months. Six patients died from non-cardiac cause and five patients required a new atrial lead implantation due to lead failure during follow-up. Symptomatic bradycardia requiring a new ventricular lead implantation developed in four patients (annual incidence 0.5%). In Group L, two patients developed AV block (annual incidence 0.7%). In Group H, two patients developed bradycardic atrial fibrillation (annual incidence 0.4%). Kaplan-Meier analysis revealed no significant difference between the two groups (P = 0.2983). CONCLUSION: These results suggest that a long-term risk of developing AV conduction disturbance is low even in patients with a WBR of 100 to 129 per minute.

[Idiopathic hyperuricemia with overproduction of uric acid].

Idiopathic hyperuricemia is generally defined as hyperuricemia caused by unknown origin. Idiopathic hyperuricemia is categorized as overproducing or underexcretion of uric acid. Overproduced uric acid is caused by increased biosynthesis of purine bodies, hypermetabolization of purine bodies, or increased intake of dietary purine bodies. Idiopathic hyperuricemia with overproducing uric acid can be diagnosed by amount of excreted uric acid in the urine. Recently it has been identified that hypertension are frequently associated with myogenic hyperuricemia converted from overproduced hypoxanthine in the skeletal muscles. Some anti-hypertensive drugs including alpha1 blocker, ACE inhibitor, alphabeta blocker, or long-acting Ca blocker attenuated the myogenic hyperuricemia. Thus, these drugs may be helpful in the management of hypertension with hyperuricemia.

[Other antihyperuricemic agents].

It has been reported that hyperuricemia might be responsible for cardiovascular diseases as well as gout and renal injury. Hypertension and hyperlipidemia, which are also responsible for cardiovascular diseases, are often associated with hyperuricemia. Thus, the treatment of hypertension and hyperlipidemia associated with hyperuricemia is also important. Losartan, an antihypertensive agent, and fenofibrate, an antihyperlipidemic agent, are known to have uric acid lowering effects. Both agents are useful for hyperuricemia with associated with hypertension and hyperlipidemia. In this section, we reported the characteristics and usefulness of these two agents in hyperuricemic patients with hypertension and hyperlipidemia.