Does information on systolic and diastolic function improve prediction of a cardiovascular event by left ventricular hypertrophy in arterial hypertension?

Left ventricular (LV) mass (LVM) is the most important information requested in hypertensive patients referred for echocardiography. However, LV function also predicts cardiovascular (CV) risk independent of LVM. There is no evidence that addition of LV function significantly improves model prediction of CV risk compared with LVM alone. Thus, composite fatal and nonfatal CV or cerebrovascular events were evaluated in 5380 hypertensive outpatients (2336 women, 298 diabetics, and 1315 obese subjects) without prevalent CV disease (follow-up: 3.5+/-2.8 years). We compared 5 risk models using Cox regression and adjusting for age and sex: (1) LV mass normalized for height in meters(2.7) (LVMi); (2) LVMi, concentric LV geometry, by relative wall thickness (>0.43), ejection fraction, and transmitral diastolic pattern (by thirtiles of mitral deceleration index); (3) LVMi, LV geometry, midwall shortening, and mitral deceleration index thirtiles; (4) as No. 2 with the addition of left atrial dilatation (>23 mm); and (5) as No. 3 with the addition of left atrial dilatation. Individual hazard functions were compared using receiving operating characteristic curves and z statistics. Areas under the curves increased from 0.60 in the model with the sole LVMi to 0.62 in the others (all P values for differences were not significant). The additional information on systolic and diastolic function decreased the contribution (Wald statistics) of LVMi in the Cox model without improving the model ability to predict CV risk. We conclude that risk models with inclusion of information on LV geometry and systolic and diastolic function, in addition to LVMi, do not improve the prediction of CV events but rather redistribute the impact of individual predictors within the risk variance.

[Usefulness of a telematic system and image analysis in the follow-up of high-risk patients: a new health service model]. / L'approccio telematico nella riduzione del rischio cardiovascolare: un nuovo modello organizzativo assistenziale.

BACKGROUND: Inadequate blood pressure control in hypertensive patients is in contrast with the evidence from clinical studies of effectiveness of the same antihypertensive compounds used in clinical practice. These results may be due to follow-up management of hypertensive patients and in particular to the interaction between general practitioners (GPs) and hypertension specialists. The aim of this study was to assess the effectiveness of an internet-based digital network, connecting specialists and GPs in the Campania Region, on blood pressure control and major cardiovascular events. METHODS: A network between the Hypertension Center of "Federico II" University, 14 specialist centers and 60 GPs was done in the Campania Region (Campania Salute Project, CS). Randomized GPs enrolled in CS could update online clinic records of patients (n = 1979). As a control group, we included 2045 patients referred to the specialist centers by GPs from outside the network. All patients completed a 2-year follow-up. RESULTS: CS determined a significant reduction in systolic and diastolic blood pressure (CS group 144 +/- 18/91 +/- 11 vs 136 +/- 17/86 +/- 10 mmHg; control group 144 +/- 17/90 +/- 10 vs 139 +/- 15/87 +/- 9 mmHg, p < 0.001). Indeed, the CS group showed less frequent fatal and non-fatal major cardiovascular events (2.9 vs 4.3%, chi2 = 5.047, p < 0.02). CONCLUSIONS: Our results support the hypothesis that telematic connections may contribute to improve blood pressure control and reduce major cardiovascular events.

Beta2-adrenergic receptor polymorphisms and treatment-induced regression of left ventricular hypertrophy in hypertension.

OBJECTIVES: Although blood pressure is considered the major determinant of left ventricular hypertrophy in hypertension, genetic variability is increasingly being considered among the factors influencing this complication. beta(2)-Adrenergic receptors (beta(2)ARs) are up-regulated in hypertension and largely polymorphic within the human population. Recently, we have shown that the Glu27 beta(2)AR variant is strongly associated with cardiac hypertrophy in hypertension. The objective of this study is to verify whether this polymorphism also affects hypertrophy regression in response to antihypertensive therapy. METHODS: In a prospective follow-up study we screened 970 hypertensive patients of Caucasian descent for the Gly16Arg, Gln27Glu, and Thr164Ile beta(2)AR polymorphisms and left ventricular echocardiographic hypertrophy and assigned selected patients to enalapril or atenolol to assess left ventricular hypertrophy regression after 2-year follow-up. Results were stratified according to treatment and the Glu27Gln polymorphism of the beta(2)AR. In cells with stable overexpression of the Glu27 or Gln27 variant of beta(2)AR, we also explored the implications of this polymorphism on hypertrophy-related intracellular signal transduction. RESULTS: Among hypertensive patients, the Gly16 allele was found in 63% of patients and the Glu27 allele was found in 40.6%. Both polymorphisms were in linkage disequilibrium, as expected. Four hundred forty-one hypertrophic hypertensive patients completed the 2-year follow-up. At baseline, patients carrying at least 1 allele of the Glu27 variant presented with a larger cardiac size despite similar blood pressure levels (142.9 +/- 22.5 g/m(2) in Glu27 carriers versus 138.2 +/- 18.4 g/m(2) in Gln27 carriers, P < .02). Blood pressure normalization was achieved by both drugs. At follow-up, compared with the Gln27 patients, the Glu27 patients showed a larger reduction in hypertrophy when treated with enalapril (percent change in left ventricular mass, -6.3% +/- 7.7% in Glu27 carriers versus -2.18% +/- 7.9% in Gln27 carriers; P < .05) but not with atenolol therapy (-2.8% +/- 8.9% in Glu27 carriers versus -2.4% +/- 8.8% in Gln27 carriers, P = not significant). In in vitro studies the activation of p38 and extracellular signal-regulated kinase (ERK-) 1/2 (data not shown) and the activity of the atrial natriuretic factor (ANF) promoter after isoproterenol (INN, isoprenaline) stimulation were larger in Glu27 beta(2)AR overexpressing cells than in Gln27 beta(2)AR overexpressing cells (fold difference compared with unstimulated cells, 9.7 +/- 2.9 for Glu27 beta(2)AR versus 4.2 +/- 0.3 for Gln27 beta(2)AR; P < .05). CONCLUSIONS: The Glu27 variant of beta(2)AR enhances hypertension-induced left ventricular hypertrophy. In these patients angiotensin-converting enzyme inhibitors are more efficient than beta-blockers in reducing cardiac size.

The use of a telematic connection for the follow-up of hypertensive patients improves the cardiovascular prognosis.

BACKGROUND: Inadequate blood pressure (BP) control could be due to incorrect management of hypertensives caused by the lack of interaction between general practitioners (GP) and hypertension specialists. OBJECTIVES: To test the effectiveness on BP and total cardiovascular risk (TCVR) control of an internet-based digital network connecting specialists and GPs. METHODS: We created a network among the Hypertension Clinic, Federico II University (Naples, Italy), 23 hospital-based hypertension clinics and 60 GPs from the area (CampaniaSalute Network, CS). Randomized GPs enrolled in CS could update online records of patients (n = 1979). As a control, we included 2045 patients referred to the specialist clinics by GPs from outside the network. All patients completed a 2-year follow-up. RESULTS: CS provided a larger reduction in BP [systolic/diastolic BP (SBP/DBP): 7.3 +/- 0.4/5.4 +/- 0.3 versus 4.1 +/- 0.4/3.1 +/- 0.26 mmHg, CS versus control; P < 0.001 for both] and percentage of patients with BP < 140/90 mmHg (CS versus control: baseline, 33 versus 34%, NS; end of follow-up, 51 versus 47%, chi = 13.371; P < 0.001). A European Society of Hypertension-European Society of Cardiology (ESH/ESC) TCVR score was calculated [from 1 (average) to 5 (very high TCVR)]. The CS group showed a reduction in the mean TCVR score (CS: from 3.5 +/- 0.02 to 3.2 +/- 0, P < 0.01, ANOVA; control group: 3.5 +/- 0.03 to 3.4 +/- 0.03, NS) and, accordingly, fatal and non-fatal major cardiovascular events (MACE) were less frequent (2.9 versus 4.3%; chi = 5.047, P < 0.02). CS predicts fewer MACE in multiple binary regression analysis (beta:-7.27, P < 0.008) reducing the risk for MACE compared to control [odds ratio (OR): 0.838; 95% confidence interval (CI): 0.73-0.96]. CONCLUSION: Our results support the idea that telemedicine can achieve better control of BP and TCVR.

The Glu27 allele of the beta2 adrenergic receptor increases the risk of cardiac hypertrophy in hypertension.

OBJECTIVE: Cardiac and vascular remodeling occur in response to hypertension. Genetic background appears to modify the development of target organ damage (TOD). We evaluated the impact on hypertension-associated TOD of a highly polymorphic gene with elevated significance for the regulation of the cardiovascular system, the beta2AR gene. METHODS: We recruited 775 hypertensives (mean +/- SE: age 53.5 +/- 0.5, from 20 to 84 years; female 32.7%; systolic (SBP)/diastolic (DBP) blood pressure: 159 +/- 1.2/101 +/- 0.6 mmHg) referred to the departmental outpatient clinic and screened them for the Arg16Gly, Gln27Glu, and Ile164Thr variants of beta2AR gene. We performed association analyses on clinical, anamnesis, anthropometrical and biochemical parameters as well as cardiac and vascular ultrasound. RESULTS: We found that the three polymorphisms did not affect blood pressure levels. Cardiac TOD appeared to be related to the Glu27 variant. In fact, the Glu27 allele associates with a 1.4-fold higher risk of developing cardiac hypertrophy, and directly correlated with larger systolic and diastolic left ventricle internal diameters. Vascular TOD was not affected by the three polymorphisms. Ancillary to our finding we observed that the Glu27 variant is associated with a higher incidence of dyslipidemia. CONCLUSIONS: Our data indicate that beta2AR gene polymorphisms participate in the determination of cardiac TOD associated with hypertension.

AKT participates in endothelial dysfunction in hypertension.

BACKGROUND: In hypertension, reduced nitric oxide production and blunted endothelial vasorelaxation are observed. It was recently reported that AKT phosphorylates and activates endothelial nitric oxide synthase and that impaired kinase activity may be involved in endothelial dysfunction. METHODS AND RESULTS: To identify the physiological role of the kinase in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), we used adenoviral vectors to transfer the human AKT1 gene selectively to the common carotid endothelium. In vitro, endothelial vasorelaxations to acetylcholine, isoproterenol, and insulin were blunted in control carotids from SHR compared with WKY rats, and human AKT1 overexpression corrected these responses. Similarly, blood flow assessed in vivo by Doppler ultrasound was reduced in SHR compared with WKY carotids and normalized after AKT1 gene transfer. In primary cultured endothelial cells, we evaluated AKT phosphorylation, activity, and compartmentalization and observed a mislocalization of the kinase in SHR. CONCLUSIONS: We conclude that AKT participates in the settings of endothelial dysfunction in SHR rats by impaired membrane localization. Our data suggest that AKT is involved in endothelium dysfunction in hypertension.