Oriana Scala

Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis.

OBJECTIVES The purpose of this paper was to assess whether statins reduce all-cause mortality and cardiovascular (CV) events in elderly people without established CV disease. BACKGROUND Because of population aging, prevention of CV disease in the elderly is relevant. In elderly patients with previous CV events, the use of statins is recommended by guidelines, whereas the benefits of these drugs in elderly subjects without previous CV events are still debated. METHODS Randomized trials comparing statins versus placebo and reporting all-cause and CV mortality, myocardial infarction (MI), stroke, and new cancer onset in elderly subjects (age ≥ 65 years) without established CV disease were included. RESULTS Eight trials enrolling 24,674 subjects (42.7% females; mean age 73.0 ± 2.9 years; mean follow up 3.5 ± 1.5 years) were included in analyses. Statins, compared with placebo, significantly reduced the risk of MI by 39.4% (relative risk [RR]: 0.606 [95% confidence interval (CI): 0.434 to 0.847]; p = 0.003) and the risk of stroke by 23.8% (RR: 0.762 [95% CI: 0.626 to 0.926]; p = 0.006). In contrast, the risk of all-cause death (RR: 0.941 [95% CI: 0.856 to 1.035]; p = 0.210) and of CV death (RR: 0.907 [95% CI: 0.686 to 1.199]; p = 0.493) were not significantly reduced. New cancer onset did not differ between statin- and placebo-treated subjects (RR: 0.989 [95% CI: 0.851 to 1.151]; p = 0.890). CONCLUSIONS In elderly subjects at high CV risk without established CV disease, statins significantly reduce the incidence of MI and stroke, but do not significantly prolong survival in the short-term.

The Prognostic Value of Normal Stress Cardiac Magnetic Resonance in Patients with Known or Suspected Coronary Artery Disease: A Meta-analysis

Background—Ischemia detection with stress cardiac magnetic resonance (CMR) is typically based on induction of either myocardial perfusion defect or wall motion abnormality. Single-center studies have shown the high value of stress CMR for risk stratification. The aim of this study was to define the prognostic value of stress CMR for prediction of adverse cardiac events in patients with known or suspected coronary artery disease. Methods and Results—Studies published between January 1985 and April 2012 were identified by database search. We included studies using stress CMR to evaluate subjects with known or suspected coronary artery disease and providing primary data on clinical outcomes of nonfatal myocardial infarction or cardiac death with a follow-up time ≥3 months. Total of 14 studies were finally included, recruiting 12 178 patients. The negative predictive value for nonfatal myocardial infarction and cardiac death of normal CMR was 98.12% (95% confidence interval, 97.26–98.83) during a weighted mean follow-up of 25.3 months, resulting in estimated event rate after a negative test equal to 1.88% (95% confidence interval, 1.17–2.74). The corresponding annualized event rate after a negative test was 1.03%. Comparable negative predictive values for major coronary events were obtained in studies considering the absence of inducible perfusion defect compared with those evaluating the absence of inducible wall motion abnormality (98.39% versus 97.31%, respectively; P=0.227 by meta-regression analysis). Conclusions—Stress CMR has a high negative predictive value for adverse cardiac events, and the absence of inducible perfusion defect or wall motion abnormality shows a similar ability to identify low-risk patients with known or suspected coronary artery disease.

Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries: A digital reactive hyperemia study

BACKGROUND To assess endothelial function (EF) in type 2 diabetic patients with angiographically normal coronaries compared to diabetic patients with obstructive coronary artery disease (CAD) and to non-diabetic patients, with and without CAD. METHODS One hundred eighty-three patients undergoing coronary angiography were divided in: group 1 with diabetes mellitus (DM) and CAD (n = 58); group 2 with DM without CAD (n = 58); group 3 with CAD without DM (n = 31) and group 4 without CAD and DM (n = 36). EF was assessed by reactive hyperemia index (RHI) using a fingertip peripheral arterial tonometry and compared to values obtained in 20 healthy volunteers. RESULTS RHI was significantly lower in patients with DM compared to patients without DM (1.69 ± 0.38 vs 1.84 ± 0.44; p = 0.019). RHI was comparable among groups 1, 2 and 3, each value being significantly lower compared to group 4 (2 ± 0.44; p<0.001 vs group 1; p<0.005 vs group 2; p<0.002 vs group 3). At multivariate analysis DM and CAD were significant predictors of endothelial dysfunction (ED) (OR = 2.29; p = 0.012; OR = 2.76; p = 0.001, respectively), whereas diabetic patients (n = 116) CAD and glycated haemoglobin (HbA1c) were independent significant predictors of ED (OR = 3.05; p = 0.009; OR = 1.96; p = 0.004, respectively). Diabetic patients with ED (n = 67) had higher levels of HbA1c than diabetic patients with normal endothelial function (7.35 ± 0.97 vs 6.87 ± 0.90; p = 0.008) and RHI inversely correlated to HbA1c (p = 0.02; r = -0.210). CONCLUSIONS Diabetic patients with and without CAD show significantly impaired peripheral vascular function compared to non-diabetic patients without CAD. ED in diabetic patients without CAD is comparable to that of patients with CAD but without DM. HbA1c is a weak independent predictor of ED.

Vascular Endothelial Growth Factor Blockade Prevents the Beneficial Effects of β-Blocker Therapy on Cardiac Function, Angiogenesis, and Remodeling in Heart Failure

Background—Impaired angiogenesis in the post-myocardial infarction heart contributes to the progression to heart failure. The inhibition of vascular endothelial growth factor (VEGF) signaling has been shown to be crucial for the transition from compensatory hypertrophy to cardiac failure. Importantly, &bgr;-adrenergic receptor blocker therapy has been also shown to improve myocardial perfusion by enhancing neoangiogenesis in the failing heart. Methods and Results—Eight weeks from surgically induced myocardial infarction, heart failure rats were randomized to receive bisoprolol (B) or vehicle. At the end of a 10-week treatment period, echocardiography revealed reduced cardiac diameters and improved cardiac function in B-treated compared with vehicle-treated rats. Moreover, B treatment was associated with increased cardiac angiogenesis and in vivo coronary perfusion and reduced cardiac fibrosis. Importantly, 2 weeks after B treatment was started, increased cardiac VEGF expression and Akt and endothelial NO synthase activation were observed by comparing B-treated with drug-untreated failing hearts. To test whether the proangiogenic effects of B act via activation of VEGF pathway, rats were intravenously injected with adenoviral vector encoding a decoy VEGF receptor (Ad-Flk) or a control adenovirus (Ad-C), at the start of the treatment with B. After 10 weeks, histological analysis revealed reduced capillary and coronary perfusion in B-treated plus Ad-Flk rats compared with B-treated plus Ad-C rats. Moreover, VEGF inhibition counteracted the positive effects of B on cardiac function and remodeling. Conclusions—&bgr;-Blockade promotes cardiac angiogenesis in heart failure via activation of VEGF signaling pathway. &bgr;-Blocker–induced enhancement of cardiac angiogenesis is essential for the favorable effects of this therapy on cardiac function and remodeling.

Coronary computed tomography: current role and future perspectives for cardiovascular risk stratification

Coronary artery disease (CAD) is the major cause of morbidity and mortality worldwide. More than 50% of CAD deaths occur in previously asymptomatic individuals at intermediate cardiovascular risk, highlighting the need of more accurate individual risk assessment to decrease cardiovascular events. Cardiac computed tomography (CCT) has emerged as a valuable technique for risk stratification in asymptomatic subjects and in symptomatic patients without known CAD. The absence of coronary artery calcium (CAC) identifies asymptomatic subjects at very low cardiac risk and is reasonable in intermediate risk individuals, in whom CAC measurement reclassifies a substantial number of subjects to different risk categories. In symptomatic patients with suspected CAD, detection of non-obstructive or obstructive CAD by CCT angiography is associated with increased all-cause mortality, and provides incremental risk stratification to CAC. Further studies are needed to assess the impact of CCT on clinical outcomes and its cost-effectiveness in different clinical settings.

Molecular aspects of the cardioprotective effect of exercise in the elderly

Aging is a well-recognized risk factor for several different forms of cardiovascular disease. However, mechanisms by which aging exerts its negative effect on outcome have been only partially clarified. Numerous evidence indicate that aging is associated with alterations of several mechanisms whose integrity confers protective action on the heart and vasculature. The present review aims to focus on the beneficial effects of exercise, which plays a pivotal role in primary and secondary prevention of cardiovascular diseases, in counteracting age-related deterioration of protective mechanisms that are crucially involved in the homeostasis of cardiovascular system. In this regard, animal and human studies indicate that exercise training is able: (1) to improve the inotropic reserve of the aging heart through restoration of cardiac β-adrenergic receptor signaling; (2) to rescue the mechanism of cardiac preconditioning and angiogenesis whose integrity has been shown to confer cardioprotection against ischemia and to improve post-myocardial infarction left ventricular remodeling; (3) to counteract age-related reduction of antioxidant systems that is associated to decreased cellular resistance to reactive oxygen species accumulation. Moreover, this review also describes the molecular effects induced by different exercise training protocols (endurance vs. resistance) in the attempt to better explain what kind of exercise strategy could be more efficacious to improve cardiovascular performance in the elderly population.

N-terminal pro-b-type natriuretic peptide and left atrial function in patients with congestive heart failure and severely reduced ejection fraction.

AIMS Amino-terminal portion of pro-B-type natriuretic peptide (NT-pro-BNP) is a valuable diagnostic and prognostic marker in congestive heart failure (CHF). In CHF patients, elevation of natriuretic peptide levels correlate with decreased left ventricular (LV) ejection fraction (EF) and increased left atrial (LA) volumes, but a correlation with LA function that is a determinant of haemodynamic and clinical status in CHF with independent prognostic value has never been investigated. Aim of this study was to evaluate the relationship between cardiac neurohormonal activation and LA function in patients with CHF due to dilated cardiomyopathy. METHODS AND RESULTS One hundred and one patients (86% males; mean age, 64 ± 11 years) with dilated ischaemic or non-ischaemic cardiomyopathy, LV EF ≤45% (mean LV EF, 33 ± 8%), and New York Heart Association class II-IV underwent transthoracic echocardiography to evaluate LA fractional active and total emptying from M- and B-Mode images, and, on the same day, venous blood sample collection to dose NT-pro-BNP. By univariate analyses, NT-pro-BNP significantly correlated to age, LA dimensions, LA function indexes, EF, and functional class. At multivariate analysis, LV EF and M- or B-Mode indexes of LA function were the only independent predictors of NT-pro-BNP values. A NT-pro-BNP cut-off of 1480 pg/mL identified LA dysfunction with 89% specificity and 54% sensitivity. CONCLUSION In CHF patients with severely impaired systolic function, NT-pro-BNP levels reflect LA and LV dysfunction. These data should prompt studies to investigate the relationship between changes of LA function and NT-pro-BNP levels and their clinical value as prognostic and therapeutic targets in CHF.

Sleep-disordered breathing, impaired cardiac adrenergic innervation and prognosis in heart failure.

Objective Unfavourable effects of sleep-disordered breathing (SDB) in heart failure (HF) are mainly mediated by impaired sympathetic activity. Few data are available on SDB and cardiac adrenergic impairment evaluated at myocardial level. The aim of the study was to assess the relationship between SDB, cardiac sympathetic innervation assessed by 123I-metaiodobenzylguanidine (123I-MIBG) imaging and prognosis in HF. Methods Observational, prospective study enrolling patients with HF and reduced systolic function. Patients underwent nocturnal cardiorespiratory monitoring to assess SDB presence by apnoea/hypopnoea index (AHI), and 123I-MIBG imaging to calculate heart-to-mediastinum (H/M) ratios and washout rate. Patients were prospectively followed for 29±18 months for the combined endpoint of cardiovascular death and HF hospitalisation. Results Ninety-four patients (66.1±9.8 years; left ventricular ejection fraction 32±7%) were enrolled; 72 (77%) showed SDB and, compared with non-SDB, significantly reduced early (1.67±0.22 vs 1.77±0.13; p=0.019) and late H/M ratios (1.50±0.22 vs 1.61±0.23; p=0.038). Dividing patients into two groups according to SDB severity, patients with a moderate–severe disturbance (AHI >15; n=43) showed significantly worse survival for the composite study outcome (log-rank test, p=0.001) with respect to patients with mild or no disorder (AHI ≤15; n=51). Adding SDB variables to the already known prognostic role of 123I-MIBG imaging, we observed a worse survival in patients with both SDB and H/M impairment. Conclusions Patients with systolic HF and SDB show more impaired cardiac adrenergic innervation assessed by 123I-MIBG imaging, and more adverse prognosis compared with HF patients without SDB.

EFFECTS OF SLEEP APNEA ON CARDIAC SYMPATHETIC ACTIVITY IN PATIENTS WITH SEVERE SYSTOLIC HEART FAILURE: A 123MIBG SCINTIGRAPHIC STUDY

Sleep apnea (SA) has been reported to worsen prognosis in patients with heart failure, likely through enhanced sympathetic drive arising from nocturnal arousals. However, very few studies have evaluated the association between SA and cardiac sympathetic innervation in heart failure patients. We