Roberta Coluccia

Left ventricular mass increase is associated with cognitive decline and dementia in the elderly independently of blood pressure

AIMS Left ventricular (LV) mass increase is considered part of composite target organ damage in hypertension and an independent risk factor for cardiovascular (CV) events. This study was designed to explore whether left ventricular mass index (LVMI) is associated with cognitive decline and dementia in elderly subjects, independently of blood pressure (BP) levels. METHODS AND RESULTS Four hundred subjects (mean age 79 +/- 6 years) were studied. Left ventricular mass was measured echocardiographically in accordance with American Society of Echocardiography and normalized for body height to the 2.7 (LVMI). Global cognitive function was evaluated with the mini-mental state examination (MMSE) (maximum score 30). Dementia was defined as an MMSE score <21. Arterial stiffness was evaluated as carotid-femoral pulse wave velocity by Complior. Prevalence of hypertension was 70% and diabetes mellitus was diagnosed in 25%. No significant differences in traditional CV risk factors were observed across LVMI quartiles. Mini-mental state examination showed an inverse trend across LVMI quartiles (the higher the LVMI, the lower the MMSE, P for trend <0.05); systolic and diastolic BP levels were not different across LVMI quartiles. In multivariable logistic regression models, including age, sex, BP levels, and use of antihypertensive drugs as covariates, the highest LVMI was found to be independently associated with a two-fold higher likelihood of having dementia. The association persisted significant even after adjustment for arterial stiffness. CONCLUSION In elderly subjects, LVMI is associated with a progressive cognitive decline. This association is independent of BP levels and/or large artery stiffness.

Pathogenesis of Chronic Cardiorenal Syndrome: Is There a Role for Oxidative Stress?

Cardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. Complex biochemical, hormonal and hemodynamic mechanisms underlie the development of cardiorenal syndrome. Both in vitro and experimental studies have identified several dysregulated pathways in heart failure and in chronic kidney disease that lead to increased oxidative stress. A decrease in mitochondrial oxidative metabolism has been reported in cardiomyocytes during heart failure. This is balanced by a compensatory increase in glucose uptake and glycolysis with consequent decrease in myocardial ATP content. In the kidneys, both NADPH oxidase and mitochondrial metabolism are important sources of TGF-β1-induced cellular ROS. NOX-dependent oxidative activation of transcription factors such as NF-kB and c-jun leads to increased expression of renal target genes (phospholipaseA2, MCP-1 and CSF-1, COX-2), thus contributing to renal interstitial fibrosis and inflammation. In the present article, we postulate that, besides contributing to both cardiac and renal dysfunction, increased oxidative stress may also play a crucial role in cardiorenal syndrome development and progression. In particular, an imbalance between the renin-angiotensin-aldosterone system, the sympathetic nervous system, and inflammation may favour cardiorenal syndrome through an excessive oxidative stress production. This article also discusses novel therapeutic strategies for their potential use in the treatment of patients affected by cardiorenal syndrome.

Polypharmacy in heart failure patients.

In heart failure (HF), the progressive use of multiple drugs and a complex therapeutic regimen is common and is recommended by international guidelines. With HF being a common disease in the elderly, patients often have numerous comorbidities that require additional specific treatment, thus producing a heavy pill burden. Polypharmacy, defined as the chronic use of five or more medications, is an underestimated problem in the management of HF patients. However, polypharmacy has an important impact on HF treatment, as it often leads to inappropriate drug prescription, poor adherence to pharmacological therapies, drug-drug interactions, and adverse effects. The growing complexity of HF patients, whose mean age increases progressively and who present multiple comorbidities, suggests the need for newer models of primary care to improve the management of HF patients. Self-care, telemonitoring, and natriuretic peptide-guided therapy represent promising new HF care models to face the complexity of the disease and its therapeutic regimen.

Depression is associated with increased occurrence of left ventricle concentric geometry in older subjects independently of blood pressure levels

BACKGROUND AND AIM Depression is emerging as an independent risk factor for CV events, though mechanisms underlying this association are unknown. We investigated the relation between depression and LV hypertrophy (LVH) and LV structure in a group of elderly subjects. METHODS AND RESULTS Three hundred seventy patients (mean age 79 ± 6 years) were enrolled. CV risk factors were assessed. Depression was defined as a score ≥ 6 on the 15-item Geriatric Depression Scale. On the basis of the presence of LVH and of LV relative wall thickness (RWT) 4 echocardiographic patterns of LV adaptation were defined: concentric LVH (LVH with increased RWT); eccentric LVH (LVH with normal RWT); concentric LV remodeling (no LVH with increased RWT); normal LV (no LVH with normal RWT). Prevalence of hypertension was approximately 86% and 24.7% had diabetes (n.s. depressed vs not depressed subjects). BP was comparable in these two groups (134.7 ± 1.4 vs 135.3 ± 1.8 mmHg, 77.1 ± 0.8 vs 76.3 ± 1.0 mmHg for SBP and DBP respectively). Depressed subjects (n = 165) showed a significantly higher occurrence of concentric LVH than not depressed, after adjustment for age, sex, and hypertension. Depression was associated with a 2.1 fold higher risk of showing a LV concentric, either remodeling or LVH, pattern after adjustment for age, sex, and traditional CV risk factors. CONCLUSIONS Depression is accompanied by a higher occurrence of concentric LVH in elderly subjects, independently of BP levels.

Blood Pressure Levels at the Time of Percutaneous Coronary Revascularization and Risk of Coronary In-Stent Restenosis

BACKGROUND High blood pressure (BP) levels expose patients treated with percutaneous coronary interventions (PCI) to very high risk of 10-year cardiovascular morbidity and mortality. OBJECTIVE To investigate the role of BP levels at the time of PCI on the risk of in-stent restenosis (ISR). METHODS We retrospectively included 796 patients previously treated with PCI, who underwent repeated angiography for recurrent angina or reversible myocardial ischemia. Patients were stratified into either case (n = 354) and control (n = 442) groups in the presence or absence of ISR (defined as in-stent diameter stenosis ≥50%). BP levels were measured at the time of first and second procedures. Normal BP levels were defined for <140/90 mm Hg. RESULTS Patients with normal BP showed significantly higher ISR-free survival (Log-rank: 5.937; P = 0.015). Both systolic (HR (95% CI): 0.731 (0.590-0.906)) and systolic/diastolic BP (HR (95% CI): 0.757 (0.611-0.939)) were significantly and independently associated with lower risk of ISR at Cox-regression analysis, adjusted for potential confounding factors, including stent type and concomitant medications. Patients with ISR showed lower rates of normal systolic/diastolic BP values (166 (47%) vs. 254 (57%); P = 0.003) compared to controls. They also received higher stent number (1.40±0.74 vs. 1.24±0.51; P < 0.001) with higher stent length (24.3±15.6 vs. 21.7±13.9 mm; P = 0.012), and lower rate of drug-eluting stents (DESs) (210 (48%) vs. 139 (40%); P = 0.025) compared to controls. CONCLUSIONS Normal BP at the time of PCI is associated with nearly 24% risk reduction of ISR as evaluated in a new angiography in patients with coronary artery disease.

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.

Prevalence and clinical outcomes of white-coat and masked hypertension: Analysis of a large ambulatory blood pressure database

The aim of this study was to analyze prevalence and clinical outcomes of the following clinical conditions: normotension (NT; clinic BP < 140/90 mm Hg; 24‐hour BP < 130/80 mm Hg), white‐coat hypertension (WCHT; clinic BP ≥ 140 and/or ≥90 mm Hg; 24‐hour BP < 130/80 mm Hg), masked hypertension (MHT; clinic BP < 140/90 mm Hg; 24‐hour BP ≥ 130 and/or ≥80 mm Hg), and sustained hypertension (SHT; clinic BP ≥ 140 and/or ≥90 mm Hg; 24‐hour BP ≥ 130 and/or ≥80 mm Hg) in a large cohort of adult untreated individuals. Systematic research throughout the medical database of Regione Lazio (Italy) was performed to estimate incidence of myocardial infarction (MI), stroke, and hospitalizations for HT and heart failure (HF). Among a total study sample of 2209 outpatients, 377 (17.1%) had NT, 351 (15.9%) had WCHT, 149 (6.7%) had MHT, and 1332 had (60.3%) SHT. During an average follow‐up of 120.1 ± 73.9 months, WCHT was associated with increased risk of hospitalization for HT (OR 95% CI: 1.927 [1.233‐3.013]; P = .04) and HF (OR 95% CI: 3.449 [1.321‐9.007]; P = .011). MHT was associated with an increased risk of MI (OR 95% CI: 5.062 [2.218‐11.550]; P < .001), hospitalization for HT (OR 95% CI: 2.553 [1.446‐4.508]; P = .001), and for HF (OR 95% CI: 4.214 [1.449‐12.249]; P = .008). These effects remained statistically significant event after corrections for confounding factors including age, BMI, gender, smoking, dyslipidaemia, diabetes, and presence of antihypertensive therapies.

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.

Role of oxidative stress in the process of vascular remodeling following coronary revascularization

Percutaneous coronary interventions (PCI), including balloon angioplasty and implantation of both bare metal and drug eluting coronary stents, are associated with risk of restenosis and in-stent thrombosis. A better understanding of signals that regulate cellular proliferation, neointimal formation and vessel wall thickening following PCI may contribute to identify novel preventive and therapeutic strategies aimed to reduce the atherosclerosis progression and the consequent vascular sequelae. Among the possible mechanisms, an increased level of reactive oxygen species (ROS) is associated with endothelial dysfunction and vascular smooth muscle cells (VSMCs) proliferation and migration involved in the post-procedural remodeling process. This review article provides an overview of the current knowledge on the contribution of increased oxidative stress to the post-procedural pathological vascular changes. We discuss the role of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide synthase, and of proteins regulating the mitochondrial function and dynamics. We will also highlight new knowledge on the atypical Fat1 cadherin that appears to play a key role in VSMCs proliferation. In fact, its induction after vascular injury serves as a physiological regulator of VSMCs growth. Specific molecular mechanisms, including Pin1- and H2S-mediated pathways, have been identified in the vascular complications of type 2 diabetic patients. The identification of novel key players may expand our perspectives and promote the development of new tools for future preventive and therapeutic strategies in order to reduce the adverse vascular remodeling following PCI. The latter represents one of the major goals in the development of innovative technologies with relevance for clinical practice.

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.