A subgroup analysis of the ODYSSEY APPRISE study: Safety and efficacy of alirocumab in the Italian cohort.

BACKGROUND AND AIMS: ODYSSEY APPRISE trial evaluated efficacy and safety of alirocumab in 994 patients with hypercholesterolemia and high CV risk in a real-life setting. The aim of the present report is to detail on the Italian cohort enrolled and treated in the trial. METHODS AND RESULTS: The methodology of the of the multinational, single-arm, Phase 3b open-label ODYSSEY APPRISE (Clinicaltrials.gov: NCT02476006) has been previously reported. 255 Italian patients were enrolled and treated according to the trial protocol. Overall mean exposure to alirocumab was 83.3 ± 27.7 weeks. At week 12, LDL-C decreased by 51.3 ± 23.1% and this reduction was overall maintained for the duration of the study. A similar reduction was observed in patients with and without heterozygous familial hypercholesterolemia (HeFH 50.7% ± 23.9 vs. non-FH, 53.6% ± 19.6). LDL-C was reduced below 1.8 mmol/L and/or by ≥ 50% reduction from baseline in 62% of patients overall (61% in HeFH and 67% in non-FH). Alirocumab was similarly well tolerated in the Italian cohort as in the entire study population and the more common treatment emergent adverse events (TEAEs) were influenza, myalgia and nasopharyngitis. The incidence LDL-C levels <25 mg/dl and <15 mg/dl, was 8.2% and 2.9% respectively. CONCLUSION: The efficacy and safety of alirocumab in a real-life setting, in the Italian subgroup of patients are consistent with findings in the entire study population and confirm that alirocumab is a beneficial approach to further reduce LDL-C levels in patients at high CV risk on maximally tolerated conventional lipid lowering treatment. GOV IDENTIFIER: NCT02476006.

Evolution of blood pressure and cholesterol in stage 1 hypertension: role of autonomic nervous system activity.

OBJECTIVE: Controversy remains concerning the pathogenetic mechanisms for the relationship between sympathetic activity, hypertension and lipid abnormalities. We tested the hypothesis that a condition characterized by sympathetic predominance may affect the evolution of blood pressure and lipids in the early stage of hypertension. METHODS: We prospectively studied 163 young stage 1 hypertensive individuals and 28 normotensive control individuals. The hypertensive subjects were divided by cluster analysis into two groups according to low frequency and high frequency components of heart rate variability. Large artery and small artery compliance was assessed at the end of the follow-up. RESULTS: Fifty-nine subjects showed reduced total power and signs of sympathetic predominance in the resting condition, on standing and during mental stress (group 1). At baseline, they had similar blood pressure and metabolic data to the rest of the group (n = 104, group 2) and a greater white-coat effect (P = 0.03). During a 6-year follow-up, 23.7% of group 1 subjects versus 9.6% of group 2 subjects developed sustained hypertension requiring antihypertensive treatment (P = 0.02). In group 1 subjects, there was also a greater increase in total cholesterol (P = 0.01) than in group 2. In addition, at the end of follow-up group 1 subjects had impaired large artery compliance (P < 0.001 versus group 2). CONCLUSIONS: These data indicate that a condition characterized by sympathetic predominance may favour the development of sustained hypertension and hypercholesterolemia early in life, and lead to increased susceptibility to vascular complications. They further indicate that the increased white-coat effect is not an innocent phenomenon.

Impaired arterial elasticity in young patients with white-coat hypertension.

BACKGROUND: Conflict still exists over whether patients with white-coat hypertension are at increased risk of developing target organ damage compared with normotensive individuals. METHODS: We studied vascular distensibility in 117 young-to-middle age patients with white-coat hypertension, 174 patients with sustained hypertension, and 51 normotensive controls. To obtain a measure of compliance, a model was used that divides the total systemic compliance into large artery (C1) and small artery (C2) compliance. With this aim, radial arterial pulse waves were recorded with a tonometer sensor array by means of an HDI CR2000 device (Eagan, Minnesota, USA). Moreover, pulse wave velocity and the augmentation index were measured using the Specaway DAT system (St Pauls, Sydney, Australia). RESULTS: Patients with sustained hypertension had a greater body mass index than patients with white-coat hypertension (P=0.04) or the normotensive individuals (P=0.01). C1 and C2 were decreased in the two hypertensive groups as compared with those in the normotensive group (P=0.0002 and 0.03, respectively, versus sustained hypertension; P=0.00007 and 0.0004, respectively, versus white-coat hypertension). Pulse wave velocity and aortic augmentation index were increased in the white-coat hypertension patients compared with the normotensive individuals (P=0.02 and 0.004, respectively). Aortic augmentation index (P=0.008) but not pulse wave velocity was increased in the sustained hypertensive patients compared with that in the normotensive individuals. All indexes of arterial distensibility were similar in the two hypertensive groups. CONCLUSIONS: Indexes of arterial distensibility are impaired in the white-coat hypertensive group and similar to those in the sustained hypertensive group, indicating that early changes in the arterial wall can occur in white-coat hypertension. This may account for the higher risk of stroke that has been described in this condition.

Microalbuminuria, renal function and development of sustained hypertension: a longitudinal study in the early stage of hypertension.

OBJECTIVE: Microalbuminuria (MA) is a marker of adverse outcome in hypertension. The aim of this study was to investigate the association of MA with cardiovascular risk factors and glomerular hyperfiltration in the early stage of hypertension and to assess its predictive value for the development of sustained hypertension requiring antihypertensive treatment. DESIGN AND PARTICIPANTS: We studied 1041 young stage 1 hypertensive subjects. Study variables were 24-h ambulatory blood pressure and heart rate, anthropometric measures, metabolic variables, creatinine clearance and lifestyle factors analyzed as a function of ascending urinary albumin measured from 24-h collections. Subjects were followed until they developed sustained hypertension and were eligible for antihypertensive medication according to current guidelines. SETTING: Seventeen outpatient clinics in Italy. RESULTS: Eighty-five percent of the subjects were normoalbuminuric, 9% had borderline MA, and 6% had overt MA. No between-group differences were found for age, body mass index, heart rate, lifestyle factors and biochemistry in both genders. Creatinine clearance was greater in the subjects with overt MA and borderline MA than in the normoalbuminuric subjects (P = 0.003 and 0.011, respectively). In a two-way ANCOVA, microalbuminuric subjects both with hyperfiltration (P < 0.001) and with normal filtration (P = 0.04) had higher 24-h systolic blood pressure than subjects with normoalbuminuria and normal filtration. In a Cox analysis, neither MA nor hyperfiltration were significant predictors of development of sustained hypertension. CONCLUSION: MA is not associated with an adverse metabolic risk profile in the early stage of hypertension. MA is associated with greater hemodynamic load and with glomerular hyperfiltration in this clinical setting, but does not help in predicting those subjects destined to develop sustained hypertension requiring antihypertensive therapy.

Performance of the UA-787 oscillometric blood pressure monitor according to the European Society of Hypertension protocol.

OBJECTIVE: To determine the accuracy of the UA-787 oscillometric blood pressure monitor developed by the A&D Company. DESIGN: Evaluation of the UA-787 was performed using the new protocol of the European Society of Hypertension. The performance of the monitor was assessed in relation to the subjects' gender, age, skinfold thickness, arm circumference, body mass index and elasticity index of large (C1) and small (C2) arteries. METHODS: The UA-787 monitor was assessed according to European Society of Hypertension requirements, which are based on four zones of accuracy differing from the mercury standard by 5, 10, 15 mmHg, or more. In all subjects (n=33), indices of large-artery elasticity (C1) and small-artery elasticity (C2) were measured with the HDI/Pulsewave CR-2000 Research Cardiovascular Profiling System. RESULTS: The UA-787 passed all three phases of the protocol for both systolic and diastolic blood pressure. The mean blood pressure difference between device and the observers was 1.0+/-5.3 mmHg for systolic pressure, and 0.7+/-5.3 mmHg for diastolic pressure. In univariate analysis, the discrepancy between device and the observers was related to forearm circumference (P=0.02) for systolic pressure. For diastolic blood pressure, a significant relationship was found only for heart rate (P<0.01). However, in a multivariable regression analysis no clinical variable was an independent predictor of device-observer discrepancy. In particular, the performance of the UA-787 appeared to be uniform across the whole range of C1 and C2. CONCLUSIONS: These data show that the A&D UA-787 device satisfies the new recommended European Society of Hypertension accuracy levels for both systolic and diastolic pressure. Its performance is uniform across sub-groups of subjects with different clinical characteristics.