Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

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

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