Sex differences in cardiac adaptation to essential hypertension

Left ventricular functional and structural adaptations to mild essential hypertension were assessed by 2D-guided M-mode echocardiography in a population of premenopausal and postmenopausal women (n = 29) who were matched with the same number of men with regard to mean arterial pressure, age and race. Premenopausal women had a thinner posterial wall (P less than 0.05), a smaller left ventricular systolic and diastolic diameter, and a smaller left ventricular mass than men with the same level of arterial pressure. Left ventricular performance indices, ejection fraction, velocity of circumferential fibre shortening, and the ratio of the end-systolic wall stress to the end-systolic volume index (a load-insensitive contractility index) were higher in women than in men. These sex differences were most pronounced before the menopause and tended to disappear thereafter. We conclude that in the presence of the same level of arterial pressure, women have smaller left ventricular dimensions and enhanced ventricular performance compared with men. These differences in cardiac adaptations between the genders may account for the lower risk of cardiovascular morbidity and mortality in premenopausal women with essential hypertension.     

Dimorphic cardiac adaptation to obesity and arterial hypertension

Cardiovascular function and structure were evaluated by M-mode echocardiography and systemic hemodynamics in paired lean and obese patients, either hypertensive or normotensive. Compared to lean patients, obese patients had greater left atrial (p less than 0.0001), ventricular (p less than 0.001), and aortic root (p less than 0.002) diameters; posterior and septal wall thickness (p less than 0.001); and ventricular mass, cardiac output, stroke volume, and stroke work (all p less than 0.0001). Hypertensive patients had increased posterior wall thickness, end diastolic wall stress, stroke work (p less than 0.01), and a lower radius to posterior wall thickness ratio indicating concentric hypertrophy (p less than 0.001) when compared to normotensive patients. Cardiac adaptation to obesity consists of left ventricular dilatation and hypertrophy (eccentric hypertrophy) irrespective of arterial pressure levels. In contrast, essential hypertension solely produces concentric hypertrophy. Both obesity and hypertension increase left ventricular stroke work by disparate hemodynamic mechanisms; their presence in the same patient will tax the heart and increase the long-term risk of congestive failure.     

Echocardiographic and ultrasonographic evaluation of cardiac and vascular hypertrophy in patients with essential hypertension.

High-resolution ultrasonography is a noninvasive technique that allows to investigate the cardiovascular system, in particular the wall thickness and the lumen diameter of the arteries with accuracy and reproducibility. We measured the intima-media thickness of the common carotid artery (CCA) and of its bifurcation (BIF) in 40 patients with essential hypertension, 20 of them with left ventricular hypertrophy (LVH; age 42 +/- 10 years) and 20 without LVH (age 44 +/- 12 years); no other major cardiovascular risk factor was present in all the patients. Both carotid axes have been scanned from different views (anterior, lateral, posterior) on a transversal and longitudinal section using a high-resolution steerable linear array of 5.0 MHz. Carotid diameter and thickness were measured in the longitudinal section. CCA parameters were assessed 20 mm caudally to the flow divider. In patients with LVH, blood pressure (172 +/- 21/108 +/- 9 mm Hg) and left ventricular mass index (156 +/- 38 g/m2) were significantly (p < 0.01) higher than in patients without LVH (blood pressure: 158 +/- 11/99 +/- 12 mm Hg; left ventricular mass index: 98 +/- 10 g/m2), while there was no difference in serum glycemia, triglycerides, total and fractioned cholesterol levels. The intima-media thickness of both the CCA and BIF was significantly higher in the hypertensives with LVH (CCA: 0.85 +/- 0.02 vs. 0.65 +/- 0.02 mm; BIF: 0.93 +/- 0.04 vs. 0.70 +/- 0.03 mm, p < 0.01). There was a statistically significant correlation between the carotid wall thickness and the left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential development of vascular and cardiac hypertrophy in genetic hypertension. Relation to sympathetic function

We compared blood pressure, hindquarter vascular resistance properties, left ventricular weight, and norepinephrine kinetics, in spontaneously hypertensive rats (SHR) and weight-matched normotensive Wistar-Kyoto (WKY) rats at 4, 9, 14, 20, 30, and 50 weeks of age. At 4 weeks, systolic and mean blood pressure measurements were the same in both strains, but the vascular resistance of the fully dilated hindquarter bed was significantly higher in SHR than in WKY rats, with a much larger difference during maximum constriction. Plots of resistance at maximum dilatation and at maximum constriction against body weight suggest that a component of the increase in vascular muscle mass in SHR occurred in the neonatal period preceding hypertension followed by a later component related to the rise in blood pressure. By contrast, left ventricular hypertrophy was minimal at 4 weeks and most of its development paralleled the rise in blood pressure. Sympathetic activity, assessed by norepinephrine fractional rate constant, was higher in SHR than in WKY rats in the left ventricle and kidney through most of the period between 4 and 50 weeks, but was similar in both strains in the muscle bed. This pattern of sympathetic activity will accentuate hypertension once cardiac and vascular hypertrophy are fully established. In all regions, norepinephrine tissue concentration was higher in young SHR and could potentiate the trophic effects of growth factors in early vascular hypertrophy. We suggest that the initial (primary) component of vascular hypertrophy precedes the rise in blood pressure and may be critical in the pathogenesis of hypertension. Possible reasons for the short delay in the rise in blood pressure in young SHR, once the vascular "amplifier" has been established, include high vascularity, immaturity of smooth muscle, and delay in the development of left ventricular hypertrophy.     

Racial differences in cardiac adaptation to essential hypertension determined by echocardiographic indexes

Epidemiologic data point to racial differences in cardiac adaptation to hypertension. In this study, echocardiography and measurement of systemic hemodynamics were performed in 30 black and 30 white patients with untreated essential hypertension. Each black patient was matched with a white patient for age, sex and mean arterial pressure. Wall thickness measurements were similar, but left ventricular mass index was significantly increased in blacks (probability [p] less than 0.05). There was a nonsignificant increase in the number of black patients with posterior wall thickness greater than 1.1 cm. Only in black patients was posterior wall thickness related to systolic (r = 0.45; p = 0.008) and diastolic (r = 0.44; p = 0.0042) pressure and to total peripheral resistance (r = 0.32; p less than 0.046). Thus, although ventricular wall thickness changes are similar in black and white patients, qualitative differences exist in the cardiac adaptive process to systemic hypertension.     

Interrelation of cardiac and vascular structure in young men with borderline hypertension

It is not established whether left ventricular hypertrophy andstructural vascular changes are primary phenomena or secondaryconsequences of raised blood pressure. In this study we investigated54 borderline hypertensive men (BH) (SBP 140–160 mmHgand/or DBP 84–95 mmHg) and 20 normotensive men (NC) (SBP110–130 mmHg and DBP 60–80 mmHg), recruited froman unbiased population sample (age 20 ± 2 years). Bloodpressure (BP) levels were confirmed by i.a. BP recordings. Leftventricular mass (LVM) was determined with M-mode echocardiographyand minimal vascular resistance (R_min) was calculated from theblood flow in the calf and forearm after maximal ischaemic work.Central haemodynamics were assessed by intra-arterial bloodpressure recordings and cardiac output determinations by thedye dilution technique. In the BH group, LVM and R_min were stronglycorrelated to body size, especially weight and body surfacearea. However, LVM and R_min were only weakly correlated to bloodpressure. In the normokinetic BH subgroup (NBH) (n = 38) minimalforearm vascular resistance was significantly higher than inthe hyperkinetic BH individuals (HBH) (n = 16), indicating thepresence of structural vascular changes in the former. Furthermore,in the NBH group there was a significant correlation betweenLVM and R_min both in the calf (r = 0.490 P = 0002) and in theforearm (r = 0.520 P = 0.001). This association remained aftercorrection for body size. No such correlation was seen in theHBH subgroup or in the NC group. The present study does givelong-reaching conclusions as regards the aetiological factorsunderlying the cardiovascular remodelling. However, our datashow that (1) cardiovascular changes appear early in the courseof blood pressure elevation, (2) the cardiac and vascular changesdevelop in parallel, and (3) structural remodelling is not solelyexplained by the degree of blood pressure elevation since bloodpressure was similar in the two BH subgroups. Thus, other factorsthan blood pressure appear to be important determinants of structuraladaptation in mildly hypertensive states.     

Tissue Doppler imaging evaluation of cardiac adaptation to severe pulmonary hypertension

Tissue Doppler imaging (TDI) was used to obtain additional insight into the cardiac adaptation to severe pulmonary arterial hypertension. Pulmonary hemodynamics and right and left ventricular function were investigated in 18 untreated patients, 12 with pulmonary arterial hypertension and 6 with chronic thromboembolic pulmonary hypertension. Fourteen age-matched healthy subjects served as controls for TDI measurements. Pulsed TDI was determined using atrioventricular planes and strain and strain rate along the right ventricular free wall, ventricular septum, and left ventricular lateral wall from 4-chamber apical views. Patients had early diastolic dysfunction, with decreased E-wave peak velocity and increased isovolumic relaxation time, both more important in the right than left ventricle. Compared with controls, strain and strain rate decreased along the right ventricular free wall with a midapical predominance (midbasal strain rate 1.7 +/- 0.6 vs 2.2 +/- 0.5; p = 0.02; midapical strain rate 0.9 +/- 0.9 vs 2.3 +/- 0.7; p <0.001), but were preserved along the left ventricular lateral wall. Tricuspid E-wave and isovolumic relaxation time (R = 0.62, p = 0.006), as well as midapical (r = 0.65, p = 0.004), but not midbasal, right ventricular strain and strain rate correlated with mean pulmonary artery pressures. In conclusion, cardiac function was abnormal in patients with severe pulmonary hypertension because of a combination of alterations in both diastolic and systolic right ventricular function and left ventricular diastolic function. Only right ventricular dysfunction correlated with pulmonary artery pressures.     

Interaction between vascular dysfunction and cardiac mass increases the risk of cardiovascular outcomes in essential hypertension.

AIMS: To investigate the additive prognostic impact of both forearm endothelial dysfunction and left ventricular mass (LVM) for future cardiovascular events. METHODS AND RESULTS: We enrolled 324 Caucasian, never treated, hypertensive outpatients. Endothelial function, by intra-arterial infusion of acetylcholine (ACh), and echocardiographic LVM were investigated. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) and LVM indexed by body surface area (LVMI). Cardiovascular events assessed were: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, transient cerebral ischaemic attack, unstable angina, coronary revascularization procedures, and symptomatic aorto-iliac occlusive disease. During a mean follow-up of 45.2+/-23.6 months, there were 47 new cardiovascular events (3.8 events/100 patient-years). The event rate was 6.8, 2.8, and 1.6% in the tertiles of ACh-stimulated FBF (log-rank test, P=0.0009), and 1.4, 3.4, and 6.6% in the tertiles of LVMI (log-rank test, P=0.0002), respectively. Besides, a significant interaction was documented between FBF and LVMI. In fact, the cardiovascular risk increases up to 11.4% in patients with low FBF and high LVMI. CONCLUSION: For the first time, we demonstrate that the co-existence of LVH and endothelial dysfunction in hypertensive patients increases significantly the risk of subsequent cardiovascular events.     

Ultrasonographic evaluation of cardiac and vascular hypertrophy in patients with essential hypertension]

High resolution ultrasonography allows the accurate and reproducible measurement of thickness and lumen diameter of carotid arteries. We investigated Common carotid (CCA) and bifurcation intima-media thickness in 40 hypertensive patients, 20 without left ventricular hypertrophy (LVH) (age 42 +/- 10 years) and 20 with LVH (age 44 +/- 12 years), all free from other important cardiovascular risk factors. Both carotid axes were scanned from different views (anterior, lateral, posterior) on traversal and longitudinal section, using a high resolution steerable (HRS) 5.0 MHz linear array. Carotid diameter and thickness from longitudinal section were measured. CCA parameters were taken 20 mm caudally to flow divider. Using the B-mode as a guide we assessed LVH presence with M-mode technique when left ventricular mass index (LVMI) > or = 135 g/m2 for men and > or = 110 g/m2 for women. In hypertensive patients with LVH, left ventricular mass was significantly higher than in those without LVH (156 +/- 38 vs 98 +/- 10 g/m2, p < 0.01). Even blood pressure was significantly higher in hypertrophic group (172 +/- 21/108 +/- 9 vs 158 +/- 11/99 +/- 12 mmHg, p < 0.01), while there was no difference in serum glycemia, triglycerides, total and fractioned cholesterol levels. The intima-media thickness scanned in both CCA and bifurcation resulted significantly higher in hypertensives with LVH (CCA: 0.85 +/- 0.02 mm vs 0.65 +/- 0.02 mm; BIF: 0.93 +/- 0.04 mm vs 0.70 +/- 0.03 mm, p < 0.01). We also noticed a statistically significant correlation between carotid wall thickness and left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of early antihypertensive treatment on vascular and cardiac design in SHR with and without renal hypertension.

The present study was designed to explore to what extent pressure reduction by antihypertensive therapy and pressure elevation by renal hypertension are able to affect structural vascular and cardiac changes in young spontaneously hypertensive rats (SHR). Pressure elevation in SHR was induced by means of superimposing 2 kidney, 1 clip renal hypertension (2K1C). Pressure reduction was achieved by means of the vasoselective calcium antagonist felodipine from 6 to 13 weeks of age in both clipped and unclipped SHR. Vascular structure of the skeletal muscle was assessed hemodynamically by perfusing a hindlimb preparation and left ventricular dimensions were calculated from pressure-volume relationships of isolated hearts arrested in diastole. Induction of renal hypertension in SHR resulted, besides augmentation of arterial pressure in a marked concentric left ventricular hypertrophy, i.e. elevations of wall thickness to internal radius ratio. Likewise, in renal hypertensive SHR, a structural adaptation of the skeletal muscle vascular bed occurred, reflected as elevations of minimal vascular resistance and maximal generated perfusion pressure. Antihypertensive treatment for 8 weeks with felodipine reduced and also prevented mean arterial pressure from increasing further in SHR, and in SHR with superimposed renal hypertension by approximately 15% (p < 0.001 for both). In renal hypertensive SHR, felodipine partly prevented the development of exaggerated structural changes, both in the heart and in the skeletal muscle vascular bed, as reflected by reduced wall thickness to internal radius ratio and reduced minimal vascular resistance by 22% and maximal pressure response by 10% respectively (p < 0.01 for both parameters).(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-renin hypertension. Occurrence in vascular complications.

Two hundred one patients with essential hypertension, who had studies of their renin-aldosterone system performed between April 1967 and December 1972, were surveyed for myocardial infraction or cerebrovascular accident. Of the patients, 42% had low plasma renin activity. Myocardial infractions or cerebrovascular accidents were documented in 15% of those with low plasms renin activity and in 5% of those with normal plasma renin activity. When adjustments were made for differences in afe and blood pressure , a protective effect in low-renin hypertension was evident. When black patients were considered separately,there was no difference in diastolic blood pressure; however, vascular complications were not less frequent in low-renin hypertensives. The results suggest that low plasma renin activity does not protect against the development of vascular complications in essential hypertension.     

Pulmonary hypertension in collagen vascular disease.

Pulmonary hypertension is a serious but often overlooked complication in collagen vascular disease. The understanding of the development of pulmonary hypertension has increased substantially during the last years. Abnormal proliferation of pulmonary vascular cells is now being regarded as a predominant process leading to pulmonary vascular obliteration. Medical therapy focuses on prostacyclin treatment, which has been shown to improve exercise capacity and haemodynamic variables in patients with several collagen vascular diseases and pulmonary arterial hypertension. Continuous intravenous prostacyclin remains the standard treatment of associated pulmonary hypertension but less invasive alternatives such as subcutaneous treprostinil, oral beraprost or aerosolized iloprost, as well as, novel substances such as endothelin receptor antagonists may be appropriate for selected patients.     

Development of structural cardiac adaptation in basketball players.

BACKGROUND: As specific features of the basketball player's myocardial structure and function are still rather poorly investigated, we aimed at comparing left ventricular (LV) echocardiographic indices in players of different age groups. METHODS: Male basketball players aged 8-13 years (n=31), 14-17 years (n=31) and 18-28 years (n=31) were examined using standard echocardiography. End-diastolic LV posterior wall thickness and internal diameter, as well as interventricular septum thickness, were measured by M-mode. Relative wall thickness was calculated by dividing the sum of the thicknesses of the interventricular septum and LV posterior wall by LV internal diameter. LV mass and ejection fraction were also calculated. The morphological LV parameters were corrected for body surface area. The peak early (E) and peak late (A) transmitral flow velocities were measured using pulsed Doppler, and the ratio (E/A) was calculated. RESULTS: Significant differences in the absolute internal LV diameter among the age groups disappeared after allometric scaling. However, relative wall thickness as well as body size indexed LV posterior wall thickness and LV mass were significantly greater in the adolescents and adults than in the children. Players of different age groups did not differ in the E/A ratio, while ejection fraction was elevated in adolescents. CONCLUSIONS: Regular basketball training results in moderate cardiac hypertrophy in adolescents and adult athletes due to thickening of myocardial walls.     

Gq signaling in cardiac adaptation and maladaptation

Accumulating evidence suggests that cardiac responses to a number of circulating or locally released humoral factors contribute to adaptive responses after hemodynamic stress or myocardial injury. In particular, hormones such as angiotensin II, endothelin 1, norepinephrine and prostaglandin F2 alpha which bind to and activate cardiomyocyte membrane receptors coupled to the Gq class of GTP binding proteins have been implicated in the development and ultimate decompensation of cardiac hypertrophy. Herein we summarize recent developments in cultured cardiomyocyte and transgenic mouse systems which are defining the phenotypes resulting from Gq signaling events in cardiomyocytes, and which are elucidating the critical downstream mediators. Postulated roles for protein kinase C, p38 MAP kinase and jun-N terminal kinase are discussed in relation to Gq-mediated cardiomyocyte hypertrophy and apoptotic signaling. The evidence to date suggests that molecular targeting of Gq or its effectors has the potential to modify cardiac adaptive and maladaptive responses to stress or injury.