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Biomedical subjects

Yuhei Kawano

Publications and source records attributed to Yuhei Kawano.

At least 73 records · Page 4Linked to original sources

The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics.

The response of blood pressure to thiazide diuretics (TZDs) differs among individuals. The prediction of the antihypertensive effect of TZDs is important for realizing individualized therapy in the management of hypertension. The aim of this study was to identify the single nucleotide polymorphisms (SNPs) susceptible to the antihypertensive effect of TZDs, particularly focusing on genes related to water-electrolyte absorption in the kidney. Seventy-six outpatients (mean age, 65.4+/-9.0 years) with essential hypertension (EHT) taking TZDs were retrospectively assessed. We defined as responders (R) those whose mean blood pressure was lowered by more than 5 mmHg after the use of TZDs. Forty-eight SNPs in 17 genes (ADD1, GNB3, TSC [SLC12A3], MLR [NR3C2], NCX1 [SLC8A1], WNK1, WNK4, AGT, ACE, AT1 [AGTR1], CYP11B2, ADRB1, ADRB2, ADRB3, ADRA1A, ADRA1B, ADRA2A) were genotyped in the 76 patients. The SNPs in TSC, MLR, NCX1, WNK1, and WNK4 were identified by direct sequencing and those with minor frequencies of greater than 5% were genotyped in this study. The comparison of polymorphism prevalence between R and non-responders (NR) showed significant differences in TSC C1784T (C allele vs. T allele, odds ratio (OR)=3.81, p =0.016, confidence interval (CI): 1.25-11.63) and ADRB3 T727C (Trp64Arg) (T allele vs. C allele, OR=4.59, p =0.005, CI: 1.54-13.68). The blood pressure (BP) in patients homozygous for the major alleles of both TSC C1784T and ADRB3 T727C were significantly reduced by TZD treatment; however, the BP in those homozygous for the minor allele and heterozygous (TSC C1784T: TT+CT; ADRB3 T727C: CC+CT) for both SNPs were not significantly changed after TZD treatment. Both newly detected TSC C1784T and ADRB3 T727C are gene polymorphisms susceptible to the antihypertensive effect of TZDs in patients with EHT. Thus, the prediction of BP reduction by TZDs may be possible by evaluating these two SNPs.

Benzothiadiazines↗

Diagnostic and prognostic value of plasma brain natriuretic peptide in non-dialysis-dependent CRF.

BACKGROUND: Brain natriuretic peptide (BNP) is useful for the evaluation of ventricular dysfunction in patients with various cardiac diseases. However, its diagnostic value has been considered to be limited in patients with chronic renal failure (CRF) because renal dysfunction itself may affect BNP levels. This study is designed to clarify the diagnostic and prognostic value of plasma BNP level in patients with CRF. METHODS: In 103 non-dialysis-dependent patients with CRF without heart failure and 60 hypertensive patients with normal renal function, echocardiographic examinations and BNP measurements were performed. RESULTS: Plasma BNP level was much greater in patients with CRF than in hypertensive controls; however, multiple regression analysis showed that left ventricular (LV) end-diastolic volume (EDV) index (LVEDVI) and the difference in mitral and pulmonary venous atrial wave duration (Ad-PVad), a marker of LV end-diastolic pressure, were independent determinants of plasma BNP levels in patients with CRF. The influence of LV overload (LVEDVI > or = 75 mL/m 2 and/or Ad-PVad < 0 milliseconds) on plasma BNP levels in subjects with CRF was independent of the severity of renal dysfunction. From Kaplan-Meier event-free curves (mean follow-up, 13 months), the incidence of heart failure was much greater in patients with a plasma BNP level of 150 pg/mL or greater ( P < 0.001). By means of multivariate Cox regression analysis, high plasma BNP level was the strongest predictor for heart failure events (hazard ratio, 6.31; P < 0.001). CONCLUSION: These findings support plasma BNP level as a reliable marker of LV overload, even in nondialysis patients with CRF. Also, a high BNP level (> or =150 pg/mL) may have powerful predictive potential for heart failure in these patients.

Aged↗

[Effects of nitrendipine on circadian variation of blood pressure in inpatients with renal parenchymal hypertension: assessment by ambulatory blood pressure monitoring].

OBJECTIVE: To study the effect of once-daily administration of a nitrendipine tablet 10 mg on 24-hour ambulatory blood pressure in inpatients with renal parenchymal hypertension. METHODS: Sixteen patients participated in the present study, and one patient was withdrawn because the baseline office blood pressure was less than 140/90 mmHg. In the baseline period, ambulatory blood pressure was monitored every 30 minutes for 30 hours. After the baseline measurement, nitrendipine 10 mg was orally administered once daily every morning for 7 days. The 30-hour ambulatory blood pressure monitoring was repeated after Day 6. RESULTS: Fifteen patients (aged 64.9 +/- 15.0 years) completed the study protocol. Baseline office blood pressure was 157.9 +/- 17.5/84.7 +/- 12.5 mmHg (mean +/- SD). Nitrendipine 10 mg tablets significantly reduced both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at least for 11 hours after administration compared with those at baseline. The rate of "Decrease" (reduction in blood pressure > or = 20/10 mmHg and/or achieved blood pressure < 140/90 mmHg at trough point) was 60.0% (9/15). Eleven patients were considered as effective cases at peak point (maximal reduction in blood pressure > or = 20/10 mmHg). The rate of "Decrease" in effective cases at peak point was 72.7% (8/11). CONCLUSION: These results suggest that a once-daily administration of nitrendipine 10 mg tablets is effective for the 24-hour control of blood pressure in patients with renal parenchymal hypertension.

Administration, Oral↗

Acetazolamide assisted Tc-99m MAG3 renography to assess renal blood flow reserve.

OBJECTIVE: The present study examines whether or not baseline and acetazolamide (ACZ) Tc-99m MAG3 renography can assess renal blood flow reserve. METHODS: Renography proceeded for 50 min after sequential injections of 370 MBq Tc-99m MAG3 for baseline renography and 10 min after a 1,000 mg injection of ACZ for ACZ renography. Effective renal plasma flow of renal cortex (cERPF) in each kidney and the percentage change in cERPF of those parameters (deltaERPF) were obtained before and after the administration of ACZ in 10 subjects without hypertension or diabetes (normal group), in 10 with essential hypertension (hypertensive group) and in 10 who had Type 2 diabetes with hypertension (diabetic group). A placebo test was performed in the 10 without hypertension or diabetes using distilled water instead of ACZ (placebo group). RESULTS: The placebo test performed in the 10 without hypertension or diabetes using distilled water instead of ACZ indicated that the parameter variance between the two types of renogram was below 3.2%. The cERPF of baseline and ACZ Tc-99m MAG3 renography and deltaERPF in the normal, hypertensive and diabetic groups were 89 +/- 10 and 110 +/- 10 ml/min, 89 +/- 14 and 117 +/- 22 ml/min, 100 +/- 23 and 112 +/- 23 ml/min, respectively, and 24.5 +/- 13.5%, 26.0 +/- 9.7% and 12.3 +/- 11.1%, respectively. The difference in the cERPF value was significant in the normal and hypertensive groups whereas this did not change in the diabetic group before or after ACZ administration. CONCLUSIONS: We suggested that the deltaERPF determined by baseline and ACZ Tc-99m MAG3 renography is a useful parameter for assessing renal blood flow reserve.

Acetazolamide↗

Efficacy of screening for primary aldosteronism by adrenocortical scintigraphy without discontinuing antihypertensive medication.

BACKGROUND: Recently, it has been proposed that discontinuation of antihypertensive medications is not necessarily essential for the measurement of plasma aldosterone-to-renin ratios. We examined the efficacy of adrenocortical scintigraphy performed without modification of antihypertensive medications. METHODS: A retrospective study was conducted on 119 patients, in whom functional tests, anatomic studies, and adrenocortical scintigraphy were replete. Interrelationship among these was studied. The patients tested were being treated with antihypertensive medications from several classes including angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers, diuretics, and spironolactone. RESULTS: Significantly higher percentage of scintigraphy positive patients had plasma aldosterone-to-renin ratio of greater than 25:1. Positive rate for adrenal nodules by anatomic studies was significantly higher in the scintigraphy positive patients than in the scintigraphy negative patients. Finally, the percentage of patients who underwent adrenalectomy was higher in the scintigraphy positive patients than in the scintigraphy negative patients. CONCLUSIONS: We conclude that adrenocortical scintigraphy is a valid evaluation tool for primary aldosteronism and that the discontinuation of antihypertensive medications is not a requirement for this test.

Adult↗

Influence of low high-density lipoprotein cholesterol on left ventricular hypertrophy and diastolic function in essential hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy and LV diastolic dysfunction, which are common cardiac changes in hypertensive patients, are modified by several nonhemodynamic (eg, genetic, neurohumoral, and metabolic) factors. However, the influence of serum lipids on these LV changes has not been sufficiently studied. Although low high-density lipoprotein (HDL) cholesterol is well known to be a major risk factor for coronary heart disease, it is unclear whether HDL cholesterol plays a role in hypertensive heart disease. METHODS: In 274 patients with treated essential hypertension, two-dimensional and Doppler echocardiography were performed, and LV mass, ratio of peak velocity of atrial filling to early diastolic filling (A to E ratio [A/E]), and deceleration time of the E-wave were evaluated. The relationship of dyslipidemia, especially low HDL cholesterol, to LV hypertrophy and diastolic function was investigated in these patients. RESULTS: In a univariate regression analysis, HDL cholesterol was inversely associated with LV mass, A/E, and deceleration time. The association of HDL cholesterol with LV diastolic function was observed in both men and women. Its association with LV mass was gender-dependent, being significant only in women. Triglycerides were weakly correlated with LV mass and A/E, but total and low-density lipoprotein cholesterol had no correlations with these indices. In a multiple regression analysis, only low HDL cholesterol among several lipid levels was an independent predictor of both LV mass and LV diastolic dysfunction. CONCLUSIONS: Our findings suggest that low HDL cholesterol may unfavorably modify LV structure and diastolic function in patients with treated essential hypertension.

Aged↗

Endothelin a receptor blockade and endothelin B receptor blockade improve hypokalemic nephropathy by different mechanisms.

Hypokalemia causes renal tubulointerstitial injury with an elevation in renal endothelin-1 (ET-1). It was hypothesized that hypokalemic tubulointerstitial injury is ameliorated by the blockade of ET-A receptors (ETA), whereas ET-B receptor (ETB) antagonism may exacerbate the injury, because ETB is thought to mediate vasodilation. Rats were fed a K(+)-deficient diet alone (LC) or with an ETA-selective antagonist ABT-627 (LA) or an ETB-selective antagonist A-192621 (LB) for 8 wk. Control rats were on a normal K(+) diet alone or with the ETA-selective or ETB-selective antagonists. The severity of hypokalemia was not significantly different among LA, LB, and LC. LC developed tubulointerstitial injury with an elevation of renal preproET-1 mRNA level. There was an increase in tubular osteopontin expression, macrophage infiltration, collagen accumulation, and tubular cell hyperplasia. ETA blockade significantly ameliorated all parameters for renal injury in the cortex without suppressing local ET-1 and ETA expression. By contrast, ETB blockade significantly reduced local ET-1 and ETA expression and improved the injury to a similar extent in the cortex. In the medulla, ETA or ETB blockade only partially blocked renal injury. ETA blockade did not affect BP in normokalemic or hypokalemic rats. ETB blockade induced a BP elevation with a decrease in urinary Na(+) excretion in normokalemic but not in hypokalemic rats. These results indicate that ET-1 can mediate hypokalemic renal injury in two different ways: by directly stimulating ETA and by locally promoting endogenous ET-1 production via ETB. Thus, ETA as well as ETB blockade may be renoprotective in hypokalemic nephropathy.

Albuminuria↗

Gene expression, secretion, and autocrine action of C-type natriuretic peptide in cultured adult rat cardiac fibroblasts.

C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is known to be synthesized in the central nervous system and vascular endothelial cells, in contrast to atrial natriuretic peptide and brain natriuretic peptide. However, there have been no studies concerning CNP production in cultured cardiac cells. Here, we examined the production and the local effect of CNP in cultured ventricular cells. Under serum-free conditions, adult rat cardiac fibroblasts secreted immunoreactive CNP time dependently. TGF-beta1, basic fibroblast growth factor, and endothelin-1 significantly stimulated CNP secretion. Northern blot analysis detected significant expressions of CNP and its specific receptor (guanylyl cyclase-B) mRNA in cardiac fibroblasts. CNP stimulated intracellular cGMP production in fibroblasts more intensely than atrial and brain natriuretic peptides. CNP inhibited both DNA and collagen syntheses of cardiac fibroblasts, and these inhibitory effects by CNP were stronger than by atrial and brain natriuretic peptides. The inhibition by CNP of DNA and collagen syntheses was reproduced by a cGMP analog, 8-bromo cGMP. The present findings demonstrate that CNP is synthesized in and secreted from cardiac fibroblasts and suggest that CNP has a suppressive effect on fibroblast proliferation and extracellular matrix production, probably via the guanylyl cyclase-B-mediated cGMP-dependent process. CNP produced by cardiac fibroblasts may play a role as an autocrine regulator against excessive cardiac fibrosis.

Age Factors↗

An alternative fast and convenient genotyping method for the screening of angiotensin converting enzyme gene polymorphisms.

Insertion/deletion (I/D) polymorphisms in intron 16 of the angiotensin converting enzyme gene (ACE) are associated with the plasma angiotensin converting enzyme (ACE) levels, and individuals with the DD allele have been reported to be more susceptible to cardiovascular disease than those without. The conventional genotyping method for the screening of I/D polymorphisms, which involves polymerase chain reaction (PCR)-gel electrophoresis, is laborious and time-consuming. In this study, we assessed the use of TaqMan-PCR genotyping for the screening of I/D polymorphisms as a replacement for the conventional method. We genotyped seven single nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with the I/D polymorphisms, and calculated the LD coefficients of the I/D polymorphisms. We found that three polymorphisms, rs4331, rs4334 and rs4341, exhibited the highest LD coefficients (D' = 1.000; r2 = 0.967) and that the genotyping of rs4341 by the TaqMan-PCR method yielded the best discrimination among the different genotypes. Genotyping of 511 samples took only 2 h and the amount of DNA required for each test was only 6 ng by the TaqMan-PCR method using rs4341. In the course of this study, we identified a novel additional polymorphism (a deletion of six amino acids) in exon 13, near rs4316. The deletion allele encoded the testicular ACE, but not the plasma ACE. We concluded that genotyping of the rs4341 ACE polymorphism by the TaqMan-PCR method is a fast and convenient alternative method for direct I/D genotyping. We also concluded that testicular ACE may manifest a deletion of six amino acids that may result in deleterious function of this enzyme.

Adult↗

Microalbuminuria and cardiovascular events in elderly hypertensive patients without previous cardiovascular complications.

To assist in the development of better treatments for elderly hypertensive patients, we studied the degree to which the baseline values of urinary albumin excretion (UAE) and other cardiovascular risk factors were predictive of cardiovascular complications in a cohort of elderly hypertensive patients. In 1994, we adopted 144 elderly hypertensive patients, who had been treated for more than 6 years at various clinics and more than 1 year at the National Cardiovascular Center, Osaka, Japan. They were divided into 2 groups: a NA group (n=111) with normoalbuminuria (UAE<30mg/day) and an MA group (n=33) with microalbuminuria (UAE 30-300 mg/day). At baseline, the two groups were similar with respect to systolic and diastolic blood pressure (SBP/DBP), pulse pressure (PP), age, ratio of males to females, serum creatinine, uric acid, total cholesterol, fasting plasma glucose (FPG), and creatinine clearance (CCr). PP was calculated as SBP minus DBP. The efficacy of blood pressure (BP) control was similar in both groups during the 8-year follow up period; however, a total of 14 cardiovascular events occurred in the MA (6/33) and NA (8/111) groups, with the MA group showing the higher incidence rate by multiple logistic regression analysis (p<0.05). At 8 years of follow-up, PP and age were correlated with UAE (p<0.05, p<0.001). At the same time point, CCr was correlated with UAE at baseline (p<0.05). The results indicated that, in elderly hypertensive patients without previous cardiovascular complications, microalbuminuria can be a predictor of cardiovascular events irrespective of conventional BP control.

Aged↗

Japanese society of hypertension (JSH) guidelines for self-monitoring of blood pressure at home.

UNLABELLED: Home blood pressure (BP) measurements are indispensable for the improvement of hypertension management in medical practice as well as for the recognition of hypertension in the population. The Working Group for Establishment of Guidelines for Measurement Procedures of Self-Monitoring of Blood Pressure at Home of the Japanese Society of Hypertension has established standards for all techniques and procedures of home BP measurements. The recommendations are as follows. RECOMMENDATION: 1) Arm-cuff devices based on the cuff-oscillometric method that have been validated officially, and the accuracy of which has been confirmed in each individual, should be used for home BP measurement. 2) The BP should be measured at the upper arm. Finger-cuff devices and wrist-cuff devices should not be used for home BP measurements. 3) Devices for home BP measurement should be adapted to the American Association for Medical Instrumentation (AAMI) standards and the British Hypertension Society (BHS) guidelines. In addition, the difference between the BP measured by the auscultatory method and that measured using the device should be within 5 mmHg in each individual. The home measurement device should be validated before use, and at regular intervals during use. 4) Home BP should be monitored under the following conditions. The morning measurement should be made within 1 h after waking, after micturition, sitting after 1 to 2 min of rest, before drug ingestion, and before breakfast. The evening measurement should be made just before going to bed, sitting after 1 to 2 min of rest. 5) Home BP should be measured at least once in the morning and once in the evening. 6) All home BP measurements should be documented without selection, together with the date, time, and pulse rate. Use of devices with a printer or an integrated circuit memory is useful to avoid selection bias. 7) The home BP in the morning and that in the evening should be averaged separately for a certain period. The first measurement on each occasion should be used for totaling. 8) Home BP values averaged for a certain period indicate hypertension when 135/80 mmHg and over and definite hypertension when 135/85 mmHg and over. Normotension is defined as less than 125/80 mmHg and definite normotension as less than 125/75 mmHg. Home BP measurements based on these guidelines can be considered an appropriate tool for clinical decision-making, and it is hoped that these guidelines will serve to reduce confusion and confirm the place of home BP measurement in clinical practice.

Blood Pressure↗

Carotid intima-media thickness is correlated with impairment of coronary flow reserve in hypertensive patients without coronary artery disease.

Hypertensive individuals occasionally experience angina-like chest pain despite having angiographically normal coronary arteries, and the etiology of this phenomenon has been suggested to be associated with depressed coronary flow reserve (CFR). Carotid intima-media thickness (IMT) assessed by ultrasound is correlated with not only cerebrovascular disease but also coronary artery disease and left ventricular hypertrophy (LVH). The aim of our study was to investigate the association between CFR and carotid IMT in patients with essential hypertension. We performed transthoracic Doppler recording of diastolic coronary flow velocity in the left anterior descending coronary artery at baseline and after maximal vasodilation by adenosine triphosphate infusion in 24 normotensive subjects and 125 hypertensive patients. CFR was defined as the ratio of hyperemic to basal averaged peak coronary flow velocity. Common cardiovascular risk factors, left ventricular mass index (LVMI), relative wall thickness (RWT), and carotid IMT were evaluated. The CFR of hypertensive patients (2.55 +/- 0.52) was significantly decreased compared with that of normotensive subjects (3.15 +/- 0.45). CFR showed a significant correlation with age, systolic blood pressure, RWT, and carotid IMT. Stepwise regression analysis revealed that, among carotid IMT, LVMI and RWT, only carotid IMT was a strong and independent parameter for predicting CFR in hypertensive patients. In conclusion, B-mode ultrasound scanning of the carotid artery seemed to be of clinical value in the screening of patients with LVH and impaired microcoronary circulation. These associations may explain the links between cardiac and cerebrovascular involvements in patients with hypertension.

Aged↗

Association between left ventricular diastolic dysfunction and renal hemodynamic change in patients with treated essential hypertension.

The heart and kidneys are important target organs in hypertension. Early signs of hypertensive target organ damage can be detected by evaluating left ventricular (LV) diastolic function and intrarenal hemodynamics using Doppler ultrasonography. However, it has not been sufficiently clarified whether cardiac damage and renal impairment progress in parallel, especially from the early stage. In the present study, Doppler echocardiography and renal Doppler ultrasonography were performed in 99 patients with treated essential hypertension, and LV diastolic filling parameters, ie., the velocity ratio of atrial filling to early diastolic filling (A/E), and the deceleration time of the E wave (DcT) and renal Doppler parameters, i.e., the diastolic to systolic ratio (D/S) and resistance index (RI), were determined. D/S was negatively correlated and RI was positively correlated with A/E and DcT. These cardiac and renal Doppler parameters were also associated with age, diastolic blood pressure, creatinine clearance, and/or glucose levels. By multiple regression analysis, D/S was found to have a significant association with DcT, independent of other clinical parameters, including age. In subgroup analysis in which patients were divided by their glucose tolerance, a significant correlation between renal Doppler parameters and LV diastolic function was observed in subjects with normal glucose tolerance, but this correlation disappeared in those with impaired glucose tolerance and diabetes mellitus. The present findings show that there is a significant relation between LV diastolic function and renal Doppler parameters in treated hypertensive patients, and suggest that cardiac damage progresses in parallel with renal involvement in these patients from the early stage.

Aged↗

Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity.

von Willebrand factor (VWF) is synthesized primarily in vascular endothelial cells and secreted into the plasma as unusually large VWF multimers. Normally, these multimers are quickly degraded into smaller forms by a plasma metalloproteinase, VWF-cleaving protease (VWF-CP). Decreases in the activity of this enzyme result in congenital and acquired thrombotic thrombocytopenic purpura (TTP). The human VWF-CP has recently been purified. Cloning of the corresponding cDNA revealed that the 1,427-aa polypeptide is a member of the ADAMTS gene family, termed ADAMTS13. Twelve rare mutations in this gene have been identified in patients with congenital TTP. Here, we report missense and nonsense mutations in two Japanese families with Upshaw-Schulman syndrome, congenital TTP with neonatal onset and frequent relapses. The comparison of individual ADAMTS13 genotypes and plasma VWF-CP activities indicated that the R268P, Q449stop, and C508Y mutations abrogated activity of the enzyme, whereas the P475S mutant retained low but significant activity. The effects of these mutations were further confirmed by expression analysis in HeLa cells. Recombinant VWF-CP containing either the R268P or C508Y mutations was not secreted from cells. In contrast, Q449stop and P475S mutants were normally secreted but demonstrated minimal activity. Genotype analysis of 364 Japanese subjects revealed that P475S is heterozygous in 9.6% of individuals, suggesting that approximately 10% of the Japanese population possesses reduced VWF-CP activity. We report on a single-nucleotide polymorphism associated with alterations in VWF-CP activity; it will be important to assess this single-nucleotide polymorphism as a risk factor for thrombotic disorders.

ADAM Proteins↗

Plasma atrial natriuretic peptide concentration inversely correlates with left atrial collagen volume fraction in patients with atrial fibrillation: plasma ANP as a possible biochemical marker to predict the outcome of the maze procedure.

OBJECTIVES: We hypothesized that the plasma atrial natriuretic peptide (ANP) level reflects atrial degenerative change and may predict the outcome of the maze procedure. BACKGROUND: Although a larger preoperative left atrial dimension and longer duration of atrial fibrillation (AF) have been reported in patients with persistent AF than in those with sinus rhythm (SR), these individual factors were not enough to predict the outcome of the maze procedure. METHODS: Preoperative plasma ANP levels were measured in consecutive 62 patients who underwent the Kosakai's modified maze procedure. Moreover, we performed histological and molecular biological examinations in the resected left atrial tissues. RESULTS: The preoperative plasma ANP was lower in the AF group (n = 13) than it was in the SR group (n = 49) (p < 0.001). Multiple logistic regression analysis revealed that duration of AF and plasma ANP were independently associated with postoperative cardiac rhythm. Among 41 patients with a higher plasma ANP or shorter duration of AF than the median value, SR was restored in 95% of patients. In contrast, in 21 patients with a lower plasma ANP and a longer duration of AF than the median value, SR was restored only in 48% of patients. Histological examination revealed that the collagen volume in the left atrial tissue was higher in AF than it was in SR and inversely correlated with plasma ANP. In addition, the messenger RNA expressions of ANP, collagen type I and type III were lower in AF than they were in SR. CONCLUSIONS: These results suggest that a combination of plasma ANP and/or duration of AF may predict the success rate for the maze operation. Advanced atrial degenerative change may result in a decrease of atrial ANP secretion.

Aged↗

Verification of 525 coding SNPs in 179 hypertension candidate genes in the Japanese population: identification of 159 SNPs in 93 genes.

Single-nucleotide polymorphisms (SNPs) located in coding regions (coding SNPs; cSNPs) with amino acid substitution can potentially alter protein function. Therefore, identification of the nonsynonymous cSNPs of the genes of common diseases is valuable in tests of association with phenotypes. In this study, we validated 525 candidate cSNPs from 179 hypertension candidate genes deposited in the publicly available database dbSNP by DNA sequencing of samples from 32 Japanese individuals. We identified a total of 143 SNPs (27%) in 93 hypertension candidate genes. We also identified 16 new SNPs, for a total of 159 SNPs. Of the 159 SNPs thus identified, 104 were nonsynonymous. We estimate that approximately 20% of the SNPs deposited in dbSNP database showed a minor allele frequency of over 5%. The candidate SNPs for hypertension identified in this study would be valuable for association studies with hypertension to accelerate the identification of hypertension genes.

Gene Frequency↗

Decreases in serum uric acid by amelioration of insulin resistance in overweight hypertensive patients: effect of a low-energy diet and an insulin-sensitizing agent.

BACKGROUND: Hyperuricemia and hyperinsulinemia/insulin resistance are commonly seen in obese subjects and hypertensive patients. To clarify whether the insulin resistance plays a role in hyperuricemia, we investigated alterations in serum uric acid (UA) concentrations during treatment with a low-energy diet or an insulin-sensitizing agent in overweight hypertensive patients. METHODS: Twenty-eight overweight hypertensive patients (14 men and 14 women, mean age 61 +/- 2 years) were assigned to a weight reduction program with a low-energy diet (3360 kJ/day for 3 weeks, n = 14) and to treatment with troglitazone (200 mg twice daily for 8 weeks, n = 14). Measurements of body weight, blood pressure (BP), serum UA, and a 75-g oral glucose tolerance test were performed at baseline and the end of the intervention periods. RESULTS: Body weight and BP decreased significantly in the diet group but not in the troglitazone group at the end of the intervention periods. Levels of blood glucose, plasma insulin, and homeostasis model assessment-insulin resistance index (HOMA-R) improved similarly in the two groups. Serum UA concentration decreased by treatment both in the diet (0.4 +/- 0.2 mg/dL, P < .05) and troglitazone groups (1.0 +/- 0.2 mg/dL, P < .001). CONCLUSIONS: The amelioration of insulin resistance by either a low-energy diet or troglitazone decreased the serum UA level in overweight hypertensive patients. Insulin resistance or hyperinsulinemia, independent of body weight and BP, may play an important role in UA metabolism in multiple risk factor syndrome.

Adult↗