Three-dimensional echocardiographic evaluation of the right ventricle in patients with uncomplicated systemic lupus erythematosus.

Our aim was to identify subclinical right ventricular (RV) alterations in systemic lupus erythematosus (SLE) by combining standard and three-dimensional echocardiography (3DE). Fifty SLE patients without concomitant cardiac disease and 50 healthy controls, matched for age and gender, were enrolled. Disease damage was evaluated by inflammatory markers and SLE damage index. All patients underwent an echo-Doppler examination with 3DE assessment of RV function, RV septal and lateral longitudinal strain. The two groups had comparable body mass index and blood pressure. RV transversal middle diameter and pulmonary arterial pressure were significantly higher in SLE compared to controls. By 3DE, RV end-systolic volume ( p = 0.037) was greater, whereas stroke volume ( p = 0.023), ejection fraction ( p < 0.0001) and septal and lateral longitudinal strain (both p < 0.0001) were lower in SLE. SLE damage index ≥ 1 was negatively associated with tricuspid annular plane systolic excursion (TAPSE) ( p < 0.002), tricuspid E/A ratio ( p = 0.003), RV ejection fraction ( p < 0.05), lateral longitudinal strain ( p < 0.0001) and septal longitudinal strain ( p = 0.04). By separate multivariate models, after adjusting for age, C reactive protein and proBNP, SLE damage index was independently associated with TAPSE ( p = 0.009) and RV lateral longitudinal strain ( p = 0.007). In conclusion, a subclinical RV systolic dysfunction is detectable in SLE by 3DE, RV lateral wall strain being a key parameter. RV dysfunction is associated with cumulative disease damage.

Identification of phenotypes at risk of transition from diastolic hypertension to isolated systolic hypertension.

Little is known about the potential progression of hypertensive patients towards isolated systolic hypertension (ISH) and about the phenotypes associated with the development of this condition. Aim of this study was to detect predictors of evolution towards ISH in patients with initial systolic-diastolic hypertension. We selected 7801 hypertensive patients free of prevalent cardiovascular (CV) diseases or severe chronic kidney disease and with at least 6-month follow-up from the Campania Salute Network. During 55±44 months of follow-up, incidence of ISH was 21%. Patients with ISH at the follow-up were significantly older (P<0.0001), had longer duration of hypertension, higher prevalence of diabetes and were more likely to be women (all P<0.0001). They exhibited higher baseline left ventricular mass index (LVMi), arterial stiffness (pulse pressure/stroke index), relative wall thickness (RWT) and carotid intima-media thickness (IMT; all P<0.001). Independent predictors of incident ISH were older age (odds ratio (OR)=1.14/5 years), female gender (OR=1.30), higher baseline systolic blood pressure (OR=1.03/5 mm Hg), lower diastolic blood pressure (OR=0.89/5 mm Hg), longer duration of hypertension (OR=1.08/5 months), higher LVMi (OR=1.02/5 g m(-2.7)), arterial stiffness (OR=2.01), RWT (OR=1.02), IMT (OR=1.19 mm(-1); all P<0.0001), independently of antihypertensive treatment, obesity, diabetes and fasting glucose (P>0.05). Our findings suggest that ISH is a sign of aggravation of the atherosclerotic disease already evident by the target organ damage. Great efforts should be paid to prevent this evolution and prompt aggressive therapy for arterial hypertension should be issued before the onset of target organ damage, to reduce global CV risk.

Mitral annular longitudinal function preservation after mitral valve repair: the MARTE study.

BACKGROUND: In patients with chronic mitral regurgitation (MR), undergoing surgical mitral valve repair, current Guidelines only recommend standard echocardiographic indices i.e. left ventricular (LV) ejection fraction (EF), and LV end-systolic and end-diastolic diameters as preoperative variables. However LV EF is often preserved until advanced stages of the valve disease. Aim of this study was to evaluate changes in LV systolic longitudinal function, 3 months after mitral valve repair in patients with chronic degenerative MR and normal preoperative EF. METHODS: We measured M-mode mitral lateral annulus systolic excursion (MAPSE) and Tissue Doppler (TD) peak systolic annular velocity (S(m)) in 31 patients with moderate to severe MR and normal EF (59.9 ± 4.7%) candidates for mitral valve repair, preoperatively and 3 months after surgery. RESULTS: After mitral valve repair, S(m) increased from 7.8 ± 1.4 to 9.6 ± 2.2 cm/s (p<0.0001) and MAPSE increased from 1.33 ± 0.26 to 1.55 ± 0.25 cm (p=0.0013). EF decreased from 59.9 ± 4.7 to 51.3 ± 5.9% (p<0.0001). As expected, LV diameters and volumes, wall thicknesses, midwall fractional shortening (mFS), and left atrial (LA) size were all reduced after surgery. CONCLUSIONS: This study suggests that assessment of LV long axis systolic velocity and amplitude of excursion by echocardiography is more sensitive than simple determination of EF for revealing the beneficial impact of MR surgery on overall systolic function.

Coronary vasoreactivity is not altered in young people with type 1 diabetes.

BACKGROUND AND AIM: Abnormal coronary microvascular circulation has been demonstrated in diabetes and is associated with increased rate of cardiovascular events. Our objective was to evaluate coronary vasoreactivity in young people with type 1 diabetes with and without microvascular complications. METHODS AND RESULTS: Twenty-five type 1 diabetic patients without microvascular complications (DC-), 23 with microvascular complications (DC+), and 18 control subjects (C) were studied. Coronary vasoreactivity was assessed by means of coronary flow reserve (CFR). Blood flow velocity in the left anterior descending coronary artery was measured at rest and after high-dose dipyridamole using transthoracic color-guided pulsed Doppler echocardiography. CFR was defined as the ratio of hyperaemic to resting diastolic peak flow velocities. The three groups had similar cardiac function parameters, and also systolic and diastolic blood pressure at rest, which remained unchanged during dipyridamole infusion. Resting coronary flow velocity was comparable in C, DC-, and DC+ (p=ns). Dipyridamole infusion produced a threefold increase in coronary diastolic peak velocity, which reached similar values in C (0.69±0.16 m/s), DC- (0.69±0.18 m/s), and DC+ (0.66±0.11 m/s). Mean CFR ratio was similar in C (3.33±0.66), DC- (3.30±0.51), and DC+ (3.24±0.60). At multiple linear regression analysis, no association was found between CFR and age, sex, HbA(1c), duration of diabetes, and complications. CONCLUSION: Coronary vasodilatory function is preserved in young D patients, even those with early microvascular complications, suggesting that coronary vasoreactivity deteriorates at more advanced stages of microvascular complications and/or in the presence of other cardiovascular risk factors.

Triphasic diastolic pattern and delayed timing of myocardial relaxation identify dynamic changes of left ventricular filling pressure.

The case reported concerns a woman with hypertensive emergency, showing triphasic diastolic pattern with mid-diastolic velocity both at transmitral inflow and at pulsed tissue Doppler-derived septal/lateral mitral annulus. In addition, the time from EKG R wave peak to annular early diastolic velocity (Em) onset was longer than the time occurring between R peak and transmitral E velocity. E/Em ratio was 14.6 and left atrium enlarged. After blood pressure fall and clinical stabilization, the triphasic diastolic patterns were again observed. However, the timing of early diastolic velocity was the same at mitral inflow and annular tissue Doppler. E/Em ratio and left atrial volume were reduced. The present report highlights the additional value of pulsed tissue Doppler to detect alteration of diastolic properties and dynamic changes of left ventricular filling pressure.

Negative stress echo: further prognostic stratification with assessment of pressure-volume relation.

BACKGROUND: A maximal negative stress echo identifies a low risk for subsequent hard events subset. However, the potentially prognostically relevant information on global contractile reserve on the left ventricle is missed by standard regional wall motion assessment, and can be obtained by end-systolic pressure-volume relationship (PVR) evaluation. AIM: To assess the relative prognostic value of PVR in patients with negative stress echo. METHODS: We enrolled 99 consecutive patients (age=61+/-14 years; 81 males, LVEF 47+/-14%, WMSI=1.42+/-0.50) with negative exercise stress echo for standard wall motion criteria. To build the PVR, the force was determined at rest and peak stress as the ratio of the systolic pressure/end-systolic volume index. All patients were followed-up on medical therapy. RESULTS: Median follow-up was 21 months (interquartile range 12-26). Twenty-nine events have been observed: 6 deaths, 10 heart failure related hospitalization and 13 worsening NYHA class of >or=1 grade. Using Cox's proportional hazard model the best independent predictor of total events was SP/ESV index change (rest-stress) <1.5 mm Hg/ml/m(2) as determined by ROC analysis cut-off (RR=29, p=0.001, sensitivity=80%, specificity=93%). The overall survival and event-free survival was 34% in patients with change (rest-stress) SP/ESV index<1.5 mm Hg/ml/m(2) and 97% in whose with >1.5 mm Hg/ml/m(2). CONCLUSIONS: In patients with negative stress echo, a preserved global contractility response can be easily identified through stress-induced variation in SP/ESV index, with powerful further risk stratification.

Transthoracic echo-Doppler assessment of coronary microvascular function late after Kawasaki disease.

The goal of this study was to demonstrate that Doppler transthoracic echocardiography (TTE) may represent a valuable tool for the noninvasive demonstration of coronary microvascular dysfunction in children with previous Kawasaki disease (KD) by the measurement of coronary flow reserve (CFR) during cold pressor test (CPT). Twenty-five children with previous KD (mean follow-up, 4.6 +/- 2.6 years) were included in the study-16 with no evidence of coronary artery lesions (CALs(-)) by TTE and 9 with coronary aneurysms (CALs(+)). Seventeen age-matched healthy subjects were also recruited. Diastolic peak velocity was measured by pulsed Doppler both at rest (DPV(Rest)) and during CPT (DPV(CPT)) in the anterior descending artery. CFR was calculated as DPV(CPT)/DPV(Rest). KD patients demonstrated significantly higher values of DPV(Rest) (0.21 +/- 0.05 vs 0.13 +/- 0.01 cm/sec, p < 0.0001) and DPV(CPT) (0.33 +/- 0.07 vs 0.27 +/- 0.03 cm/sec, p < 0.005). CFR was reduced in KD compared to control subjects (1.5 +/- 0.4 vs 2.1 +/- 0.2, p < 0.0001). CFR was decreased in a similar manner in both CALs(+) patients (1.4 +/- 0.4, p = 0.002 vs controls) and CALs(-) patients (1.6 +/- 0.4, p < 0.0001 vs controls). Doppler TTE at rest and during CPT may represent a valuable modality for CFR evaluation in children with a history of KD. CFR is significantly reduced in KD patients independently of the presence of CALs.

A retrospective analysis on biochemical parameters, cardiovascular risk and cardiomyopathy in elderly acromegalic patients.

This analytical, observational, retrospective, case-control study was designed to describe clinical presentation, biochemical disease severity, presence, and severity of metabolic and cardiovascular complications in patients diagnosed as having acromegaly at 60 yr or older (no.=57) as compared to sex- and age-matched healthy controls. Patients and controls underwent a complete endocrine, metabolic, and cardiovascular check-up. The age at diagnosis was equally distributed between 60 to 75 yr while only a minority of the patients (5.3%) was diagnosed after 75 yr. Median GH and IGF-I levels were 15 microg/l and 557 microg/l. The prevalence of microadenomas, enclosed macroadenomas, and extrasellar/invasive macroadenomas was 30%, 49%, and 21%, respectively. All patients had joint complaints and goiter (euthyroid in 65% and pre-toxic/toxic in 35%), 82% had hypertension, 58% diabetes and 54% had both. As compared to controls, a higher number of patients were receiving treatment with anti-arrhythmiacs (p=0.033), anti-aggregants (p=0.013), levothyroxine (p=0.015), and metformin (p=0.022). Nevertheless, the patients had higher systolic and diastolic blood pressure, heart rate, left ventricular mass index, lipids, glucose and insulin levels as well as percent function of beta cells than controls. In conclusion, the high prevalence of systemic complications makes elderly acromegalics more susceptible than controls to cardiovascular events. We suggest that an accurate clinical check-up and, possibly, a more aggressive treatment of hypertension and diabetes are required in elderly acromegalics.

Role of regional mechanical dyssynchrony as a determinant of functional mitral regurgitation in patients with left ventricular systolic dysfunction.

OBJECTIVE: To assess regional mechanical dyssynchrony as a determinant of the degree of functional mitral regurgitation (FMR). SETTING: Tertiary cardiology clinic. PATIENTS: 74 consecutive patients with left ventricular (LV) dysfunction (ejection fraction < 40%, mean 32.2 (SD 7.3)%) were evaluated. METHODS: Effective regurgitant orifice (ERO) area, indices of mitral deformation (systolic valvular tenting, mitral annular contraction) and of global LV function and remodelling (ejection fraction, end systolic volume, sphericity index) and local remodelling (papillary-fibrosa distance, regional wall motion score index), and tissue Doppler-derived dyssynchrony index (DI) (regional DI, defined as the standard deviation of time to peak myocardial systolic contraction of eight LV segments supporting the papillary muscles attachment) were measured. RESULTS: All the assessed variables correlated significantly with ERO. By multivariate analysis, systolic valvular tenting was the strongest independent predictor of ERO (R(2) = 0.77, p = 0.0001), with a minor influence of papillary-fibrosa distance (R(2) = 0.77, p = 0.01) and regional DI (R(2) = 0.77, p = 0.03). Local LV remodelling (regional wall motion score index: R(2) = 0.58, p = 0.001; papillary-fibrosa distance: R(2) = 0.58, p = 0.002) and global remodelling indices (sphericity index: R(2) = 0.58, p = 0.003) were the main determinants of systolic valvular tenting, whereas regional DI did not enter into the model. Regional DI was an independent predictor of ERO (R(2) = 0.56, p = 0.005) in patients with non-ischaemic LV dysfunction but not in patients with ischaemic LV dysfunction when these groups were analysed separately. CONCLUSIONS: The degree of FMR is associated mainly with mitral deformation indices. The regional dyssynchrony also has an independent association with ERO but with a minor influence; however, it is not a determinant of FMR in patients with ischaemic LV dysfunction.

Pulsed tissue Doppler imaging detects early myocardial dysfunction in asymptomatic patients with severe mitral regurgitation.

OBJECTIVE: To assess whether tissue Doppler myocardial imaging (TDI) indices can predict postoperative left ventricular function in patients with mitral regurgitation (MR) after surgical correction. METHODS: 84 patients (mean (SD) age 54.3 (10.8) years) with asymptomatic severe MR, an end systolic diameter < 45 mm, and an ejection fraction (EF) > 60% were subdivided in two groups: 43 patients with a postoperative EF reduction < 10% (group 1) and 41 patients with a postoperative EF reduction > or = 10% (group 2).TDI systolic indices of the lateral annulus were analysed preoperatively to assess myocardial systolic wave (Sm) velocity, myocardial precontraction time (PCTm), myocardial contraction time (CTm), and the PCTm:CTm ratio. RESULTS: Postoperative EF decreased significantly (from 67 (5)% to 60 (5.5)%, p = 0.0001). Group 2 had a higher PCTm, CTm, and PCTm:CTm ratio and a lower Sm velocity than group 1 (PCTm 100.4 (19) ms v 82 (21.8) ms, p = 0.004; CTm 222 (3.1) ms v 215 (2.3) ms, p = 0.01; PCTm:CTm 0.45 (0.08) v 0.38 (0.09), p = 0.001; Sm velocity 10.4 (1.1) cm/s v 13 (1.3) cm/s, p = 0.0001). Multivariate regression analysis showed that the combination of PCTm:CTm ratio > or = 40 ms and Sm velocity < or = 10.5 cm/s was the main independent predictor of postoperative EF reduction > or = 10% (sensitivity 78%, specificity 95%). CONCLUSIONS: TDI systolic indices can predict postoperative left ventricular function in patients with asymptomatic MR undergoing surgical correction.

Right ventricular diastolic dysfunction in arterial systemic hypertension: analysis by pulsed tissue Doppler.

AIMS: This study analyses right ventricular longitudinal function in arterial systemic hypertension by pulsed tissue Doppler. METHODS AND RESULTS: Thirty normotensives and 30 hypertensives, free of cardiac drugs, underwent standard Doppler echocardiography and pulsed tissue Doppler of right ventricular lateral tricuspid annulus and left ventricular lateral mitral annulus. By tissue Doppler, systolic and diastolic measurements were obtained. Hypertensives had higher left ventricular mass and impaired Doppler diastolic indexes, without changes of global systolic function. Tissue Doppler showed reduction of right ventricular E/A ratio and prolongation of relaxation time in comparison with controls (both P<0.00001). In the overall population, the length of tissue Doppler derived right ventricular relaxation time was positively related to right ventricular anterior wall thickness while right ventricular E/A ratio was positively related to E/A ratio of left ventricular mitral annulus (both P<0.00001). These relations remained significant even after adjusting for clinical and echocardiographic confounders by separate multivariate models. CONCLUSIONS: Arterial systemic hypertension is associated to right ventricular longitudinal diastolic dysfunction. This dysfunction involves the prolongation of active relaxation, which is independently associated with the degree of right ventricular hypertrophy and the impairment of passive wall properties, which is mainly due to ventricular interaction occurring under left ventricular pressure overload conditions.

Usefulness of Doppler tissue imaging for the assessment of right and left ventricular myocardial function in patients with dual-chamber pacing.

The aim of the study was to evaluate by Doppler tissue imaging (DTI) the combined effects of atrio-ventricular (AV) delay and heart rate (HR) changes on global and segmental right (RV) and left (LV) ventricular diastolic function in 15 patients with dual-chamber pacemakers paced in the DDD mode. RV and LV inflow velocities and regional systolic and diastolic pulsed-wave (PW) DTI parameters were analyzed at four different pacing modes: (1) HR 70 beats/min, AV delay 125 ms; (2) HR 70 beats/min, AV delay 188 ms; (3) HR 89 beats/min, AV delay 125 ms; (4) HR 89 beats/min, AV delay 188 ms. For each pacing mode selected, RV diastolic filling velocities always prevailed over LV ones. As for RV and LV adaptation to the four different stimulation protocols, a higher paced rate and a prolonged AV delay caused across both the AV valves a decrease of E wave and of E/A ratios. The intersegmental comparison of PW-DTI parameters outlined that RV free wall exhibited significantly higher peak systolic (Sm) and early-diastolic (Em) wall velocities, and longer systolic ejection time. Considering separately RV and LV segmental physiology at the four programmed pacing modes, an increase in HR determined a progressive shortening of systolic ejection times in all the segments analyzed. Moreover, in each region the Em/Am ratio decreased with higher HR and longer AV delay. Conversely, Em encountered a progressive reduction in RV free wall, while remaining quite unchanged in all the LV regions. Both ventricles shared a similar pattern of global and regional adaptation to programmed HR and AV delay modifications, consisting in a progressive greater contribution of late diastole to ventricular filling at higher HR and more prolonged AV delay. However, at a regional level the right ventricle exhibited higher systolic and diastolic wall velocities than all left ventricular regions.

Independent association of plasma leptin levels and left ventricular isovolumic relaxation in uncomplicated hypertension.

BACKGROUND: On the basis of evidence of plasma leptin (LE) effects on cardiovascular system, we assessed possible association of LE and Doppler-derived left ventricular (LV) diastolic function in arterial hypertension. METHODS: Doppler echocardiography, blood sample for fasting plasma LE levels, and euglycemic hyperinsulinemic glucose clamp were performed on 15 healthy insulin-sensitive men and 40 newly diagnosed hypertensive men, who were divided into two groups according to insulin sensitivity degree: 15 insulin sensitive (IS) and 25 insulin resistant (IR) individuals (whole body glucose disposal >33.3 and <33.3 micromol/kg, respectively). RESULTS: The IR hypertensives had significantly higher body mass index (BMI), waist/hip ratio, LE and LV mass index than the other two groups. IR hypertensives had lower LE (even after adjusting for BMI and waist/hip ratio) and among LV diastolic indexes, lower E peak velocity (P < .05) and longer isovolumic relaxation time (IVRT) (P < .001) in comparison to IR hypertensives. IR hypertensives had the lowest E/A ratio (0.88 +/- 0.2) compared to IS patients (1.03 +/- 0.1 P < .05) and controls (1.31 +/- 10.2 P < .001). By multiple linear regression analyses performed both in the overall population and hypertensives, LV mass index and LE were independently associated to IVRT (R2 = 0.41 in overall population, R2 = 0.42 in hypertensives, both P < .0001), whereas age, heart rate, diastolic and systolic blood pressure (BP), BMI, waist/hip ratio, and insulin action were not significant. CONCLUSIONS: Our study underscores an independent association of increased plasma LE and lengthening of isovolumic relaxation in uncomplicated hypertension. Further studies will need to understand the conditions underlying both these phenomena.

Association between myocardial right ventricular relaxation time and pulmonary arterial pressure in chronic obstructive lung disease: analysis by pulsed Doppler tissue imaging.

This study assessed right ventricular function in chronic obstructive lung disease and pulmonary hypertension by Doppler tissue imaging. Doppler echocardiography of the right ventricle and Doppler tissue imaging of the tricuspid annulus were performed in 63 subjects: 20 healthy controls, 20 with lung disease, and 23 with both lung disease and pulmonary hypertension. Two-dimensional tricuspid systolic plane excursion was lower in patients with pulmonary hypertension than in the other 2 groups. Doppler tricuspid inflow measurements distinguished patients in both of the diseased groups from the control subjects, but they did not differentiate patients with pulmonary hypertension from those without it. The ratio of peak E-wave to peak A-wave velocities derived by Doppler tissue imaging was significantly lower and the myocardial acceleration time longer in both groups of lung disease than in the control group. Only myocardial relaxation time distinguished the 3 groups (all P <.01); a gradual increase in time occurred, with the shortest time seen in controls, a longer time in patients with chronic obstructive lung disease without pulmonary hypertension, and the longest time in patients with lung disease and pulmonary hypertension. In the overall population including subjects with at least minimal tricuspid regurgitation, myocardial relaxation time was positively related to pulmonary systolic pressure. In conclusion, Doppler tissue imaging distinguishes subsets of patients affected by lung disease with or without pulmonary hypertension and identifies patients with different levels of pulmonary artery systolic pressure.

Left ventricular systolic and diastolic function after anthracycline chemotherapy in childhood.

BACKGROUND: In childhood, late cardiotoxicity is characterized by inappropriately thin wall and consequent increased end-systolic wall stress, but the associations of impaired left ventricular geometry and function occurring under these circumstances need further investigation. HYPOTHESIS: The purpose of this study was to assess anthracycline late effects on the relationships occurring between increased end-systolic stress (ESS) and changes in both M-mode systolic measurements (i.e., endocardial and midwall fractional shortening) and Doppler diastolic indices in the pediatric age. METHODS: The population consisted of 101 children treated with anthracyclines for at least 12 months and 91 healthy children. Using M-mode echocardiography, end-systolic wall stress was calculated as index of afterload, and endocardial and midwall fractional shortening as systolic indices. Doppler transmitral measurements were made as diastolic indices. RESULTS: Patients treated with anthracyclines showed significantly lower relative wall thickness and left ventricular mass index, greater end-systolic wall stress, reduced endocardial and midwall fractional shortening and peak E/A ratio, prolonged deceleration, and isovolumic relaxation times. Direct relationships were found between end-systolic wall stress and both endocardial and midwall shortening. The use of midwall shortening in the relation showed a greater, but not significant increase (from 3 to 6%) in the proportion of patients with depressed systolic function than did endocardial shortening. In the anthracycline group, end-systolic wall stress was also inversely related to relative wall thickness and directly to isovolumic relaxation time. CONCLUSIONS: In childhood, reduced myocardial thickness and increased afterload explain much of systolic and diastolic dysfunction of late anthracycline toxicity. Midwall fractional shortening does not seem to add useful information for identifying subsets of children more prone to the development of heart failure.

Inverse association between free insulin-like growth factor-1 and isovolumic relaxation in arterial systemic hypertension.

Several trials have suggested that insulin-like growth factor-1 (IGF-1) may have a pathophysiological role in the development of arterial essential hypertension. To verify the possible association of IGF-1 with left ventricular morphological and functional echocardiographic parameters in hypertension, we studied 40 male patients with newly diagnosed hypertension and 15 normotensive control subjects. Doppler echocardiography was performed and circulating free IGF-1 levels were determined in all subjects. Circulating free IGF-1 levels were higher in hypertensives than in control subjects (P<0.01). A significant inverse correlation was observed between free IGF-1 and isovolumic relaxation time in the overall population (r=-0.37, P<0.01) and in hypertensives (r=-0.57, P<0.0001), whereas this relation disappears in normotensives. These results were confirmed by multivariate analysis. The present study confirms that arterial essential hypertension represents a clinical condition associated with an increased synthesis of IGF-1. The observation of an inverse, independent association between free IGF-1 and isovolumic relaxation time suggests 2 alternative hypotheses: a possible beneficial effect of IGF-1 to diastolic relaxation or a resistance to IGF-1 in hypertension.