Elevated arterial stiffness and diastolic dysfunction in subclinical hypothyroidism.

BACKGROUND: Thyroid hormone is associated with arterial stiffness and left ventricular diastolic function in hypothyroid disease. The relationship of thyroid hormone level to cardio-ankle vascular index (CAVI) and left ventricular diastolic function, however, remains unclear in subjects with subclinical hypothyroidism. METHODS AND RESULTS: We conducted a cross-sectional study of 83 patients with untreated subclinical hypothyroidism and compared them with 83 randomly selected controls from health check-ups. Log N-terminal prohormone of brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), and arterial stiffness were measured. In addition, we measured early diastolic mitral annular velocity (E') in 43 participants with subclinical hypothyroidism and in 40 controls. When compared with the control group, patients with subclinical hypothyroidism had higher logNT-proBNP (1.9±0.5 vs. 1.7±0.3pg/ml, P<0.05), CRP (0.22±0.04 vs. 0.09±0.06mg/dl, P<0.05), and CAVI (8.8±1.7 vs. 7.8±1.4, P<0.001) and lower E' (5.8±1.7 vs. 7.5±2.1cm/s, P<0.001). CAVI was significantly associated with logNT-proBNP, CRP and E' in the subclinical hypothyroidism group. CONCLUSIONS: High logNT-proBNP was associated with a raised CAVI in patients with subclinical hypothyroidism. Subclinical hypothyroidism may be a risk factor for cardiovascular events related to arterial stiffening and left ventricular diastolic dysfunction.

The impairment of the parasympathetic modulation is involved in the age-related change in mitral E/A ratio.

The mitral early to late diastolic flow velocity ratio (E/A ratio) is age-dependent. It has been considered that its age dependency reflects the age-related lengthening of left ventricular (LV) relaxation; however, the change in E/A ratio is far larger than that expected from those in LV relaxation. We hypothesized that an age-related reduction of the parasympathetic activity increases left atrial (LA) contractility, and that this accounts for the age-related change in E/A ratio. (1) Exercise stress test was performed in 61 normal subjects (age range, 8-80 years, mean, 40 years) to assess heart rate (HR) recovery because slowed HR recovery indicates lowered parasympathetic activity. There were good interrelations among age, E/A ratio, and HR recovery. Among those aged ≤30 years, the age no longer correlated with E/A ratio or HR recovery, but there was a significant correlation between HR recovery and E/A ratio (r = 0.44, p < 0.05). (2) Pulsed Doppler and two-dimensional speckle tracking echocardiography (2DSTE) were performed before and after administration of parasympathetic blockade (atropine) in ten young healthy subjects. LA booster pump function was assessed with LA emptying index calculated by 2DSTE. LA emptying index was calculated from ([LA volume before the atrial contraction - minimal LA volume]/LA volume before the atrial contraction) × 100. Atropine increased mitral A velocity (p < 0.001) and LA emptying index (p < 0.05) along with a decrease in E/A ratio (p < 0.001). Parasympathetic withdrawal enhances LA contraction and increases mitral A velocity, which likely cause a reciprocal decrease in mitral E velocity and E/A ratio. Thus, parasympathetic deactivation with aging should be closely involved in the age-related change in mitral E/A ratio.

Long-term effects of irbesartan on plasma aldosterone concentration and left atrial volume in hypertensive patients.

BACKGROUND: Plasma aldosterone concentration (PAC) is related to cardiac remodeling in patients with hypertension. However, we do not know the detailed relationship between changes in PAC and regression of left atrial (LA) volume following long-term treatment with angiotensin II receptor blocker (ARB) or calcium-channel blocker (CCB). OBJECTIVE: The aim of this study was to investigate the effects of anti-hypertensive monotherapy, an ARB irbesartan or a CCB amlodipine, on PAC and LA reverse remodeling in hypertensive patients. METHODS: A total of 48 patients with untreated hypertension were randomly assigned to irbesartan (ARB group, n=26) and amlodipine (CCB group, n=22). We examined the correlation between LA volume index (LAVI) and other echocardiographic parameters or PAC (n=40) at the baseline and after 12 months of treatment. RESULTS: After 12 months, blood pressure (BP) decreased similarly in both groups. LAVI and PAC significantly decreased in the ARB group, but not in the CCB group (-16±8% vs. 22±9%, p<0.01, -16±9% vs. 11±9%, p<0.05). Larger %-decrease in PAC was associated with larger %-reduction of LAVI in the ARB group (r=0.54, p<0.05), but not in the CCB group. CONCLUSIONS: While BP reduction was similar between the two groups, decrease in LA volume was larger in the ARB group than in the CCB group. Decrease in LA volume was larger in patients with a greater decrease in PAC than in those with smaller decrease in PAC. ARB may facilitate reverse remodeling of LA through decreases in PAC in hypertensive patients.

Role of plasma aldosterone concentration in regression of left-ventricular mass following antihypertensive medication.

BACKGROUND: Aldosterone is known to bring about damage to various organs; however, it is unclear how important the changes in plasma aldosterone concentration (PAC) are as contributors to regression of left-ventricular (LV) mass in hypertensive patients following long-term treatment with calcium channel blockers (CCBs) or angiotensin II receptor blockers (ARBs). OBJECTIVE: To assess the importance of changes in PAC during antihypertensive treatment. METHODS: Forty-four untreated hypertensive patients were randomly assigned to either CCB (amlodipine) group or ARB (losartan) group. In addition to PAC measurements LV geometry was echocardiographically assessed with LV mass index (LVMI) and relative wall thickness (RWT) before and 6 and 12 months after treatment. RESULTS: Reduction of systolic blood pressure (SBP) in 12 months was greater in the CCB group than in the ARB group (-19 ± 8 vs. -11 ± 15%, P < 0.05 as percentage reduction from the values before treatment). PAC decreased in 12 months in the ARB group but not in the CCB group (-31 ± 31 vs. 17 ± 53%, P < 0.01 as percentage reduction from the values before treatment). Larger percentage drop in PAC was associated with larger percentage reduction of LVMI (r = 0.45, P < 0.01 for all). Multiple step-wise regression analysis showed that the percentage reduction of LVMI is related to the percentage changes in SBP and the percentage changes in PAC (r = 0.46, P < 0.01). CONCLUSION: Regression of LV mass was the larger in patients with the greater decrease in PAC associated with antihypertensive medication regardless of CCB or ARB. Changes in PAC and SBP may be key determinants of regression of LV mass in hypertensive patients regardless of the medication selected.

Determinants of plasma brain natriuretic peptide levels in untreated hypertensive patients.

BACKGROUND: Plasma brain natriuretic peptide (BNP) level is elevated in patients with left ventricular (LV) hypertrophy reflecting not only altered LV geometry but LV systolic and/or diastolic dysfunction. However, the values and limitations of BNP measurements are unclear in patients with untreated hypertension. In this study, plasma BNP level was compared with LV geometric and functional characteristics in patients with untreated hypertension. METHODS: Plasma BNP level was measured in 115 patients with untreated hypertension (72 males, 43 females, aged 60 ± 12 years). Routine echo parameters of LV geometry and LV systolic and diastolic performance were also determined. RESULTS: LV ejection fraction was 67 ± 6% and plasma BNP level was 32 ± 30 pg/ml. Plasma BNP levels correlated with age, LV mass index (LVMI), and mitral E velocity, respectively (r = 0.46, p < 0.05; r = 0.21, p < 0.05; r = 0.29, p < 0.05, respectively), but not with systolic blood pressure or relative wall thickness (r = 0.01; r = -0.02). Plasma BNP level correlated with E/E' ratio (r = 0.27, p < 0.05, n = 77). When a stepwise multivariate analysis was performed, E velocity was selected in addition to age and LVMI as significant correlates of plasma BNP level. CONCLUSIONS: LVMI and E velocity were independent determinants of plasma BNP level in patients with untreated hypertension. Plasma BNP level is substantially useful for the screening of abnormalities of LV geometry and/or function in patients with untreated hypertension. Additional echocardiography is useful to assess the mechanism of the elevation of plasma BNP level in untreated hypertensive patients.

Inappropriateness of ventricular hypertrophy is important as a determinant of BNP but not of diastolic filling in untreated hypertensive patients.

Echocardiographically determined inappropriateness of left ventricular mass (LVM) is an independent risk factor for cardiovascular events. Although LV hypertrophy is associated with an increase in the plasma brain natriuretic peptide level and decreased LV diastolic filling, it is unknown whether the inappropriateness of LVM affects them. We studied 77 untreated hypertensive patients (49 men, 28 women, aged 59+/-12 years). The plasma brain natriuretic peptide level was measured, in addition to routine echo Doppler indexes of LV geometry and function. The appropriateness of LVM to cardiac workload was evaluated by the ratio of the observed LVM to the value predicted for individual sex, stroke work and height(2.7) (oLVM/pLVM). Multivariate analysis showed that the plasma brain natriuretic peptide level increased with LVM index but decreased when oLVM/pLVM increased. The ratio of the peak early diastolic flow velocity of mitral flow to the peak early diastolic velocity of mitral annulus (E/E') correlated not only with oLVM/pLVM but also with the LVM index (r=0.30, P<0.05; r=0.37, P<0.05, respectively). However, when a multiple stepwise regression analysis was carried out, only LVM index was determined to be a significant correlate of the E/E' ratio, indicating that the inappropriateness of LVM does not affect the E/E' ratio in hypertensive patients. Brain natriuretic peptide levels are influenced not only by the extent of LV hypertrophy but also by the inappropriateness of hypertrophy in untreated hypertensive patients. Diastolic filling is mostly affected by the extent of LV hypertrophy and not by the appropriateness of hypertrophy.

Value of assessment of left atrial volume and diameter in patients with heart failure but with normal left ventricular ejection fraction and mitral flow velocity pattern.

AIMS: We assessed the comparative value of measurements of tissue Doppler early diastolic mitral annular velocity (E'), left atrial diameter (LAD), and left atrial volume (LAV) in patients with possible heart failure (HF) but with normal left ventricular (LV) ejection fraction (EF) and mitral flow velocity pattern. METHODS AND RESULTS: We determined LAV and LAD indexes in addition to the ratio of peak early diastolic mitral flow velocity (E) to E' (E/E' ratio) in 91 patients with all three of the followings: HF, LVEF of greater than 55%, and normal mitral E/A ratio between 0.8 and 1.5. Twenty healthy subjects were used as controls. E/E' ratio was abnormal (>1.5) in 38 of the 91 patients (sensitivity=44%). LAV index was 32 mL/m(2) or greater in 71 of the 91 patients (sensitivity=78%), while LAD index was 27 mm/m(2) or greater in 81 of 91 patients (sensitivity=89%). The area under the curve by receiver-operator curve analyses was 0.995 for LA volume index, 0.998 for LAD index, and 0.885 for E/E' ratio. CONCLUSION: LAV and LAD indexes are more useful in detecting with HF and normal EF patients than E' related parameters.

Characterization of left ventricular filling abnormalities and its relation to elevated plasma brain natriuretic peptide level in acute to chronic diastolic heart failure.

BACKGROUND: Although Doppler left ventricular (LV) filling abnormalities have been extensively analyzed in patients with systolic heart failure (SHF), they have not yet been well characterized in patients with acute to chronic diastolic heart failure (DHF) in the light of plasma brain natriuretic peptide (BNP) levels. METHODS AND RESULTS: In 25 patients presenting with acute DHF and 25 with acute SHF, echo Doppler parameters and plasma BNP levels were obtained on admission and in the chronic stage. The mitral E/A ratio was lower in DHF patients than in SHF patients in the acute stage (1.3 +/-0.4 vs 1.8+/-0.9, p<0.05), and in the chronic stage of DHF the ratio decreased with plasma BNP level, but plasma BNP level was still greater than 100 pg/ml in 15 patients (60%). Among patients with DHF the plasma BNP level did not correlate with the mitral E/A ratio or deceleration time (r=0,25, p=NS; r=0,23, p=NS), but did with estimated pulmonary artery systolic pressure (r=0.64, p<0.01). CONCLUSIONS: A restrictive mitral flow velocity pattern is observed in only 25% of patients with DHF, so it is particularly important to recognize pseudonormalization in those with possible DHF. Persistently elevated plasma BNP level is not primarily caused by LV diastolic dysfunction, but by secondary alteration for hemodynamic adjustment (elevated LV end-diastolic pressure) in patients with DHF.