Achievement rate of target blood pressure in patients with hypertension treated by hypertension specialists and non-specialists in a real-world setting.

Hypertension remains a major global healthcare issue. Considering that most Japanese patients with hypertension are managed by general practitioners, hypertension specialists should be involved in actual clinical practice. We investigated the blood pressure (BP), guidelines recommended for achievement rate of the target BP, and clinical variables of patients with hypertension treated by hypertension specialists and those treated by non-specialists in a real-world setting. Factors associated with the target BP achievement in this population were also investigated. Outpatients with hypertension from 12 medical facilities in Okinawa Prefecture were enrolled (n = 1469 [specialist group, 794; non-specialist group, 675]; mean age, 64.2 years; females, 45.8%). For all patients, BP and rate of the target BP achievement were 129.0 ± 15.5/74.6 ± 10.6 mmHg, and 51.8%, respectively. BP and the rate of target of BP achievement were 128.0 ± 15.1/73.4 ± 10.4 mmHg and 56.7% in the specialist group, and they were 130.1 ± 15.9/76.0 ± 10.8 mmHg and 46.1% in the non-specialist group. The urinary salt excretion and obesity rates were comparable between the specialist and non-specialist groups. Multivariable logistic analyses indicated that hypertension specialists and good medication adherence were positive factors, whereas obesity, chronic kidney disease, diabetes mellitus, and urinary salt excretion were inverse factors associated with target BP achievement in this population. Initiatives for salt reduction, medication adherence, and proper obesity management are crucial to improving BP management in patients with hypertension. Hypertension specialists are expected to play an essential role in them. For all patients, the target blood pressure (BP) achievement rate were 51.8%. Hypertension specialists and good medication adherence were positive factors in achieving target BP; conversely, obesity, diabetes mellitus, chronic kidney disease, and high urinary salt excretion were inverse factors in achieving target BP among patients with hypertension.

Strategies for improving the treatment and control of hypertension in Japan.

Despite the significant advancements in the diagnosis and treatment of hypertension, the burden of hypertension remains a major global health care concern. In Japan, estimates show that more than two-thirds of the population have uncontrolled hypertension, regardless of whether they were taking antihypertensive medication. To improve hypertension management, hypertension guidelines have been developed and updated regularly by hypertension societies across various countries and regions. The Japanese Society of Hypertension (JSH) updated the Guidelines for the Management of Hypertension in 2019 (JSH 2019). The JSH 2019 aims to establish a standard management strategy for hypertension and provide evidence to all health care providers. One of its updated main features is its proposal for multidisciplinary team-based care (TBC) involving physicians, pharmacists, nurses, dietitians, and other health care providers. The TBC will help initiate and intensify the management of hypertension, as well as combat clinical inertia, which is expected to contribute to uncontrolled blood pressure and subsequent development of cardiovascular diseases. This is consistent with the recommendations from recent major guidelines on hypertension management. Moreover, to reduce the evidence-practice gap in hypertension management, it is essential to disseminate the essence of the guidelines and provide hypertension education programs for all health care providers and patients. This review summarizes the points of the JSH 2019-based strategy for improving hypertension management and discusses guidelines for its implementation into actual clinical practice.

Salt and potassium intake evaluated with spot urine and brief questionnaires in combination with blood pressure control status in hypertensive outpatients in a real-world setting.

Reducing salt and increasing potassium intake are recommended lifestyle modifications for patients with hypertension. The estimated 24-h urinary salt excretion value from spot urine using Tanaka's formula and the salt check-sheet scores, questionnaire-based scores of salt intake, are practical indices of daily salt intake. However, few studies have evaluated salt intake with these methods in hypertensive outpatients. We examined salt and potassium intake with the spot urine method and the salt check-sheet scores of hypertensive outpatients in a multi-facility, real-world setting and examined whether the salt or potassium intake evaluated with these methods related to inadequate blood pressure control. Hypertensive outpatients from 12 medical facilities in the Okinawa prefecture were enrolled from November 2011 to April 2014 (n = 1559, mean age 63.9 years, 46% women). The mean blood pressure, urinary salt excretion value, urinary potassium excretion value, and total score on the salt check-sheet were 129/75 mmHg, 8.7 g/day, 1.6 g/day, and 10.4 points, respectively. The urinary salt excretion value and total score on the salt check-sheet but not urinary potassium excretion value were associated with inadequate blood pressure control (≥140/90 mmHg). Higher body mass index, estimated glomerular filtration rate, urinary potassium excretion value, total score on the salt check-sheet, and presence of inadequate blood pressure control were associated with high urinary salt excretion (≥10.2 g/day). In conclusion, hypertensive outpatients with high urinary salt excretion values estimated using Tanaka's formula or with high scores on the salt check sheet may be candidates for more intensive salt reduction guidance.

Effect of Mineralocorticoid Receptor Blockade on Arterial Stiffness and Endothelial Function: A Meta-Analysis of Randomized Trials.

Although numerous studies have confirmed the beneficial effects of pharmacological therapy for arterial stiffness and endothelial dysfunction, which are predictors/therapeutic targets for cardiovascular diseases, only a few overall quantitative evaluations of MRAs (mineralocorticoid receptor antagonists) exist. We searched PubMed and Cochrane CENTRAL (Cochrane Central Register of Controlled Trials) for randomized trials evaluating MRA effects on arterial stiffness measured by pulse wave velocity (PWV) or augmentation index and endothelial function measured by flow-mediated dilation. Data from the included trials were pooled by using random-effects meta-analysis of the weighted mean difference (MD) between the comparator groups. The primary outcome was the MD of PWV. In 11 trials including 515 patients, the MRA treatment reduced the PWV when compared with control (MD, -0.75 m/s [95% CI, -1.12 to -0.39], P<0.00001), without heterogeneity. There were comparable effects of MRA on carotid-femoral PWV and those on other forms of PWV (P=0.705 for heterogeneity). The effects of MRA on PWV were independent of blood pressure reduction related to the treatment according to meta-regression analysis. The MRA treatment reduced the augmentation index compared with control in 5 trials including 283 patients (MD, -6.74% [95% CI, -10.26 to -3.21], P=0.0002) and increased the flow-mediated dilation in 11 trials including 570 patients (MD, 1.18% [95% CI, 0.14 to 2.23], P=0.03). In conclusion, the current meta-analysis demonstrates the beneficial effects of MRA on PWV, augmentation index, and flow-mediated dilation.

Cardiac auscultation skills among junior doctors: effects of sound simulation lesson.

OBJECTIVES: To evaluate the effect of a sound simulation lesson to improve cardiac auscultation skills among junior doctors. METHODS: This study is based on the design of test comparison before and after educational intervention using a convenient sample. For 50 junior doctors in Japan, diagnostic accuracy before and after a sound simulation lesson for cardiac auscultation skills was compared. There were 15 doctors who experienced cardiology rotation. The lesson used seven abnormal cardiac recordings (third heart sound, double gallop, aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, and pericardial friction rub). At tests before and after the lesson, the doctors listened to random sound outputs of the same seven recordings, chose diagnostic findings from multiple-choice items, and obtained individual diagnostic accuracy based on the total number of choosing correct findings. Top 10 doctors obtaining the greatest individual accuracy received a commendation. RESULTS: Pre-lesson diagnostic accuracy was not different between doctors with cardiology rotation training (total diagnostic accuracy of the group, 27/105 [26%]) and those without cardiology rotation (70/245 [29%]). Compared to pre-lesson, post-lesson total diagnostic accuracy significantly improved with about two-folds (97/350 [28%] vs 170/350 [61%]; McNemar Test, p<0.0001). The improvement was significant for double gallop (5/50 [10%] vs. 15/50 [30%]), mitral stenosis (0/50 [0%] vs. 6/50 [12%]), and pericardial friction rub (1/50 [2%] vs. 35/50 [70%]). CONCLUSIONS: The use of a simple sound simulation lesson may help junior doctors to learn cardiac auscultation skills. Clinician educators are encouraged to use this strategy in addition to cardiology rotation training.

Factors Associated with Outcomes of Percutaneous Transluminal Renal Angioplasty in Patients with Renal Artery Stenosis: A Retrospective Analysis of 50 Consecutive Cases.

BACKGROUND: The results of recent trials have brought some confusion to the treatment strategy for renal artery stenosis (RAS). To evaluate the applicability of percutaneous transluminal renal angioplasty (PTRA) for RAS, we extracted the factors that may affect the effectiveness of PTRA from cases experienced at a hypertension center. METHODS AND RESULTS: We retrospectively assessed the blood pressure (BP) lowering effects and renoprotective effects in 50 consecutive patients that had hemodynamically significant RAS and had undergone PTRA and stenting during 2001-2005. Subjects were diagnosed with atherosclerotic RAS (42), fibromuscular dysplasia (6), or Takayasu disease (2). After PTRA, BP significantly lowered from 152.3/80.3 mmHg to 132.6/73.2 mmHg (p < 0.05), but the estimated glomerular filtration rate (eGFR) did not change significantly. There were no factors associated with the BP lowering effects of PTRA. The baseline resistive index (RI) was negatively correlated with the change in eGFR (p < 0.05). After correction for age, sex, BMI, and the dose of contrast medium, the association of RI with change in eGFR remained significant. CONCLUSION: In cases with hemodynamically significant RAS, PTRA lowered BP but was not effective in improving renal function. Higher baseline RI may be a factor for predicting poor clinical course of renal function after PTRA.

Control of home blood pressure with an amlodipine- or losartan-based regimen and progression of carotid artery intima-media thickness in hypertensive patients: the HOSP substudy.

Carotid artery intima-media thickness (IMT) has emerged as a predictor of cardiovascular events. Home blood pressure (BP) is more closely associated with cardiovascular prognosis than clinic BP. The aim of this study was to compare the progression of carotid IMT with respect to strict and mild control of morning home systolic BP (SBP) and amlodipine- and losartan-based antihypertensive therapy in hypertensive patients. Subjects included 80 hypertensive outpatients who participated in the Hypertension Control Based on Home Systolic Pressure (HOSP) pilot study. After a 1-month drug-free period, the patients were randomly assigned to either the strict control group (target SBP <130 mm Hg) or the mild control group (130-139 mm Hg) and to either the amlodipine group or the losartan group. Additional antihypertensive drugs were added if target BP was not achieved with monotherapy. Morning SBP achieved target levels during 5 years in the strict control group and in the mild control group, while it was comparable between amlodipine and losartan groups. In all patients, mean and maximum carotid IMT increased significantly. Changes in carotid IMT did not differ between strict and mild control groups. Changes in mean carotid IMT in amlodipine group were smaller than those in losartan group at year 1, but were not different between the two groups at year 5. In conclusion, carotid IMT increased over time in hypertensive patients in spite of the strict control of home BP. Amlodipine may slow the progression of IMT more than losartan, although a difference was not obvious after 5 years.

[Current strategy for management of resistant hypertension].

Inadequate control of blood pressure during antihypertensive treatment remains a major problem in preventive cardiovascular and renal disease. Major causes of resistant hypertension are following: problems in measuring technique, presence of white coat effect, poor adherence of patient, obesity, excessive alcohol intake, sleeping apnea syndrome, excess of body fluid, inappropriate use of hypertensive or anti-antihypertensive drug/supplement, especially their combination, and presence of secondary hypertension. Practitioners have to seek for the causes around their patients' lifestyle, prescription, secondary hypertension, after ruling out pseudo-hypertension or white coat hypertension. Evaluation of complications is also important in management of resistant cases, because of their high prevalence of target organ damage.

Association of intima-media thickening of carotid artery with genetic polymorphisms of the regulator of G-protein signaling 2 gene in patients with hypertension and in the general population.

Regulator of G-protein signaling 2 (RGS2) is a key molecule in signal pathways of vasoactive peptides, such as angiotensin II and endothelin 1, and is believed to have an important role in the pathophysiology of atherosclerosis. We have previously reported that common polymorphisms of RGS2 are associated with hypertension in Japanese. In this study, we studied whether the three previously identified common polymorphisms of RGS2 (-638A>G, 1026T>A and 1891-1892delTC) could be implicated in carotid atherosclerosis in Japanese patients with hypertension (459 men and 382 woman) and in a Japanese general population (814 men and 956 woman). We assessed two criteria for carotid atherosclerosis: maximal intima-media thickness (M-IMT) and mean-IMT. When subjects with atherosclerotic lesions were defined as having mean-IMT≥1.0 mm, multivariate logistic regression analysis performed after adjusting for confounding factors showed a significant association of the three common polymorphisms, -638A>G (AA versus AG+GG: odds ratio (OR), 1.55; 95% confidence interval (CI), 1.105-2.185; P=0.0113 only for the general population), 1026T>A (TT versus TA+AA: OR, 1.42; 95% CI, 1.027-1.972; P=0.034 for hypertensive subjects and OR, 1.56; 95% CI, 1.129-2.151; P=0.0071 for the general population), and 1891-1892delTC (II versus ID+DD: OR, 1.44; 95% CI, 1.043-2.008; P=0.028 for hypertensive subjects, OR, 1.32; 95% CI 1.002-1.742; P=0.048 for the total general population and OR 1.59; 95% CI 1.155-2.207; P=0.0047 for the general population), with carotid atherosclerosis. When atherosclerosis was defined as M-IMT 1.0 mm, the values of M-IMT were also significantly different between the three genotypes in the three common polymorphisms. Taken together, these data suggest that genetic polymorphisms in RGS2 are associated with intima-media thickening of carotid artery in humans.

Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers.

BACKGROUND: The response of blood pressure (BP) to L-type dihydropyridine calcium-channel blockers (dCCBs) differs among individuals. METHODS AND RESULTS: A pharmacogenomic analysis was undertaken in 161 patients with essential hypertension who were treated with dCCBs to study whether genetic polymorphisms of the calcium channel alpha1C and alpha1D subunit genes, CACNA1C and CACNA1D, are associated with the antihypertensive effects of dCCBs. Responders were defined as those in whom systolic BP (SBP) was lowered by more than 20 mmHg or diastolic BP (DBP) was lowered by more than 10 mmHg after treatment with dCCBs. Eleven sequence-proven polymorphisms of CACNA1C and 5 common polymorphisms of CACNA1D chosen from a public database were subjected to genotypic analysis. The comparison of polymorphism prevalence between responders and nonresponders showed significant differences in CACNA1D rs312481G>A and rs3774426C>T, and in CACNA1C 527974G>A. There were significant differences in SBP or DBP between alleles in these single nucleotide polymorphisms (SNPs). A much more significant reduction in BP was observed for the combined presence of these SNPs. CONCLUSIONS: Three SNPs in CACNA1D or CACNA1C are genetic polymorphisms conferring sensitivity to the antihypertensive effects of L-type dCCBs in patients with hypertension. The BP reduction by L-type dCCBs might be predicted by evaluating these polymorphisms.

Associations of hypertension and its complications with variations in the xanthine dehydrogenase gene.

Hyperuricemia and oxidative stress participate in the pathophysiology of hypertension and its complications. Xanthine dehydrogenase (XDH) produces urate and, in its oxidase isoform, reactive oxygen species. Here we have studied whether or not the genetic variations in XDH could be implicated in hypertension and its complications. By sequencing the promoter region and all exons of XDH in 48 subjects, we identified three missense mutations (G172R, A932T, N1109T) in a heterozygous state in addition to 34 variations, including 15 common single nucleotide polymorphisms (SNPs). The three missense mutations and eight common SNPs (11488C>G, 37387A>G, 44408A>G, 46774G>A, 47686C>T, 49245A>T, 66292C>G, and 69901A>C) were genotyped in 953 hypertensive Japanese subjects and in 1,818 subjects from a general Japanese population. Four hypertensive patients with rare missense mutations (G172R or N1109T) in homozygous form had severe hypertension. Multivariate logistic regression analysis showed a significant association of three SNPs with hypertension in men: 47686C>T (exon 22, odds ratio [OR]: 1.52, p = 0.047) and 69901A>C (intron 31, OR: 3.14, p = 0.039) in the recessive model, and 67873A>C (N1109T) (exon 31, OR: 1.84, p = 0.018) in the dominant model. After full adjustment for all confounding factors, only one polymorphism (69901A>C) was found to be associated with carotid atherosclerosis in the dominant model (p = 0.028). Multiple logistic regression analysis showed that one SNP (66292C>G) was significantly associated with chronic kidney disease (CKD: estimated creatinine clearance < 60 ml/min) in the recessive model (p = 0.0006). Our results suggest that genetic variations in XDH contribute partly to hypertension and its complications, including atherosclerosis and CKD.

Masked hypertension: subtypes and target organ damage.

Masked hypertension has been drawing attention recently because this condition is often seen in untreated and treated individuals and is associated with target organ damage and a poor cardiovascular prognosis. Although masked hypertension is defined as normal office blood pressure with elevated ambulatory or home blood pressure, there are several subtypes. Morning hypertension is the most common form of masked hypertension, and is caused by natural circadian variation, evening alcohol consumption, and the use of short-acting antihypertensive drugs. Daytime hypertension may be caused by lifestyle factors such as habitual smoking and mental or physical stress. Nighttime hypertension is seen in various conditions that produce non-dipping status, including a high salt intake, renal dysfunction, obesity, sleep apnea, and autonomic failure. Advanced target organ damage such as increases in the left ventricular mass, carotid artery intima-media thickness, and urinary albumin excretion, is often present both in untreated and treated subjects with masked hypertension. In our study, the presence of the reverse white-coat effect is independently associated with those indices of organ damage among treated hypertensive patients. It is important to identify individuals with masked hypertension, to evaluate them with including the search for the subtype, and to treat each patient appropriately according to the cause of this condition.

Brain natriuretic peptide in hemodialysis patients: predictive value for hemodynamic change during hemodialysis and cardiac function.

BACKGROUND: Though brain natriuretic peptide (BNP) is widely used as a clinical marker of cardiac function, there is considerable confusion in the interpretation of its value in hemodialysis (HD) patients whose BNPs are often elevated without cardiac diseases. The aim of the present study is to examine the predictive value of BNP for blood pressure (BP) fall during HD and cardiac function. METHODS: Subjects consisted of 205 (160 males, 45 females; age 66.5 +/- 10.5 years) consecutive uremic patients requiring maintenance HD who were admitted to our hospital during 2001-2004. One hundred and eleven cases had a history of ischemic heart disease. We measured BNP in all cases and collected clinical data including age, sex, duration of HD, blood examination and echocardiography. RESULTS: BNP of all 205 cases ranged from 6 to 16,097 pg/ml (median 831). During HD, the average BP change was -24.5 +/- 20.5 mm Hg, and 111 cases showed a systolic BP reduction >20 mm Hg. BNP did not predict the degree of BP fall. After adjusting confounding factors, the presence of ischemic heart disease, ultrafiltration rate, systolic BP before HD and serum sodium concentration showed a significant correlation with BP change (t = -2.84, -2.76, -4.68 and 2.90; p = 0.005, <0.01, <0.0001 and <0.005, respectively). In relation to echocardiographic indices, BNP >785 pg/ml could predict left ventricular dysfunction (fractional shortening of the left ventricle <30%, sensitivity 73%, specificity 65%). CONCLUSION: The level of BNP could not predict BP fall during HD. However, BNP is a good indicator of cardiac function even in uremic patients.

Relationship between insulin resistance and the renin-angiotensin system: analysis for patients with essential and renovascular hypertension.

Insulin resistance is frequently observed in patients with essential hypertension (EHT), and the renin-angiotensin system (RAS) has been demonstrated to modulate the status of insulin resistance. The aims of present study are to investigate the relationship between systemic RAS and insulin resistance in 82 patients with EHT and compare the impact of RAS to insulin resistance with 10 renovascular hypertension (RVHT) patients who have a highly activated systemic RAS. From patients who were admitted to our hospital, patients with overt diabetes and hypertensives who had secondary HT except RVHT or chronic renal failure were excluded. Plasma renin activity (PRA) was used as an indicator of systemic RAS activity. HOMA-R as an index of insulin resistance and sum of immunoreactive insulin (IRI) during glucose tolerance test (sigmaIRI) and IRI at 120 minutes (IRI120) were used as indices of hyperinsulinemia. In the EHT patients, circulating PRA showed an independent relationship with IRI120 and sigmaIRI after adjusting confounding factors (IRI120: t = 2.70, p = 0.01, sigmaIRI: t = 3.05, p < 0.001). Excluding patients who were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blocker (ARBs), the relationship remained in univariate linear regression; after adjustment for confounding factors, PRA showed a tendency to be correlated with sigmaIRI. However, there was no significant relationship between PRA and indices of insulin resistance and hyperinsulinemia in patients with RVHT. In conclusion, the systemic RAS may modulate insulin sensitivity in EHT patients.

The incidence and risk factors of renal artery stenosis in patients with severe carotid artery stenosis.

We previously showed that renal artery stenosis (RAS) was commonly found in patients with cardiovascular disease (CVD) such as myocardial infarction, stroke, or abdominal aneurysm. The aim of the present study was to evaluate the incidence and risk factors for RAS in patients with severe carotid artery stenosis (CAS) considered to need carotid endarterectomy. From February to August 2006, 41 consecutive patients with severe CAS were admitted to the Department of Neurosurgery of the National Cardiovascular Center. Each patient was examined for renal function and urinary albumin excretion, and renal artery duplex scanning was also performed. The patients were classified into two groups according to the findings of renal Doppler sonography, 11 patients with RAS and 30 patients without RAS. We evaluated the differences in clinical findings and renal function between the groups and clarified the risk factors for RAS. In RAS patients, smoking and incidence of other CVDs were evident, and renal function was impaired significantly compared with the patients without RAS. Multivariate logistic regression showed that the presence of other CVDs, renal function, and smoking were significant clinical predictors for RAS. In patients with severe CAS, RAS was frequently detected with the same frequency as ischemic heart disease. The RAS risk factors were the presence of other CVDs, renal dysfunction, and smoking. Since RAS is an underlying cause of hypertension and renal failure, it is important to consider the presence of RAS in patients with severe CAS.

Association of genetic polymorphisms of endothelin-converting enzyme-1 gene with hypertension in a Japanese population and rare missense mutation in preproendothelin-1 in Japanese hypertensives.

Endothelin-1 (EDN1), a 21-amino acid peptide, is a potent vasoconstrictor with various pharmacological responses. EDN1 is synthesized from a 212-amino acid precursor protein, preproEDN1, through multiple proteolytic steps. Endothelin-converting enzyme (ECE) cleaves a Trp73-Val74 peptide bond in big-EDN1 to give rise to mature EDN1. In this study, we examined the possible association of genetic variations in ECE1 with hypertension in a general Japanese population and searched for missense mutations in and around the EDN1 polypeptide. We genotyped 5 single nucleotide polymorphisms (SNPs) in the ECE1 gene in 1,873 individuals from a general Japanese population and identified one SNP associated with hypertension in women (rs212528: TT vs. TC+CC: odds ratio=1.40; 95% confidence intervals: 1.04-1.89; p=0.026), after adjusting for confounding factors. The systolic blood pressure in women with the CC genotype was 6.44 mmHg higher than that in those with the TT genotype (p=0.007), after adjusting for the same factors. Next, to identify the missense mutations that may influence the biological activity of EDN1, we sequenced the genomic region that encodes EDN1 in 942 Japanese hypertensive patients. We identified a novel missense mutation, G36R, in one hypertensive patient, but no mutations were observed in EDN1. A gene polymorphism in EDN1, Lys198Asn, has been reported to be associated with hypertension in obese subjects. Taken together, these findings reveal that the EDN-ECE pathway is an important system involved in essential hypertension in Japanese.