Alfonso Alfieri

Is insulin action a determinant of left ventricular relaxation in uncomplicated essential hypertension

Objective To examine the relation of insulin action and left ventricular diastolic function in uncomplicated essential hypertension. Methods Doppler echocardiography and glucose clamping combined with indirect calorimetry were performed in 29, newly diagnosed, hypertensive men, free from cardiac and metabolic drugs. They were divided into two groups according to the clamp-derived whole-body glucose disposal level: 20 with insulin resistance (whole-body glucose disposal < 33 μmol/kg per min) and nine with normal insulin sensitivity. Results The two groups were comparable in age, body mass index, heart rate and blood pressure. No difference in diastolic function was found except for the isovolumic relaxation time, which was prolonged for patients with insulin resistance (P = 0.02). For the population as a whole, the relaxation time had univariate relations with the left ventricular mass index (r = 0.57, P < 0.001), whole-body glucose disposal (r = −0.56, P < 0.001) and non-oxidative glucose metabolism (r = −0.54, P = 0.002). In a multivariate model including age, body mass index, heart rate, diastolic blood pressure, left ventricular mass index and whole-body glucose disposal as potential determinants, only the left ventricular mass index (β = 0.39, P = 0.02) and whole-body glucose disposal (β = −0.38, P = 0.03) were independent predictors of the relaxation time (R2 = 0.43, P < 0.001). Conclusions In uncomplicated essential hypertension the insulin resistance is a determinant of abnormalities in isovolumic relaxation, independently from the influence exerted by increased blood pressure levels, being overweight and left ventricular hypertrophy.

Impact of ambulatory blood pressure on left ventricular diastolic dysfunction in uncomplicated arterial systemic hypertension

To determine the relations of 24-hour blood pressure (BP) and its different phases with left ventricular (LV) diastolic filling, 125 subjects (mean age 46 years) not taking cardiac drugs were studied by Doppler echocardiography and ambulatory BP recording. Subjects (excluding those with coronary artery or valvular heart disease, heart failure, or diabetes) were classified into 2 groups according to the level of Doppler-derived ratio of peak early to atrial velocity (E/A ratio): 59 had E/A >1 (normal diastole), 62 had E/A <1 (impaired diastole), and 4 had E/A = 1. Patients with E/A <1 were older and had higher LV mass indexed for height, average 24-hour BP, average nighttime BP, and lower day-night BP decrease, whereas average daytime BP did not differ significantly between the 2 groups. Negative correlations of E/A were found with age, heart rate, office, average 24-hour and average nighttime systolic and diastolic BP, and LV mass index. In a multivariate model that included potentially confounding factors, only age (standardized beta coefficient = -0.52, p<0.00001), nighttime BP (beta = -0.28, p<0.0001), and heart rate (beta = -0.22, p<0.001) were independent predictors of E/A in the pooled population. In conclusion, LV diastolic function is more closely related to ambulatory, rather than to clinic, BP measurements, and high average nocturnal diastolic BP is a powerful marker of LV filling impairment.

Influence of nighttime blood pressure on left atrial size in uncomplicated arterial systemic hypertension

The aim of the study was to determine the relations of 24-h blood pressure (BP) and its different phases with left atrial size. A total of 130 subjects (mean age 46 years) not taking cardiac drugs were studied by M-mode and Doppler echocardiography and ambulatory BP recording. Subjects (excluding those with coronary artery or valvular heart disease, heart failure, or diabetes) were classified into two groups: 25 normotensives and 105 hypertensives (history of antihypertensive treatment and office diastolic BP > 90 mm Hg). The two groups were comparable in terms of sex, age, and heart rate, whereas body mass index, (P < .01), office BP, average 24-h BP, and average daytime and nighttime BP (all P < .00001) were higher in hypertensives. Hypertensives also had increased left atrial dimension, left atrial dimension/aortic root ratio (both P < .001), and left ventricular mass (LV) indexed for height (P < .0001). Positive correlations of left atrial dimension were found with office BP, average 24-h, average daytime and nighttime systolic and diastolic BP, LV mass index, and Doppler-derived E/A ratio. In a multivariate model that included potentially confounding factors, only body mass index (standardized beta coefficient = 0.41, P < .00001), average nighttime diastolic BP (beta = 0.33, P < .00001), and male sex (beta = 0.18, P < .01) were independent predictors of left atrial size in the pooled population. In conclusion, left atrial size is more closely related to ambulatory, rather than office, BP measurements, and high average nighttime BP is a powerful marker of left atrial enlargement in arterial hypertension.

Reduced antiplatelet therapy after drug-eluting stenting: multicenter Janus Flex carbostent implantation with short dual antiplatelet treatment for 2 or 6 months-MATRIX study.

Objectives: The Multicentre registry with Antiplatelet TReatment two–sIX months (MATRIX) evaluated safety and efficacy at 12‐month follow‐up of Janus Flex stenting with 2‐ or 6‐month dual antiplatelet therapy (DAT) period. Background: There are no data of Janus Flex stent (Carbostent and Implantable Devices—CID, Saluggia, Italy), a polymer‐free, tacrolimus‐eluting coronary stent, followed by short‐term DAT, in daily practice. Methods: Patients were prospectively enrolled at 12 high‐volume procedures centres. After stenting, four sites prescribed 2‐month DAT, eight sites 6‐month DAT. Major adverse cardiac events (MACE) and stent thrombosis (ST) rate was evaluated at 12‐month follow‐up, for entire population, as well as for 2‐ and 6‐month DAT groups, distinctly. MACE included cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR). Results: From March 2007 to June 2008, 572 patients (mean age 64.91 ± 11 years, 77.45% males) were enrolled. After successful stenting, 12‐month follow‐up showed a 12.74% MACE occurrence (cardiac death 0.98%; MI 3.13%; TLR 8.62%), with good Janus Flex safety profile confirmed by only two (0.39%) ST. After adjustment for potential confounding, no significant differences were noted at 12‐month follow‐up among 2‐ or 6‐month DAT groups (MACE—8.99% versus 12.47%, P = 0.16; cardiac death—0.54% versus 1.14%, P = 0.52; MI—2.38% versus 2.71%, P = 0.83; TLR—5.66% versus 10.60%, P = 0.20; ST—0% versus 0.55%, P = 0.99). At multivariable analysis, DAT time duration was not an independent risk factor for adverse events (adjusted HR 0.47, 95% confidence interval 0.16–1.35, P = 0.16). Conclusions: Janus Flex coronary stenting, followed by short DAT, is safe and feasible, without differences between 2‐ and 6‐month DAT groups. A randomized trial confirming these encouraging data is needed.

Comparative evaluation of the antihypertensive efficacy of once-daily sustained-release isradipine and lacidipine using 24-hour ambulatory blood-pressure monitoring

In this single-blind crossover study the antihypertensive efficacies of two dihydropyridine calcium antagonists, sustained-release isradipine and lacidipine, were compared using clinic and ambulatory blood-pressure measurements. After a 2-week placebo wash-out, 34 patients (19 men, 15 women, mean age 49 years) with mild to moderate hypertension (diastolic blood pressure range 95 – 110 mmHg) were treated with 5 mg sustained-release isradipine for 4 weeks and 4 mg lacidipine for 4 weeks in a random order. Medications were taken once daily at 08.00 h. Clinic and ambulatory blood pressures were recorded at the end of each placebo or treatment period. Two patients stopped isradipine and six lacidipine because of severe adverse effects. Clinic systolic and diastolic blood pressures decreased by an average of 17/14 mmHg with isradipine and 17/13 mmHg with lacidipine, compared with placebo (P < 0.01 in both cases), without a change in heart rate. Mean ambulatory 24-h and daytime systolic and diastolic blood pressure were significantly reduced by sustained-release isradipine and lacidipine (P < 0.05 and P < 0.01, respectively). At night systolic blood pressure fell compared with placebo (P < 0.05 with both drugs) whereas the reduction in diastolic blood pressure was not statistically significant. Mean 24-h heart rate remained unchanged. Blood-pressure variability did not differ significantly between the two drugs or between either drug and the placebo. The antihypertensive effects of sustained-release isradipine and lacidipine were similar, but the tolerability of isradipine appears to be greater since it caused fewer withdrawals.