Major adverse cardiovascular events associated with VEGF-targeted anticancer tyrosine kinase inhibitors: a real-life study and proposed algorithm for proactive management.

BACKGROUND: Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population. PATIENTS AND METHODS: In this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs. RESULTS: A total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001). CONCLUSIONS: MACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.

Home blood pressure measurement and its relationship with blood pressure control in a large selected hypertensive population.

Despite the impressive increase of home blood pressure monitoring (BPM) among hypertensive patients over the last few years, a limited number of studies have analysed the rate of home BPM and its relationship with target blood pressure (BP) control, in representative samples of the hypertensive population. The objectives of the study were first to evaluate the prevalence of home BPM in a large selected group of treated hypertensive patients referred to our outpatient hypertension hospital clinic. Second, to assess the rate of satisfactory clinic BP control in patients with or without familiarity with home BPM. In all, 1350 consecutive hypertensive patients who attended our hypertension centre during a period of 12 months and were regularly followed up by the same medical team were included in the study. After informed consent all patients underwent the following procedures: (1) accurate medical history (implemented by a structured questionnaire on demographic and clinical characteristics, including questions concerning home BPM); (2) physical examination; (3) clinic BP measurement; (4) routine examinations; and (5) standard 12-lead electrocardiogram. A total of 897 patients (66%) out of 1350 (687 men, 663 women, age 58.6 +/- 12.3 years, mean clinic BP 141 +/- 16/87 +/- 9 mmHg ) were regularly practising home BPM. In this group of patients, home BPM was associated with a significantly greater rate of satisfactory BP control (49.2 vs 45.6%, P < 0.01). Patients performing home BPM were more frequently men (54 vs 46%, P < 0.02 ) younger (average age 57.8 +/- 12.0 vs 60.3 +/- 12.7 years, P < 0.001) and with a higher educational level (defined by more than 8 years of school, 71 vs 55%, P < 0.05) than their counterparts. There were no significant differences in duration of hypertension, hypercholesterolaemia, obesity, smoking, diabetes, associated cardiovascular diseases, left ventricular hypertrophy and compliance with drug treatment. This study demonstrates that: (1) home BPM is widely performed by hypertensive patients managed in a hypertension hospital clinic; (2) this practice is associated with a significantly higher rate of clinic BP control; and (3) age, male gender and educational level influence the adoption of home BPM.

Reduced nocturnal fall in blood pressure, assessed by two ambulatory blood pressure monitorings and cardiac alterations in early phases of untreated essential hypertension.

To investigate whether in recently diagnosed essential hypertensives a reduced nocturnal fall in blood pressure (BP), established on the basis of two 24-h ambulatory blood pressure monitorings (ABPM) is related to a greater cardiovascular damage. In all, 355 consecutive, recently diagnosed, never-treated essential hypertensives referred for the first time to our outpatient clinic were included in the study. Each patient underwent the following procedures: (1) two 24-h ABPMs performed within 3 weeks, (2) 24-h urinary collection for microalbuminuria, (3) nonmydriatic photography of ocular fundi, (4) echocardiography, (5) carotid ultrasonography. We defined nondipping profile as a night-day systolic and diastolic fall < or =10 % (mean of two ABPMs). A dipper BP profile was found in 238 patients, whereas in 117 patients a nondipper profile was present. The two groups were similar for age, gender, body mass index, smoking habit, clinic BP, 48-h BP and heart rate, while, by definition, night-time systolic and diastolic BP were significantly higher in nondippers than in dippers (130/81 vs 121/74 mmHg, P < 0.0001).The prevalence of left ventricular hypertrophy (LVH) defined by four different criteria: (a) LV mass index (LVMI) > or = 125 g/m(2) in both genders; (b) LVMI > or = 134 gm(2) in men and > or = 110 in women; (c) LVMI> or = 125 g/m(2) in men and > or = 110 g/m(2) in women; (d) LVMI > or = 51 g/m(2.7) in men and > or = 47 g/m(2.7) in women was significantly higher in nondippers than in dippers (a: 12 vs 7%, P < 0.05; b: 16 vs 7%, P < 0.01; c: 20 vs 11%, P < 0.01; d: 35 vs 23% P < 0.02) and this finding was associated with a significant increase in aortic root and left atrium dimensions. There were no differences between the two groups in the prevalence of carotid and retinal changes and microalbuminuria. In conclusion our findings suggest that never-treated hypertensives with a reduced BP fall in the night time, defined on the basis of two ABPMs, have a higher prevalence of TOD than dippers, in terms of echocardiographic LVH. In this population setting, cardiac structural alterations are a more sensitive marker of the impact of the nocturnal BP load on cardiovascular system than other extracardiac signs of TOD.

High prevalence of cardiac and extracardiac target organ damage in refractory hypertension.

OBJECTIVE: Target organ damage (TOD) in chronically treated hypertensives is related to effective blood pressure (BP) control. The aim of this study was to evaluate the prevalence of cardiac and extracardiac TOD in patients with refractory hypertension (RH) compared with well-controlled treated hypertensives (C). METHODS: Fifty-four consecutive patients with RH (57 +/- 10 years), selected according to WHO/ISH guidelines definition, and 51 essential hypertensives (55 +/- 10 years) with satisfactory BP control obtained by association therapy, underwent the following procedures: (1) clinic BP measurement; (2) blood sampling for routine chemistry examinations; (3) 24 h urine collection for microalbuminuria; (4) non-mydriatic retinography; (5) echocardiogram; (6) carotid ultrasonogram. In order to exclude 'office resistance' (defined as clinic BP > 140/90 mmHg and average 24 h BP or =1.0 mm, respectively); a higher prevalence of carotid plaques (65 versus 32%, P < 0.05), a more advanced retinal involvement (grade II and III, 73 and 5% versus 38 and 0%, P < 0.01) and a greater albumin urinary excretion (22 +/- 32 mg/24 h versus 11 +/- 13 mg/24 h, P < 0.01) were found in RH compared to C. CONCLUSIONS: Our study suggests that RH is a clinical condition associated with a high prevalence of TOD at cardiac, macro- and microvascular level and consequently with high absolute cardiovascular risk, which needs a particularly intensive therapeutic approach aimed to normalize BP levels and to induce TOD regression.

Target organ damage and non-dipping pattern defined by two sessions of ambulatory blood pressure monitoring in recently diagnosed essential hypertensive patients.

OBJECTIVE: To evaluate in a selected population of patients with a recent diagnosis of hypertension whether a reduced nocturnal fall in blood pressure, confirmed by two 24 h ambulatory blood pressure monitoring (ABPM) sessions is associated with more prominent target organ damage (TOD). METHODS: The study was structured in two phases: in the first, 141 consecutive, recently diagnosed, never-treated essential hypertensives underwent 24 h ABPM twice within 3 weeks; in the second phase, 118 of these patients showing reproducible dipping or non-dipping patterns underwent the following procedures: (1) routine blood chemistry, (2) 24 h urinary collection for microalbuminuria, (3) amydriatic photography of ocular fundi, (4) echocardiography and (5) carotid ultrasonography. RESULTS: The 92 patients with (>10%) night-time fall in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (dippers) in both monitoring sessions were similar for age, gender, body surface area, smoking habit, clinic BP, 24 h and 48 h BP to the 26 patients with a < or = 10% nocturnal fall (non-dippers) in both sessions. The prevalence of left ventricular hypertrophy (LVH) (defined by two criteria: (1) LV mass index > or = 125 g/m2 in both genders; (2) LV mass index > or = 120 and 100 g/m2 in men and women, respectively) and that of carotid intima-media (IM) thickening (IM thickness > or = 0.8 mm) were significantly higher in non-dippers than in dippers (23 versus 5%, P < 0.01; 50 versus 22%, P < 0.05; and 38 versus 18%, P < 0.05, respectively). There were no differences among the two groups in the prevalence of retinal changes and microalbuminuria. The strength of the association of LV mass index with night-time BP was slightly but significantly greater than that with daytime BP. CONCLUSIONS: This study suggests that a blunted reduction in nocturnal BP, persisting over time, may play a pivotal role in the development of some expressions of TOD, such as LVH and IM thickening, during the early phase of essential hypertension, despite similar clinic BP, 24 h and 48 h BP levels observed in non-dippers and dippers.