Obstructive sleep apnea in relation to beat-to-beat, reading-to-reading, and day-to-day blood pressure variability.

We investigated blood pressure (BP) variability as assessed by beat-to-beat, reading-to-reading and day-to-day BP variability indices in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). In 786 hospitalized hypertensives (mean age, 53.2 years; 42.2% women), we performed 10-min beat-to-beat (n = 705), 24-h ambulatory (n = 779), and 7-day home BP (n = 445) measurements and the full overnight polysomnography. Mild, moderate and severe OSAHS were defined as an apnea-hypopnea index of 5-14, 15-29, and ≥ 30 events per hour, respectively. BP variability indices including variability independent of the mean (VIM), average real variability (ARV), and maximum-minimum difference (MMD), were compared across the OSAHS severity groups. In univariate analysis, beat-to-beat systolic VIM and MMD, reading-to-reading asleep systolic and diastolic ARV and MMD increased from patients without OSAHS, to patients with mild, moderate and severe OSAHS. This increasing trend for beat-to-beat systolic VIM and MMD remained statistically significant after adjustment for confounders (P ≤ 0.047). There was significant (P ≤ 0.039) interaction of the presence and severity of OSAHS with age and body mass index in relation to the beat-to-beat systolic VIM and MMD and with the presence of diabetes mellitus in relation to asleep systolic ARV. The association was stronger in younger (age < 50 years) and obese (body mass index ≥ 28 kg/m²) and diabetic patients. None of the day-to-day BP variability indices reached statistical significance (P ≥ 0.16). BP variability, in terms of beat-to-beat systolic VIM and MMD and asleep reading-to-reading asleep systolic ARV, were higher with the more severe OSAHS, especially in younger and obese and diabetic patients.

Non-invasive left ventricular pressure-strain loop study on cardiac fibrosis in primary aldosteronism: a comparative study with cardiac magnetic resonance imaging.

We investigated the potential diagnostic value of the myocardial work indices based on speckle tracking echocardiography for cardiac fibrosis in patients with primary aldosteronism. Our observational study included 48 patients with primary aldosteronism. We performed conventional echocardiography and the left ventricular pressure-strain loop analysis. We also performed cardiac magnetic resonance imaging to evaluate cardiac replacement fibrosis defined as late gadolinium enhancement (LGE). Patients with LGE (n = 30, 62.5%) had longer duration of hypertension and higher plasma NT-proBNP than those without LGE. Besides, they had a significantly (P ≤ 0.04) higher left ventricular mass index (121.3 ± 19.5 vs. 103.3 ± 20.0 g/m2) and global wasted work (205 ± 78 vs. 141 ± 36 mmHg%) and lower global longitudinal strain (-17.7 ± 1.8 vs. -19.0 ± 2.4%) and work efficiency (GWE, 90.9 ± 2.4 vs. 93.8 ± 1.5%). Receiver Operating Characteristics analysis showed that GWE ≤ 92% had a sensitivity and specificity of 76.7% and 83.3%, respectively, for LGE with the area under curve 0.85 (P < 0.001). In conclusion, both cardiac structure and function were impaired in patients with primary aldosteronism and cardiac fibrosis. The myocardial work index GWE showed significant value for the indication of cardiac fibrosis. Characterization of cardiac fibrosis in primary aldosteronism and the detective value of clinical and echocardiographic indices. Cardiac fibrosis was presented in 30 of the 48 analyzed primary aldosteronism patients with focal high signal intensity in mid-layer myocardium in limited segments as its characterization. The global work efficiency (GWE) had a significantly higher detective value for myocardial replacement fibrosis than other measurements such as left ventricular mass index (LVMI) and NT-proBNP.

Seasonality in nighttime blood pressure and its associations with target organ damage.

There is some evidence that nighttime blood pressure varies between seasons. In the present analysis, we investigated the seasonal variation in ambulatory nighttime blood pressure and its associations with target organ damage. In 1054 untreated patients referred for ambulatory blood pressure monitoring, we performed measurements of urinary albumin-to-creatinine ratio (ACR, n = 1044), carotid-femoral pulse wave velocity (cfPWV, n = 1020) and left ventricular mass index (LVMI, n = 622). Patients referred in spring (n = 337, 32.0%), summer (n = 210, 19.9%), autumn (n = 196, 18.6%) and winter (n = 311, 29.5%) had similar 24-h ambulatory systolic/diastolic blood pressure (P ≥ 0.25). However, both before and after adjustment for confounding factors, nighttime systolic/diastolic blood pressure differed significantly between seasons (P < 0.001), being highest in summer and lowest in winter (adjusted mean values 117.0/75.3 mm Hg vs. 111.4/71.1 mm Hg). After adjustment for confounding factors, nighttime systolic/diastolic blood pressure were significantly and positively associated with ACR, cfPWV and LVMI (P < 0.006). In season-specific analyses, statistical significance was reached for all the associations of nighttime blood pressure with target organ damage in summer (P ≤ 0.02), and for some of the associations in spring, autumn and winter. The association between nighttime systolic blood pressure and ACR was significantly stronger in patients examined in summer than those in winter (standardized ß, 0.31 vs 0.11 mg/mmol, P for interaction = 0.03). In conclusion, there is indeed seasonality in nighttime blood pressure level, as well as in its association with renal injury in terms of urinary albumin excretion. Our study shows that there is indeed seasonal variability in nighttime blood pressure, highest in summer and lowest in winter, and its association with renal injury in terms of urinary albumin excretion varies between summer and winter as well.

Role of α1-blockers in the current management of hypertension.

There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1-blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1-blockers as add-on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1-blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1-blockers have to be used under several considerations. Among the currently available agents, only long-acting α1-blockers, such as doxazosin gastrointestinal therapeutic system 4-8 mg daily and terazosin 2-4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1-blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1-blocker with a diuretic.

A Prospective Comparative Study on Cardiac Alterations After Surgery and Drug Treatment of Primary Aldosteronism.

Background: Current guideline recommends both surgery and drug treatment for primary aldosteronism. Treatment effects on the cardiac structure and function remain under investigation. Objective: We performed a prospective study in patients with primary aldosteronism to compare effects of surgery and drug treatment on the cardiac structure and function as assessed by the left ventricular (LV) pressure-strain loop, a novel echocardiographic technique that incorporates myocardial deformation and LV pressure. Methods: Our study included 39 and 28 patients treated with surgery and a mineralocorticoid antagonist, respectively. We performed conventional and speckle tracking echocardiography at baseline and 3 and 6 months of follow-up. Results: During follow-up, both surgery and drug treatment normalized serum potassium concentration and significantly reduced blood pressure. Both treatments significantly and similarly decreased LV mass index and left atrial volume index. However, only in the surgery group did global wasted work significantly decrease (200.8 ± 86.7 at baseline vs. 142.1 ± 58.1 mmHg% at 6 months) and global work efficiency (91.5 ± 3.1 vs. 93.6 ± 2.3%) and global longitudinal strain (-18.3 ± 2.7 vs. -19.2 ± 1.9%) significantly (p < 0.01) increase at 6 months of follow-up. The corresponding differences from the changes in the drug treatment group were 39.5 mmHg% (95% CI, 17.1, 62.0 mmHg%), -1.64% (95% CI, -2.56, -0.71%), and -0.85% (95% CI, -1.51, -0.20%), respectively. In addition, the changes in global wasted work at 6 months of follow-up was significantly correlated with that in 24-h urinary aldosterone excretion in the drug treatment group (r = 0.54) and two groups combined (r = 0.55), but not the surgery group. Conclusion: In spite of similar serum potassium normalization and blood pressure control, surgical removal of an adrenal gland, but not mineralocorticoid receptor antagonism, showed early improvement in cardiac function.

A non-invasive left ventricular pressure-strain loop study on myocardial work in primary aldosteronism.

We investigated the myocardial work derived from left ventricular pressure-strain loop in patients with primary aldosteronism or primary hypertension. We enrolled 50 patients with primary aldosteronism, 50 age- and sex-matched patients with primary hypertension, and 25 normotensive control subjects. We performed transthoracic echocardiography and speckle-tracking echocardiography-based left ventricular pressure-strain loop analysis to evaluate cardiac structure and function. Patients with primary aldosteronism and those with primary hypertension had similar clinic and ambulatory blood pressures, except that the former had a significantly (P = 0.03) higher nighttime systolic blood pressure. All subjects had normal left ventricular ejection fraction (66.4 ± 4.7%). Patients with primary aldosteronism had a greater left ventricular mass index than those with primary hypertension and the normal controls (111.0 ± 21.6 g/m2 versus 95.7 ± 17.7 and 77.9 ± 13.5 g/m2, respectively, P < 0.001). The global myocardial work index (GWI, 2336 ± 333, 2366 ± 288, and 2292 ± 249 mmHg%, respectively), and global constructive work (GCW, 2494 ± 325, 2524 ± 301, and 2391 ± 193 mmHg%, respectively), were comparable in the three groups (P ≥ 0.18). However, the global work efficiency (GWE) differed significantly (P < 0.001), being lowest in primary aldosteronism (91.1 ± 2.7%), intermediate in primary hypertension (93.5 ± 2.5%) and highest in controls (95.3 ± 1.5%). The opposite was true for the global wasted work (GWW) (205.6 ± 74.6, 142.0 ± 56.4 and 99.4 ± 33.7 mmHg%, respectively, P < 0.001). GWE was significantly correlated with the logarithmically transformed plasma concentration and the urinary excretion of aldosterone in patients with primary aldosteronism or primary hypertension (r = -0.43 for both, P < 0.001). The associations remained statistically significant (P ≤ 0.04) after further adjustment for several factors, including left ventricular mass index and clinic or nighttime blood pressure. In conclusion, GWE decreased and GWW increased in primary hypertension and further in primary aldosteronism, probably because of the adrenal aldosterone hypersecretion and the left ventricular mass index increase, while GWI and GCW were similar, indicating that similar and normalized total myocardial work might be a compensation in hypertension at the expense of work efficiency.

Continuous positive airway pressure adherence and blood pressure lowering in patients with obstructive sleep apnoea syndrome and nocturnal hypertension.

PURPOSE: We investigated continuous positive airway pressure (CPAP) adherence and its association with the blood pressure (BP) and pulse rate changes in patients with obstructive sleep apnoea syndrome (OSAS) and hypertension. MATERIALS AND METHODS: In a single-blind trial, patients were randomly assigned to CPAP or sham CPAP treatment for 3 months. We performed clinic, ambulatory and home BP measurements at baseline and during follow-up. CPAP adherence was assessed as the CPAP frequency per week and time per night. Non-adherence was defined as a CPAP use for <5 days/week or <4 h/night. RESULTS: In the CPAP (n = 26) and sham CPAP groups (n = 21), the CPAP frequency was 5.5 and 4.8 days/week (p = 0.17), respectively, and the CPAP time was 5.0 and 4.1 h/night (p = 0.03), respectively. The corresponding prevalence of non-adherence was 46.2% and 66.7% (p = 0.16), respectively. The CPAP frequency but not time tended to be associated with the changes in BP and pulse rate at 3 months of follow-up, especially home systolic/diastolic BP in the CPAP group (3.2/1.3 mmHg greater reductions per 1 day increment, p ≤ 0.01). Adherent, compared with non-adherent patients, had greater reductions in BP or pulse rate at 3 months of follow-up. In the CPAP and sham CPAP groups combined, statistical significance was achieved for the adjusted between adherence and non-adherence differences in home systolic/diastolic BP (-5.0/-3.8 mmHg) and 24-h, daytime and night-time ambulatory pulse rate (-6.2, -7.8 and -4.4 beats/min, respectively, p ≤ 0.04). CONCLUSION: CPAP adherence was associated with the BP lowering and pulse rate slowing effects, especially the CPAP frequency.

Renal Sodium Handling in Relation to Environmental and Genetic Factors in Untreated Chinese.

BACKGROUND: We investigated proximal and distal renal tubular sodium handling, as assessed by fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa), in relation to environmental and genetic factors in untreated patients. METHODS: Our study participants were suspected hypertensive patients being off antihypertensive medication for ≥2 weeks and referred for 24-hour ambulatory blood pressure monitoring. We collected serum and 24-hour urine for measurement of sodium, creatinine, and lithium concentration, and calculated FELi and FDRNa. We genotyped 19 single-nucleotide polymorphisms associated with renal sodium handling or blood pressure using the ABI SNapShot method. RESULTS: The 1,409 participants (664 men, 47.1%) had a mean (±SD) age of 51.0 ± 10.5 years. After adjustment for host factors, both FELi and FDRNa were significantly (P ≤ 0.01) associated with season and humidity, explaining ~1.3% and ~3.5% of the variance, respectively. FELi was highest in autumn and lowest in summer and intermediate in spring and winter (P = 0.007). FDRNa was also highest in autumn but lowest in winter and intermediate in spring and summer (P < 0.001). Neither FELi nor FDRNa was associated with outdoor temperature or atmospheric pressure (P ≥ 0.13). After adjustment for host and environmental factors and Bonferroni multiple testing, among the 19 studied genetic variants, only rs12513375 was significantly associated with FELi and FDRNa (P ≤ 0.004) and explained about 1.7% of the variance. CONCLUSIONS: Renal sodium handling as measured by endogenous lithium clearance was sensitive to major environmental and genetic factors. Our finding is toward the use of these indexes for the definition of renal tubular dysfunction.

A speckle tracking echocardiographic study on right ventricular function in primary aldosteronism.

OBJECTIVE: We investigated right ventricular function using speckle tracking echocardiography (STE) in patients with primary aldosteronism. METHODS: Our study included 51 primary aldosteronism patients and 50 age and sex-matched primary hypertensive patients. We performed two-dimensional echocardiography to measure cardiac structure and function. We performed STE offline analysis on right ventricular four-chamber (RV4CLS) and free wall longitudinal strains (RVFWLS). RESULTS: Primary aldosteronism patients, compared with primary hypertensive patients, had a significantly (P ≤ 0.045) greater left ventricular mass index (112.0 ±â€Š22.6 vs. 95.8 ±â€Š18.5 g/m) and left atrial volume index (26.9 ±â€Š6.0 vs. 24.7 ±â€Š5.6 ml/m) and higher prevalence of left ventricular concentric hypertrophy (35.3 vs. 12.0%), although they had similarly normal left ventricular ejection fraction (55-77%). Primary aldosteronism patients also had a significantly (P ≤ 0.047) larger right atrium and ventricle, lower tricuspid annular plane systolic excursion, and higher E/E't (the peak early filling velocity of trans-tricuspid flow to the peak early filling velocity of lateral tricuspid annulus ratio), estimated pulmonary arterial systolic pressure and right ventricular index of myocardial performance. On the right ventricular strain analysis, primary aldosteronism patients had a significantly (P < 0.001) lower RV4CLS (-18.1 ±â€Š2.5 vs. -23.3 ±â€Š3.4%) and RVFWLS (-21.7 ±â€Š3.7 vs. -27.9 ±â€Š4.5%) than primary hypertensive patients. Overall, RV4CLS and RVFWLS were significantly (r = -0.58 to -0.41, P < 0.001) correlated with plasma aldosterone concentration and 24-h urinary aldosterone excretion. After adjustment for confounding factors, the associations for RV4CLS and RVFWLS with 24-h urinary aldosterone excretion remained significant (P < 0.001), with a standardized coefficient of -0.48 and -0.55, respectively. CONCLUSION: In addition to left ventricular abnormalities, primary aldosteronism patients also show impaired right ventricular function, probably because of hyperaldosteronism.

Subtypes of masked hypertension and target organ damage in untreated outpatients.

Purpose: Masked hypertension (MHT) is characterised as an office normotension in the presence of out-of-office hypertension, and can be further categorised as isolated daytime (dMHT), night-time (nMHT) or day-night MHT (dnMHT) according to the time when hypertension is present. MHT is associated with adverse cardiovascular outcome. However, no previous studies contrasted these MHT subtypes in their associations with target organ damage (TOD).Materials and methods: Consecutive untreated patients referred for ambulatory blood pressure (BP) monitoring to our Hypertension Clinic were recruited. Office and ambulatory BPs were measured using the Omron 7051 and SpaceLabs 90217 monitors, respectively. The BP thresholds of daytime and night-time hypertension were of ≥135/85 mmHg and ≥120/70 mmHg, respectively. We performed various TOD measurements, including carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), left ventricular mass index (LVMI) and E/E', estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR).Results: The 1808 participants (mean age, 51 years; women, 52%) included 672 (37.2%) MHT subjects, among whom 123 (18.3%) had dMHT, 78 (11.6%) nMHT, and 471 (70.1%) dnMHT. In all participants as well as patients with office normotension (n = 1222), ambulatory daytime and night-time BPs were similarly associated with all TOD measurements (p ≥ 0.20) after multivariate adjustment. Compared to normotensive subjects (p < 0.05), patients with dMHT had faster cfPWV (7.81 vs. 7.58 m/s) and thicker cIMT (637.6 vs. 610.4 µm), patients with nMHT had thicker cIMT (641.8 vs. 610.4 µm) and increased UACR (0.79 vs. 0.59 mg/mmol), and patients with dnMHT had all worse TOD measures mentioned-above plus elevated eGFR (120.7 vs. 116.8 ml/min/1.73m2).Conclusion: MHT was associated with TOD irrespective of subtype, although TOD varied slightly across these subtypes. The study highlights the importance of controlling both daytime and night-time BP in hypertensive patients.

Left atrial myocardial dysfunction in patients with primary aldosteronism as assessed by speckle-tracking echocardiography.

BACKGROUND: We investigated the left atrial myocardial deformation in patients with primary aldosteronism using the speckle-tracking echocardiographic (STE) strain imaging technique. METHODS: Our study included 107 primary aldosteronism patients [52 aldosterone-producing adenoma (APA) and 55 idiopathic hyperaldosteronism (IHA)] and 50 primary hypertensive patients. We performed conventional echocardiography to measure left atrial volume and ejection fraction, and STE to estimate left atrial myocardial deformation including peak velocity, strain and strain rate and calculate the ratio of E/e' to left atrial strain during left ventricular systole as the left atrial stiffness index. RESULTS: Patients with APA, compared with those with IHA and primary hypertension had a significantly (P < 0.001) lower serum potassium concentration and higher 24-h urinary aldosterone excretion and plasma aldosterone-to-renin ratio. Patients with APA had a significantly (P < 0.01) larger maximal, precontraction, and minimal left atrial volumes and lower total, active and passive left atrial emptying fractions than those with IHA and primary hypertension. Among the three groups, patients with APA showed lowest left atrial velocity, strain, and strain rate during ventricular systole, early diastole and late diastole (P < 0.05) and highest left atrial stiffness index (P < 0.001). In unadjusted analysis, the left atrial strain, strain rate and stiffness index were significantly (P < 0.05) associated with plasma aldosterone concentration and urinary aldosterone excretion. After adjustment for various confounding factors, these associations remained statistically significant for urinary aldosterone excretion (P < 0.05) but not plasma aldosterone concentration (P ≥ 0.05). CONCLUSION: Patients with primary aldosteronism, especially APA, had impaired left atrial deformation mechanics and increased left atrial stiffness, providing a promising insight into early detection of subclinical left atrial dysfunction by strain echocardiography.

Short-term reproducibility of the 24-h ambulatory monitoring of brachial and central hemodynamics in untreated Chinese.

Objective: Advanced technology allows non-invasive monitoring of the 24-h brachial and central hemodynamics simultaneously. However, related reproducibility data was limited in White patients. We therefore explored if the novel measurements would be reproducible in Chinese. Methods: From February 2017 to January 2018, 152 untreated patients who were suspected of hypertension and referred for ambulatory blood pressure (BP) monitoring were recruited. Ambulatory BP monitoring was repeated within one month (median, 12.5 days) using the Mobil-O-Graph monitors (IEM, Germany). Reproducibility was assessed as the intra-class correlation coefficient (ICC), coefficient of variation (CV), and repeatability coefficient (RC). Results: The 152 participants (average age, 58.6 years) included 54 men and 98 women. The first and second means of the ambulatory brachial and central BPs, pulse wave velocity (PWV), augmentation pressure, augmentation index (AIx) and AIx at a heart rate of 75 beats per minute (AIx@75) were all similar (p ≥ 0.065), except that the repeated daytime and 24-h brachial and central systolic BPs and pulse pressure slightly differed by approximately 1-2 mmHg (p ≤ 0.011). ICC ranged from 0.70 to 0.94 for all ambulatory BPs and ≥0.91 for the arterial measurements. CV was in the range from 5.0% to 10.3% for all BPs and PWV measurements, and from 15.5% to 22.3% for AIx and AIx@75. RC expressed as percentages of maximal variation was <15% for the PWVs and ranged from 25.5% to 54.7% for BPs, AIx and AIx@75. Conclusions: The 24-h ambulatory brachial and central BPs and arterial measurements were reproducible within a short time period in Chinese, and could therefore be used in clinical practice and research settings.

Comparison Between Home and Ambulatory Morning Blood Pressure and Morning Hypertension in Their Reproducibility and Associations With Vascular Injury.

Morning blood pressure (BP) is recommended to be assessed by either 24-hour ambulatory or home BP monitoring. By which methods morning BP assessed is more reproducible and more closely associated with vascular injury remains unknown. We, therefore, addressed this issue in 1049 referred untreated outpatients (51.9% women; average age, 51 years) who had performed 24-hour ambulatory and 7-day home BP monitoring and vascular evaluations. Irrespective of the assessment methods, morning BPs were all significantly ( P≤0.027) associated with the arterial measures. The partial correlation coefficients of carotid-femoral pulse wave velocity and urinary albumin-to-creatinine ratio with home morning BPs were greater than those with the ambulatory morning pressures among the first 2 hours after awakening (0.21-0.37 versus 0.15-0.24; P<0.05). The associations with home morning systolic BP remained significant ( P≤0.002) after full adjustment for evening BP, whereas those with ambulatory morning BPs became nonsignificant after full adjustment for 24-hour BP except that of the carotid-femoral pulse wave velocity with ambulatory morning (6:00-10:00) systolic BP. Of the 135 subjects who had both home and repeated 24-hour ambulatory BP monitoring within 1 month, the coefficients of variation were ≈11% for ambulatory morning BPs and 5% for home self-measurements. In conclusion, morning BP, irrespective of the assessment methods and definitions, was generally reproducible and significantly associated with vascular indices. Nevertheless, home morning BP might be preferred than ambulatory measurements because of better reproducibility and stronger correlation with vascular indices.

Left ventricular deformation in relation to the geometric pattern in hypertensive patients.

This study aimed to evaluate left ventricular deformation in relation to the geometric pattern in hypertensive patients with normal left ventricular ejection fraction using speckle tracking echocardiography (STE).Transthoracic echocardiography was performed in 80 hypertensive patients and 50 age- and gender-matched normotensive subjects. Left ventricular geometric pattern was defined according to left ventricular mass index and relative wall thickness as normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy, respectively. Quantitative measurements of longitudinal, circumferential, and radial strain were performed for endocardial, middle, and epicardial layers of the left ventricular wall at each segment.The longitudinal strain in hypertension was lower for all 3 layers in concentric (n = 20) and eccentric hypertrophy (n = 20) than normotensive subjects (n = 50, P < .01). It was also significantly lower for the endocardial layer in concentric remodeling (n = 20, P = .04 vs normotensive subjects). The circumferential strain in hypertension was higher in normal geometry or concentric remodeling, lower in concentric hypertrophy, and at similar level in eccentric hypertrophy, in comparison with normotensive subjects. The difference from normotensive subjects was statistically significant for the endocardial and middle layers in normal geometry (P < .03), for the endocardial layer in concentric remodeling (P < .02), and for the middle and epicardial layers in concentric hypertrophy (P≤.001). The radial strain and twist did not differ between normotensive and hypertensive subjects (P > .08).Left ventricular deformation in hypertension occurs with various geometric patterns disproportionately in the endocardial, middle and epicardial layers and differently in the longitudinal and circumferential orientations.

Speckle-Tracking Echocardiographic Layer-Specific Strain Analysis on Subclinical Left Ventricular Dysfunction in Patients With Primary Aldosteronism.

BACKGROUND: Primary aldosteronism (PA) may cause myocardial injury. We investigated myocardial dysfunction using speckle-tracking echocardiographic (STE) layer-specific strain in patients with PA. METHODS: Our study included 62 patients with PA (33 aldosterone-producing adenoma [APA] and 29 idiopathic hyperaldosteronism [IHA]) and 30 patients with primary hypertension. STE was acquired using the GE Vivid E9 equipment. The longitudinal (LS) and circumferential (CS) layer-specific strains of the endocardium, midmyocardium, and epicardium (LSendo, LSmid, LSepi, CSendo, CSmid, and CSepi) were obtained using the EchoPAC BT13 workstation. RESULTS: Patients with APA, compared with those with primary hypertension and IHA, had a significantly (P < 0.001) lower serum potassium concentration and plasma renin activity, and higher 24-h urinary aldosterone, plasma aldosterone concentration, and aldosterone-to-renin ratio. Left ventricular ejection fraction was normal in all patients (58-60%). Layer-specific strain showed decreasing gradient from the endocardium to epicardium in all 3 groups (P < 0.01). However, LSendo and CSendo were lowest in APA (-20.2 ± 2.3% and -33.3 ± 3.2%), intermediate in IHA (-22.1 ± 1.9% and -35.7 ± 2.8%) and highest in primary hypertension (-24.1 ± 2.1% and -38.9 ± 3.1%, P < 0.001). Similar trends were observed for LSmid, LSepi, CSmid, and CSepi, but statistical significance was only reached for the comparison between APA and primary hypertension (P < 0.001), but not others (P > 0.05). Layer-specific strain was significantly correlated with plasma aldosterone concentration for all echocardiographic parameters (r = -0.69 to -0.53, P < 0.001) in all 3 groups. CONCLUSIONS: Patients with PA, especially APA, had impaired regional systolic function with myocardial deformation changes at similar levels of blood pressure, probably because of elevated plasma aldosterone concentration.

Echocardiographic strain in hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy.

BACKGROUND: The myocardial structure differs between secondary left ventricular hypertrophy (LVH) and hypertrophic cardiomyopathy (HCM). We investigated left ventricular function of these two types of hypertrophy using multilayer strain analysis with two-dimensional echocardiography. METHODS: Transthoracic echocardiography (Vivid-E9) was performed in 240 patients with preserved left ventricular ejection fraction (LVEF ≥50%) and with either HCM (n = 80, 63 men, age 49.8 ± 14.1 years), hypertensive LVH (n = 80, 63 men, age 51.4 ± 13.3 years) or normal blood pressure and left ventricular structure (n = 80, 63 men, 50.8 ± 12.4 years). Quantitative multilayer longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) were analyzed. The ratio of endo-/epi-myocardial strain was calculated. RESULTS: Longitudinal strain was significantly (P < 0.001) lower in HCM patients than normal controls (15.2 ± 4.2% vs 23.1 ± 2.7%), especially in hypertrophic segments (14.5 ± 4.4% vs 17.2 ± 3.2% in nonhypertrophic segments, P < 0.01). LS was lower in patients with hypertensive LVH, similarly in all left ventricular segments (20.7 ± 3.7%, P < 0.001 vs controls). CS was lower in the mid- and epicardium (P < 0.01), but not endocardium in HCM (P = 0.4), and preserved in all myocardial layers in hypertensive LVH. The endo-/epi-myocardial ratios of both LS and CS were higher in HCM than hypertensive LVH (P < 0.01). RS was higher (P < 0.01) in HCM than hypertensive LVH and controls. Endocardial CS and global RS were correlated with LVEF (r ≥ 0.32, P < 0.01). CONCLUSIONS: Hypertrophic cardiomyopathy patients had marked reductions in LS and CS, whereas patients with hypertensive LVH had less reduction in LS and preserved CS. The increased endo-/epi-myocardial ratios of LS and CS may be useful in differentiating HCM from hypertensive LVH.

Combined use of external therapeutic ultrasound and tirofiban has synergistic therapeutic effects on no-reflow after myocardial reperfusion.

OBJECTIVE: This study aimed to evaluate the effects of the combined use of external therapeutic ultrasound (ETUS) and the specific glycoprotein IIb/IIIa inhibitor tirofiban on myocardial no-reflow in a canine model of acute myocardial infarction after reperfusion. METHODS: The canine myocardial no-reflow model was established by a 3-hour occlusion of the left anterior desecending coronary artery followed by a 2-hour reperfusion. Twenty-four canines were divided into four groups (6/group): (1) control, (2) tirofiban alone, (3) ETUS combined with tirofiban (ETUS + tirofiban), and (4) ETUS alone. RESULTS: The area of no-reflow in each of the three treatment groups was significantly decreased, compared with the control group, with the ETUS + tirofiban group having the smallest area. Also, the ETUS + tirofiban group had the highest recanalized rate of microvessels in the no-reflow area and fewer impaired cellular organelles. The recovery rates of the endocardial and middle circumferential strain as well as longitudinal strain in the ETUS + tirofiban group were significantly greater than those of the tirofiban group. Moreover, the expression of hypoxia-inducible factor-1α (HIF-1α) was significantly increased in the ETUS + tirofiban group, compared with the other groups. CONCLUSIONS: The combined use of ETUS and tirofiban offers synergistic benefits for the treatment of myocardial no-reflow.

New role and molecular mechanism of Gadd45a in hepatic fibrosis.

AIM: To investigate the role of Gadd45a in hepatic fibrosis and the transforming growth factor (TGF)-ß/Smad signaling pathway. METHODS: Wild-type male BALB/c mice were treated with CCl4 to induce a model of chronic liver injury. Hepatic stellate cells (HSCs) were isolated from the liver of BALB/c mice and were treated with small interfering RNAs (siRNAs) targeting Gadd45a or the pcDNA3.1-Gadd45a recombinant plasmid. Cellular α-smooth muscle actin (α-SMA), ß-actin, type I collagen, phospho-Smad2, phospho-Smad3, Smad2, Smad3, and Smad4 were detected by Western blots. The mRNA levels of α-SMA, ß-actin, and type I collagen were determined by quantitative real-time (qRT)-PCR analyses. Reactive oxygen species production was monitored by flow cytometry using 2,7-dichlorodihydrofluorescein diacetate. Gadd45a, Gadd45b, anti-Gadd45g, type I collagen, and SMA local expression in liver tissue were measured by histologic and immunohistochemical analyses. RESULTS: Significant downregulation of Gadd45a, but not Gadd45b or Gadd45g, accompanied by activation of the TGF-ß/Smad signaling pathways was detected in fibrotic liver tissues of mice and isolated HSCs with chronic liver injury induced by CCl4 treatment. Overexpression of Gadd45a reduced the expression of extracellular matrix proteins and α-SMA in HSCs, whereas transient knockdown of Gadd45a with siRNA reversed this process. Gadd45a inhibited the activity of a plasminogen activator inhibitor-1 promoter construct and (CAGA)9 MLP-Luc, an artificial Smad3/4-specific reporter, as well as reduced the phosphorylation and nuclear translocation of Smad3. Gadd45a showed protective effects by scavenging reactive oxygen species and upregulating antioxidant enzymes. CONCLUSION: Gadd45a may counteract hepatic fibrosis by regulating the activation of HSCs via the inhibition of TGF-ß/Smad signaling.

Strategies for classifying patients based on office, home, and ambulatory blood pressure measurement.

Hypertension guidelines propose home or ambulatory blood pressure monitoring as indispensable after office measurement. However, whether preference should be given to home or ambulatory monitoring remains undetermined. In 831 untreated outpatients (mean age, 50.6 years; 49.8% women), we measured office (3 visits), home (7 days), and 24-h ambulatory blood pressures. We applied hypertension guidelines for cross-classification of patients into normotension or white-coat, masked, or sustained hypertension. Based on office and home blood pressures, the prevalence of white-coat, masked, and sustained hypertension was 61 (10.3%), 166 (20.0%), and 162 (19.5%), respectively. Using daytime (from 8 am to 6 pm) instead of home blood pressure confirmed the cross-classification in 575 patients (69.2%), downgraded risk from masked hypertension to normotension (n=24) or from sustained to white-coat hypertension (n=9) in 33 (4.0%), but upgraded risk from normotension to masked hypertension (n=179) or from white-coat to sustained hypertension (n=44) in 223 (26.8%). Analyses based on 24-h ambulatory blood pressure were confirmatory. In adjusted analyses, both the urinary albumin-to-creatinine ratio (+20.6%; confidence interval, 4.4-39.3) and aortic pulse wave velocity (+0.30 m/s; confidence interval, 0.09-0.51) were higher in patients who moved up to a higher risk category. Both indexes of target organ damage and central augmentation index were positively associated (P≤0.048) with the odds of being reclassified. In conclusion, for reliably diagnosing hypertension and starting treatment, office measurement should be followed by ambulatory blood pressure monitoring. Using home instead of ambulatory monitoring misses the high-risk diagnoses of masked or sustained hypertension in over 25% of patients.

Left atrial function as assessed by speckle-tracking echocardiography in hypertension.

We investigated left atrial (LA) function in relation to hypertension using 2-dimensional speckle-tracking echocardiography (STE) in subjects with preserved left ventricular (LV) ejection fraction, while accounting for LA enlargement and LV mass and diastolic function.We performed standard 2-dimensional and Doppler echocardiography and LA volumetric measurements and STE strain imaging in hypertensive patients (systolic/diastolic blood pressure ≥140/90 mmHg, or use of antihypertensive drugs, n = 124) and age- and sex-matched normotensive subjects (n = 124). We measured the peak LA velocity, strain, and strain rate during systole and early and late diastole, respectively. We investigated the associations of interests in the presence or absence of LA enlargement (LA volume index ≥28 mL/m).Hypertensive and normotensive subjects had similar LV ejection fraction and LA diameter (P ≥ 0.22). However, hypertensive compared with normotensive subjects had enlarged LV and impaired diastolic function, and had increased LA volumetric measurements and decreased LA emptying fractions (P < 0.0001). Hypertensive patients also had impaired LA function, as measured by STE velocity, strain, and strain rate in general and in the absence of LA enlargement (P < 0.0001). The differences in LA STE strain rate during LV systole and LA contraction between hypertension and normotension in the absence of LA enlargement remained statistically significant (P < 0.001), after adjustment for age, sex, and LV mass index and E/E'.Hypertension is associated with impaired LA function, as assessed by STE strain imaging technique, even before LA enlargement develops and after LV remodeling is accounted for.