Barbara Citoni

Adding markers of organ damage to risk score models improves cardiovascular risk assessment: Prospective analysis of a large cohort of adult outpatients

INTRODUCTION Global cardiovascular (CV) risk stratification is recommended in all outpatients. Risk score charts, however, do not include markers of organ damage (OD). AIM To evaluate the potential added value of including different markers of subclinical OD to US Framingham, European SCORE and Italian Cuore risk score calculators. METHODS We prospectively evaluated adult outpatients, who underwent blood pressure (BP) assessment and global CV risk stratification. The following OD markers were considered: 1) cardiac OD: electrocardiographic) or echocardiographic left ventricular (LV) hypertrophy; 2) vascular OD: carotid atherosclerotic plaque; 3) renal OD: reduced estimated glomerular filtration rate or creatinine clearance. Different risk score calculators were applied for comparisons. RESULTS We included an overall population sample of 1979 outpatients (44.0% female, age 57.2±13.0years, BMI 26,6±4,4kg/m2, clinic systolic/diastolic BP 145.4±18.3/85.8±10.7mmHg), among whom 117 (5.9%) presented cardiac, 161 (8.1%) vascular, and 117 (5.9%) renal OD. US Framingham, European SCORE and Italian Cuore risk scores were all significantly raised in patients with than in those without OD. A trend toward increase for US Framingham CVD death, European ESC and Italian Cuore scores was observed according to degree of all markers of OD. Among these, reduced ClCr and eGFR showed high sensitivity and specificity to identify high risk individuals. CONCLUSIONS Presence of cardiac, vascular or renal OD is associated with higher risk scores, independently by the types of calculators, age and gender classes. OD detection should be included in CV risk stratification in order to improve diagnostic, prognostic and therapeutic processes.

Favourable impact of statin use on diastolic blood pressure levels: Analysis of a large database of 24-hour ambulatory blood pressure monitoring

Introduction: Assumption of lipid-lowering drugs, mostly statins, is recommended at bed-time and evidence demonstrated a strong and independent correlation between night-time blood pressure (BP) and increased risk of cardiovascular events. Aim: To evaluate the effects of statins on night-time BP levels. Methods: We analysed data derived from a large cohort of adult individuals, who consecutively underwent home, clinic and ambulatory BP monitoring at our Unit. All BP measurements were performed and BP thresholds were set according to recommendations from European guidelines. Study population was stratified according to statin use. Results: We included an overall sample of 5634 adult individuals (women 48.9%, age 60.5 ± 11.6 years, BMI 27.0 ± 4.6 kg/m2, clinic BP 144.3 ± 18.4/90.9 ± 12.4 mmHg, 24-h BP 130.7 ± 13.4/79.0 ± 9.7 mmHg), among whom 17.3% received and 82.7% did not received statins. Treated outpatients were older, had higher BMI and prevalence of risk factors and comorbidities than those who were untreated (P < 0.001 for all). Patients treated with statins showed lower DBP levels at all BP measurements, including night-time (67.3 ± 9.4 vs. 70.9 ± 9.7 mmHg; P < 0.001) periods, than those observed in untreated patients. Also, statin use resulted an independent factor associated with 24-h [odds ratio (95% confidence interval): 1.513(1.295–1.767); P < 0.001] and night-time [odds ratio (95% confidence interval): 1.357(1.161–1.587); P < 0.001] BP control, even after adjusting for age, sex, BMI, diabetes, number of antihypertensive drugs (model 1) or presence/absence of antihypertensive treatment (model 2). Conclusion: Statin use was associated with significantly lower DBP levels. These effects were independently observed, even after correction for cardiovascular risk factors and comorbidities, as well as number of antihypertensive drugs.

Clinical management of patients with hypertension and high cardiovascular risk in specialised centers and in general practice. Analysis from an Italian Survey Questionnaire.

BACKGROUND AND AIM Hypertension control remains poorly achieved worldwide, despite the use of modern diagnostic tools and advanced therapeutic strategies. We aimed to evaluate the preferences expressed by either specialised physicians (SPs) or general practitioners (GPs) for the clinical management of hypertension and high cardiovascular risk in Italy. METHODS AND RESULTS A predefined questionnaire was anonymously administered to a large community sample of physicians, stratified according to clinical expertise. From a total of 64 questions, 557 physicians (478 male, mean age 54.2 ± 7.1 years, average age of medical activity 28.0 ± 8.1 years), including 261 (46.9%) SPs and 296 (53.1%) GPs, provided 9564 answers to the survey questionnaire. Involved clinicians spent the majority of their time and practice for hypertension management and control. SPs aimed to achieve the recommended BP targets (<140/90 mmHg), whereas GPs tended to achieve more rigorous BP goals (<130/80 mmHg); nonetheless, they both reported a very high rate of BP control (about 70%). Concomitant presence of diabetes, organ damage, as well as comorbidities, was reported to be relatively frequent (26-50%), mostly by SPs. ESH/ESC 2007 risk score stratification was preferred by SPs compared to GPs, who favored a comprehensive clinical evaluation. ACE inhibitors or ARBs were considered the best pharmacological option to start antihypertensive treatment, thus adding diuretics or calcium-channel blockers, if needed. CONCLUSIONS This predefined analysis of a survey questionnaire showed relatively different opinions with respect to recommended BP targets and distributions of cardiovascular risk profile, and similar diagnostic and therapeutic choices between GPs and SPs.

Achievement of multiple therapeutic targets for cardiovascular disease prevention: Retrospective analysis of real practice in Italy

Pharmacological therapy in patients at high cardiovascular (CV) risk should be tailored to achieve recommended therapeutic targets.

Effects of different statin types and dosages on systolic/diastolic blood pressure: Retrospective analysis of 24-hour ambulatory blood pressure database

We previously demonstrated lower diastolic blood pressure (BP) levels under statin therapy in adult individuals who consecutively underwent 24‐hour ambulatory BP monitoring and compared their levels to untreated outpatients. Here we evaluated systolic/diastolic BP levels according to different statin types and dosages. 987 patients (47.5% female, age 66.0 ± 10.1 years, BMI 27.7 ± 4.6 kg/m2, clinic BP 146.9 ± 19.4/86.1 ± 12.1 mm Hg, 24‐hour BP 129.2 ± 14.4/74.9 ± 9.2 mm Hg) were stratified into 4 groups: 291 (29.5%) on simvastatin 10‐80 mg/d, 341 (34.5%) on atorvastatin 10‐80 mg/d, 187 (18.9%) on rosuvastatin 5‐40 mg/d, and 168 (17.0%) on other statins. There were no significant BP differences among patients treated by various statin types and dosages, except in lower clinic (P = .007) and daytime (P = .013) diastolic BP in patients treated with simvastatin and atorvastatin compared to other statins. Favorable effects of statins on systolic/diastolic BP levels seem to be independent of types or dosages, thus suggesting a potential class effect of these drugs.

Nocturnal blood pressure patterns and cardiovascular outcomes in patients with masked hypertension

Masked hypertension (MHT) is characterized by normal clinic and above normal 24‐hour ambulatory blood pressure (BP) levels. We evaluated clinical characteristics and CV outcomes of different nocturnal patterns of MHT. We analyzed data derived from a large cohort of adult individuals, who consecutively underwent home, clinic, and ambulatory BP monitoring at our Hypertension Unit between January 2007 and December 2016. MHT was defined as clinic BP <140/90 mm Hg and 24‐hour BP ≥ 130/80 mm Hg, and stratified into three groups according to dipping status: (a) dippers, (b) nondippers, and (c) reverse dippers. From an overall sample of 6695 individuals, we selected 2628 (46.2%) adult untreated individuals, among whom 153 (5.0%) had MHT. In this group, 67 (43.8%) were nondippers, 65 (42.5%) dippers, and 21 (13.7%) reverse dippers. No significant differences were found among groups regarding demographics, clinical characteristics, and prevalence of risk factors, excluding older age in reverse dippers compared to other groups (P < 0.001). Systolic BP levels were significantly higher in reverse dippers than in other groups at both 24‐hour (135.6 ± 8.5 vs 130.4 ± 6.0 vs 128.2 ± 6.8 mm Hg, respectively; P < 0.001) and nighttime periods (138.2 ± 9.1 vs 125.0 ± 6.3 vs 114.5 ± 7.7 mm Hg; P < 0.001). Reverse dipping was associated with a significantly higher risk of stroke, even after correction for age, gender, BMI, dyslipidemia, and diabetes (OR 18.660; 95% IC [1.056‐33.813]; P = 0.046). MHT with reverse dipping status was associated with higher burden of BP and relatively high risk of stroke compared to both dipping and nondipping profiles, although a limited number of CV outcomes have been recorded during the follow‐up.

Hypertension Across the Atlantic: A Sprint or a Marathon?

Last year, in the middle of September, a sudden scientific storm hit North America and the world of hypertension. Somehow unconventionally, the New York Times newspaper announced for the first time in an article for the lay public the surprising results of the Systolic Blood Pressure Intervention Trial (SPRINT) [1], a large, randomized, controlled clinical trial performed under the auspices of the National Institute of Health (NIH) in the United States. The most astonishing part of this article reported the beneficial effects of reaching 120 mmHg of systolic blood pressure (BP). The SPRINT trial was aimed at exploring whether the achievement of an ambitious BP target that was, indeed, 120 mmHg or less for the systolic would bring an advantage in reducing the risk of cardiovascular disease [1]. The benchmark for the comparison was the conventional systolic BP normality threshold of less than 140 mmHg, heralded for more than 10 years as one of the few ‘‘mantra’’ in hypertension in a number of European and North American guidelines sets [2–9]. Definitive scientific results of the trial were finally presented in the Late Breaking Section at the American Heart Association Scientific Sessions and simultaneously published on the New England Journal of Medicine in the middle of November [10]. Some of the very specific features of the population of SPRINT sounded reassuring, at a first sight, for the hypertension scientific community, in spite of the quite astonishing results. In fact, some of the choices in the features of the population included in the trial had led to a design enrolling only hypertensive patients ‘‘crawling’’ in the high-normal range of systolic BP. Moreover, people with difficult-to-treat hypertension were surprisingly excluded from the trial. Furthermore, the 9361 hypertensive patients enrolled were aged more than 50 years, excluding history of diabetes or prior stroke, though featuring a high cardiovascular risk, as defined by one or more of the following items: clinical or subclinical cardiovascular disease other than stroke, chronic kidney disease, excluding polycystic kidney disease, with an estimated glomerular filtration rate between 20–60 ml/min/1.73 m of body surface area, and exceeding 15% of estimated risk, according to Framingham Score [11]. The main conclusions of the SPRINT investigators were that more aggressive BP reductions would led to beneficial and significant effects on cardiovascular accidents, mostly heart failure and cardiovascular and non-cardiovascular death, compared to conventional BP targets [10]. On the other hand, these results would probably be the subject of a cautious reappraisal next year (2 years after this breakthrough publication of SPRINT trial), with a much more conservative pace (like the one you use in ‘‘marathons’’). In the meantime, a number of publications raised ‘‘lethal’’ criticisms to SPRINT design, methods and conclusions [12–16]. We must say, for the sake of our readers, that some of these criticisms were appropriate and we decided to list them below. First of all, the authors of SPRINT, prompted by a not really timely need to measure BP levels in the ‘‘best way’’, adopted in the study protocol a method now defined ‘‘unattended measurement of BP levels’’. According to this methodology, all enrolled patients were left alone in a quiet & Massimo Volpe massimo.volpe@uniroma1.it