Hypertension with unilateral adrenal aldosterone and cortisol cosecreting adenoma: A case report.

Here, we report a case of unilateral adrenal aldosterone and cortisol co-secreting adenoma. A 34-year-old man with a history of severe hypertension for one year was detected hypokalemia (2.42 mmol/L lowest) and unilateral adrenal mass in a size of 71 mm*63 mm. Measurements of plasma aldosterone concentration and plasma renin activity showed marked increases. Primary aldosteronism was diagnosed. To exclude adrenal malignancy, the function of zona fasciculate was evaluated, and 24-h urine free cortisol was found abnormal in a testing. Further examinations revealed that circadian rhythm of serum cortisol disappeared and 2 mg-dexamethasone suppression test was positive. The final diagnosis was secondary hypertension, primary aldosteronism and subclinical Cushing's syndrome. After unilateral adrenalectomy, his blood pressure was normalized and biochemical parameters in the normal range. In conclusion, in patients with a large aldosterone-producing adenoma, the function of zona fasciculate might have to be evaluated for the identification of aldosterone and cortisol co-secreting neoplasms.

2019 Chinese Hypertension League guidelines on home blood pressure monitoring.

In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure.

Central aortic pressure improves prediction of cardiovascular events compared to peripheral blood pressure in short-term follow-up of a hypertensive cohort.

Objective: The aim of this study was to assess indices of a comprehensive panel of central aortic pressure and arterial stiffness for prediction of cardiovascular events in a hypertensive cohort.Methods: Noninvasive measurements of central aortic blood pressure, brachial pressure, wave reflection augmentation index, pressure amplification, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) were obtained in 675 hypertensive patients (age 61 ± 9 years, 425 males) for a mean follow-up period 25 ± 4 months. The primary endpoints were defined as cardiovascular disease (CVD) events or death from CVD.Results: After adjusting for confounding factors, central systolic (cSBP) and pulse pressure (cPP) showed higher hazard ratios (HR/10 mmHg) for cardiovascular events (CV) compared to peripheral pressure indices (pSBP, pPP) at age >60 years (cSBP: HR = 1.18, pSBP: HR = 1.17, p = 0.034; cPP: HR = 1.28, pPP: HR = 1.2, p = 0.019). Each SD increase in IMT and in central augmented pressure (cAP) entailed a 1.4 times higher risk of increased total events in elderly patients (age >60 years). For males, each SD increase in cAP was associated with 1.36 times higher risk of increased total events. For females, each SD increase in cAIx and cAP was associated with 0.4 and 0.5 times lower risk of increased total and major CV, respectively. This sex difference is most likely due to lack of age-related increase of cAIx in females after age >60 years compared to males.Conclusions: Central pressure improved prediction of CVD compared to peripheral pressure during a relatively short-term follow up of approximately 2 years at age >60 years.

Relationship between arterial stiffness and chronic kidney disease in patients with primary hypertension.

To investigate the association of noninvasive indices of arterial stiffness with chronic kidney disease (CKD) in patients with primary hypertension, 547 (mean age 60 years, 63% males) hypertensive hospital inpatients were recruited, comprising 337 hypertensives without CKD and 210 hypertensives with CKD. Noninvasive arterial stiffness indices were obtained, including central arterial haemodynamics derived from the radial artery waveform using SphygmoCor V8.0 system, carotid-femoral pulse wave velocity (cfPWV), large and small artery elasticity indices (C1, C2 respectively). Intima-media thickness (IMT) was evaluated by ultrasonography. The diagnosis of CKD was assessed by the estimated glomerular filtration rate (eGFR) or urinary albumin creatinine ratio (ACR). Compared with hypertension without CKD, hypertensive patients with CKD were older, had higher central systolic blood pressure, cfPWV, and IMT (all P < 0.01). With decreasing eGFR, cfPWV and augmentation index adjusted to heart rate of 75 bpm increased progressively whereas C2 decreased (P < 0.05) in subjects with CKD. In the overall population, cfPWV showed a significant trend of a negative association with eGFR (P = 0.04) after adjusting for age, gender, and brachial systolic blood pressure. Multiple logistic analysis showed that 1 SD (3 m/s) increase in cfPWV entailed a 1.35 (95% Cl: 1.018-1.790) times higher likelihood of the presence of CKD even after adjustment for confounding factors. The association of arterial stiffness and CKD suggests that cfPWV may be a potential hemodynamic index to evaluate cardiovascular risk in CKD patients with primary hypertension.

Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin II-induced cardiac diastolic dysfunction in mice.

AIM: To investigate whether apocynin, a NADPH oxidase inhibitor, produced cardioproteictive effects in Ang II-induced hypertensive mice, and to elucidate the underlying mechanisms. METHODS: C57BL/6 mice were subcutaneously infused Ang II for 4 weeks to mimic cardiac remodeling and fibrosis. Concomitantly the mice were administered apocynin (100 mg·kg(-1)·d(-1)) or/and the aldosterone receptor blocker eplerenone (200 mg·kg(-1)·d(-1)) via gavage for 4 weeks. Systolic blood pressure (SBP) and heart rate were measured, and transthoracic echocardiography was performed. For in vitro study, cardiac fibroblasts were treated with Ang II (10(-7) mol/L) in the presence of apocynin (10(-5) mol/L) or/and eplerenone (10(-5) mol/L). Immunohistochemistry and Western blotting were used to quantify the expression levels of NADPH oxidase and osteopontin (OPN) proteins in the cells. RESULTS: Both apocynin and eplerenone significantly decreased SBP, and markedly improved diastolic dysfunction in Ang II-induced hypertensive mice, accompanied with ameliorated oxidative stress and cardiac fibrosis. In the Ang II-treated cardiac fibroblasts, the expression levels of NOX4 and OPN proteins were markedly upregulated. Both Apocynin and eplerenone significantly suppressed the increased expression levels of NOX4 and OPN proteins in the Ang II-treated cells. In all the experiments, apocynin and eplerenone produced comparable effects. Co-administration of the two agents did not produce synergic effects. CONCLUSION: Apocynin produces cardioproteictive effects comparable to those of eplerenone. The beneficial effects of apocynin on myocardial oxidative stress and cardiac fibrosis might be mediated partly through a pathway involving NADPH oxidase and OPN.

Validation of the central blood pressure estimation by the SphygmoCor system in Chinese.

BACKGROUND: Pulse wave analysis using the SphygmoCor system allows the estimation of central blood pressures (BP). However, there is controversy over its accuracy for clinical use. METHODS: In 45 patients undergoing coronary angiography, we compared the ascending aorta BPs measured by the invasive catheter with the estimations by the SphygmoCor system, using paired t-tests, simple correlation analysis, and Bland-Altman plots. RESULTS: The estimation of central systolic BP by SphygmoCor was lower, although statistically insignificant, than that measured by the catheter (144±29 vs. 148±30 mmHg; P=0.98). The standard deviation of the difference amounted to 17 mmHg. Both the measured and estimated central systolic BPs were significantly (P<0.001) lower than the brachial systolic BP (156±30 mmHg). The diastolic BP measured at the brachial artery (87±15 mmHg) and provided by SphygmoCor (90±15 mmHg) were systematically higher (P<0.001) than that measured by the catheter (74±13 mmHg). The SphygmoCor system underestimated the central pulse pressure by -20±14 mmHg compared with the catheter method. The correlation coefficients for systolic BP, diastolic BP, and pulse pressure between catheter measurements and the SphygmoCor estimations were 0.84, 0.60, and 0.82 (P<0.001), respectively. CONCLUSION: When the radial waveform was calibrated with the oscillometric brachial pressures, the SphygmoCor system could not provide accurate estimation of central BPs. The inaccurate measurement of cuff pressure was the major limiting factor for the use of the transfer function in the clinical settings.

The association between transforming growth factor beta3 polymorphisms and left ventricular structure in hypertensive subjects.

BACKGROUND: Transforming growth factor beta (TGF-beta) may be a crucial regulator of cardiac remodeling. We investigated the association between the TGF-beta gene polymorphisms and left ventricular structure. METHODS: A total of 658 hypertensive subjects were genotyped for the TGF-beta1 T869C and TGF-beta3 (rs3917187 and rs4252338) polymorphisms. RESULTS: TGF-beta3 rs3917187 AA homozygotes had, while accounting for covariates, greater left ventricular end-systolic (LVESD, P=0.004) and end-diastolic dimension (LVEDD, P=0.007) than G allele carriers. Moreover, left ventricular mass index (LVMI) in AA genotype was 123.0+/-3.1g/m(2) significantly higher than that in AG (114.6+/-1.6g/m(2)) and GG (115.4+/-2.1g/m(2), P=0.03) genotypes. In multivariate regression analysis, TGF-beta3 rs3917187 genotype as an independent predictor had statistically significant effects on LVESD (beta=0.164, P=0.002), LVEDD (beta=0.172, P=0.003) and LVMI (beta=0.136, P=0.016), respectively. In further analyses, we observed a significant interaction between the rs3917187 and alcohol intake in relation to LVESD (P(int)=0.04) and left ventricular fractional shortening (LVFSH, P(int)=0.012). However, no relationship could be found between left ventricular parameters and the T869C or the rs4252338. CONCLUSION: The present results demonstrated that the TGF-beta3 rs3917187 polymorphism was associated with left ventricular structure, and had an interactive influence with alcohol on LVESD and LVFSH in hypertensive subjects.

[Incidence of metabolic disorders in patients with essential hypertension and patients with primary aldosteronism].

OBJECTIVE: To compare the incidence of metabolic disorders (MS) in patients with primary aldosteronism (PA) and essential hypertension (EH). METHODS: MS prevalence was observed in 200 EH patients (male 104) and 220 PA patients (male 117) hospitalized to our hospital from August 2005 to March 2007. RESULTS: (1) The prevalence of MS in PA group was significantly higher than that of EH group (47.3% vs. 31.5%, P = 0.009). (2) Blood pressure was significantly higher in PA group than that of EH [SBP: (150.67 +/- 15.45) mm Hg vs. (145.69 +/- 17.13) mm Hg, P = 0.042; DBP: (93.03 +/- 10.51) mm Hg vs. (85.83 +/- 14.44) mm Hg, P = 0.037]. (3) Incidences of abdominal obesity (86.8% vs. 78.5%, P = 0.024) and insulin resistance (insulin sensitivity index: 42.42 +/- 16.11 vs. 49.58 +/- 22.43, P = 0.008) were significantly higher in PA group than in EH group. CONCLUSION: The prevalence of MS in hospitalized PA patients was significantly higher than that of EH patients characterized by prevalent abdominal obesity, insulin resistant and severe hypertension.

Association between genetic variation in transforming growth factors beta1 and beta3 and renal dysfunction in non-diabetic Chinese.

Genetic variants of transforming growth factor (TGF) beta1 have been reported to be associated with diabetic nephropathy. Few studies investigated polymorphisms in the TGF-beta1 and TGF-beta3 genes in relation to renal dysfunction in non-diabetic subjects. In all, 601 non-diabetic Chinese were genotyped for the TGF-beta1 T869C and TGF-beta3 IVS3-98G>A polymorphisms by PCR-restriction fragment length polymorphism and real-time allele-specific PCR, respectively. Renal dysfunction was defined as a predicted glomerular filtration rate (GFR) of 60mL/min/1.73m(2) or less. 24-hour urinary albumin excretion was measured by an immunonephelometric assay in 352 hypertensive subjects. Our study sample included 184 (30.6%) women, 396 (65.9%) hypertensive patients (65.9%), and 94 (15.6%) patients with renal dysfunction. In men but not women, the TGF-beta1 TC genotype was significantly (p = 0.0005) overrepresented in patients with renal dysfunction (52.2% vs 36.8% in subjects with normal renal function). Accordingly, in men, with adjustment for age, body mass index, and systolic and diastolic blood pressure, serum creatinine concentration was significantly (p < or = 0.03) higher in the TC heterozygotes than TT and CC homozygotes. Furthermore, in 231 male hypertensive patients, with similar adjustments applied, 24-hour urinary albumin excretion was significantly (p = 0.02) higher in the IVS3-98 AA homozygotes than G allele carriers. In further multivariate regression analysis, only in men, TGF-beta1 and TGF-beta3 genotypes as independent predictors had statistically significant effect on serum creatinine (p = 0.007) and urinary albumin excretion (p = 0.022), respectively. Our study demonstrated the associations of genetic variants in the TGF-beta genes with renal dysfunction and albuminuria in non-diabetic Han Chinese men but not women.

[Association of aldosterone synthase gene -344T/C polymorphism with plasma aldosterone and angiotensin II concentration in hypertensive patients].

OBJECTIVE: To investigate the association of aldosterone synthase (CYP11B2) -344T/C polymorphism with plasma renin activity (PRA), and concentrations of angiotensin II (Ang II) and aldosterone (Aldo) in patients with essential hypertension (EH). METHODS: 421 EH patients, 296 males and 125 females, aged 56.3 +/- 11.2, and 207 sex and aged-matched normotensive subjects were genotyped for the CYP11B2 -344T/C polymorphism by polymerase chain reaction-restriction fragment length polymorphism. PRA and plasma Ang II and Aldo concentrations were measured by radioimmunoassay among 328 EH patients in the supine position and 279 of the 328 subjects in the upright position. RESULTS: No significant difference in genotype and allele frequencies of CYP11B2 -344T/C polymorphism was observed between the EH and normotensive subjects (P = 0.61 and P = 0.34 respectively). In the 328 EH patients undergoing measurement of PRA, Ang II, and Aldo, the plasma Aldo concentration of the TT subjects was 76.8 pg/ml, significantly higher than those of the TC subjects (58.8 pg/ml) and CC subjects (58.8 pg/ml, P = 0.02), after adjustment for age, sex and body mass index. No association was found between the -344T/C polymorphism and PRA and plasma Ang II in the supine position (P = 0.63 and P = 0.28 respectively). However, with similar adjustment applied, the plasma Ang II concentration in the upright position was higher in the CC subjects (85.7 pg/ml) than in the TC subjects (54.6 pg/ml) and TT subjects (51.8 pg/ml. P = 0.02). CONCLUSION: In the EH patients, CYP11B2 -344T/C polymorphism is associated with plasma Aldo and the plasma Ang II concentration when the patients are in the upright position.

[Single nucleotide polymorphisms of three candidate genes in essential hypertension].

OBJECTIVE: To explore the association of single nucleotide polymorphisms (SNPs) of three candidate genes, including T869C of transforming growth factor beta1 (TGF-beta1), -344T/C of aldosterone synthase (CYP11B2) and Gly460Trp of alpha-Adducin with essential hypertension in Chinese Han population. METHODS: Three hundred ninety six hypertensive patients and 214 normotensive subjects were genotyped for T869C, -344T/C and Gly460Trp polymorphisms with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mutagenically separated PCR (MS-PCR), respectively. RESULTS: In single-gene analysis, no association was observed between either CYP11B2 -344T/C or alpha-Adducin Gly460Trp polymorphism and essential hypertension. For female, there were significant difference in genotype distribution and allele frequency of T869C polymorphism (P < 0.02), as compared with subjects with T allele. CC homozygosity had a higher relative risk of hypertension (OR = 2.97, 95% CI, 1.38 to 6.32, P = 0.004), whereas we failed to detect any association between T869C polymorphism and essential hypertension in male. In multiple-gene analysis, the incidence of hypertension was higher in CYP11B2 TT homozygosity than in other CYP11B2 genotypes (OR = 1.99, 95% CI, 1.01 to 3.74, P = 0.03) in the presence of TGF-beta1 CC genotype. CONCLUSIONS: Our results indicated that T869C polymorphism of TGF-beta1 gene might be associated with essential hypertension in female, furthermore, the TGF-beta1 T869C and CYP11B2-344T/C polymorphisms appeared to interact in hypertensive population.

[Aldosterone-to-renin ratio threshold for screening primary aldosteronism in Chinese hypertensive patients].

OBJECTIVE: In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become a most effectively and commonly used method for screening primary aldosteronism from hypertensive patients. It is known that there is a large variance in ARR value between races and ARR is affected by many factors, such as drugs, posture and serum potassium etc. The objective of this study is to establish the threshold of ARR for screening primary aldosteronism in Chinese hypertensive patients. METHODS: A total of 110 hypertensive patients were recruited and divided into essential hypertension group (n=65) and adenoma/hyperplasia group (n=45) according to the adrenal contrast CT scan. Antihypertensive drugs which can affect ARR such as beta-blockers, dihydropyridine calcium channel blockers (CCBs), ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and clonidine, were withdrawn for at least 2 weeks. Washout period for diuretics including spironolactone were 4 weeks. Non-dihydropyridine calcium channel blockers (slow released verapamil) and/or alpha-blocker (terazosin) are allowed for controlling blood pressure when needed. If the serum potassium value<3.6 mmol/L, an oral potassium supplement was prescribed. After keeping upright position for 2 hours, blood samples were drawn for PRA and PAC measurement between 9:00AM-10:00AM. RESULTS: ARR was 100.00+/-48.65 (14.19-285.16) pg/ml vs ngxml-1xh-1 in patients with essential hypertension and 699.33+/-213.33 (185.8-2150) pg/ml vs ngxml-1xh-1 in patients with adenoma/hyperplasia. ARR value was greater than 240 in 42 out of 45 patients (93.3%) with adenoma/hyperplasia and was less than 240 in 59 out of 65 (90.7%) patients with essential hypertension. We used ARR 240 as the cut-off threshold for screening primary aldosteronism in another 178 hypertensive patients and ARR was greater than 240 in all 15 patients with confirmed primary aldosteronism. CONCLUSION: It is suitable to use upright ARR 240 as a cut-off threshold for screening primary aldosteronism in Chinese hypertensive patients.

[No association between 3 polymorphisms of transforming growth factor beta3 gene and essential hypertension in Chinese].

OBJECTIVE: To investigate possible association between the single nucleotide polymorphisms (SNPs) of transforming growth factor beta3 (TGF-beta3) gene and essential hypertension (EH) in Chinese. METHODS: The promoter region, exons, as well as part of the introns of TGF-beta3 gene were sequenced by a fluorescent labeling automatic sequencing method to detect and characterize the SNPs in 24 DNA samples from a Chinese population. Then we conducted a case-control study using 396 patients with hypertension (case) and 214 nomortensive subjects (control). The three SNPs including Thr63Asn, SS5608219 and SS5608220 were genotyped by PCR-RFLP or real-time allele-specific PCR in subjects studied. RESULTS: Seven SNPs in the exons, introns and 3'untranslated region (3'UTR) of TGF-beta3 gene were identified. Among them, 2 SNPs were found to be novel genetic variants and one of the two located in the exon 1 and produced substitution of amino acid. However, no differences were found between hypertensives and nomortensives in genotype distribution and allele frequency of SS5608219, Thr63Asn or SS5608220 polymorphisms. CONCLUSIONS: Two novel SNPs of TGF-beta3 gene were identified in Chinese. One of them produces a threonine to asparagines substitution in codon 63 (Thr63Asn). But no association was found between TGF-beta3 gene polymorphisms and EH in Chinese.

[Insulin secretion and insulin sensitivity in 1193 inpatients with essential hypertension].

OBJECTIVE: To evaluate the metabolic profiles of insulin secretion and insulin sensitivity in different categories of nondiabetic patients with essential hypertension, we made a retrospecting study in our hospital. METHODS: According to the criteria of WHO and ADA, we calculated the distribution of plasma glucose levels during a 75 g oral glucose tolerance test (OGTT). Nondiabetic subjects with hypertension were classified into the following four groups: (1) normal glucose tolerance (NGT) with fasting plasma glucose (FPG) < 6.1 mmol/L and 2h-plasma glucose (2hPG) < 7.8 mmol/L, (2) Isolate impaired fasting glucose (IFG) with FPG 6.1-7 mmol/L and 2hPG < 7.8 mmol/L, (3) Isolate impaired glucose tolerance (IGT) with FPG < 6.1 mmol/L and 2hBG 7.8-11.1 mmol/L, (4) impaired fasting glucose and impaired glucose tolerance (IFG/IGT) with FPG 6.1-7 mmol/L and 2hBG 7.8-11.1 mmol/L. Then we divided the groups of NGT and IGT based on the normal 30 or 60 minute plasma glucose level during OGTT respectively. 30 minute plasma glucose level < 11.1 mmol/L and 60 minute plasma glucose level < 10.5 mmol/L were considered to be normal. HOMA-IR (insulin resistance) and composite ISI (insulin sensitivity index) were used to estimate insulin resistance and HOMA-beta and DeltaI/DeltaG index to estimate insulin secretion. RESULTS: 11.1% of the 1193 subjects were newly diagnosed diabetic patients, in whom 57.9% had isolated postchallenge hyperglycemia only. In the IGT and IFG/IGT groups, HOMA-IR were significantly higher than that in the NGT group, whereas composite ISI and DeltaI/DeltaG were significantly lower than that in the NGT group. Whether 30 or 60 minute plasma glucose level was high or not, composite ISI in IGT group was significantly lower than that in the NGT group. In the NGT group, DeltaI/DeltaG in subjects with high 30 or and 60 minute plasma glucose level was significantly lower than that in subjects with normal 30 and 60 minute plasma glucose level. CONCLUSIONS: Subjects with IGT or IFG/IGT have both impaired insulin sensitivity and insulin secretion. In the NGT group, subjects with high 30 or/and 60 minute plasma glucose level have impaired beta-cell function.