Gianluca Testa

Cognitive impairment and cardiovascular diseases in the elderly. A heart–brain continuum hypothesis

The aging population is increasing and, therefore, a higher prevalence of cardiac disease is emerging; including hypertension, coronary artery disease, atrial fibrillation and chronic heart failure. Large cohort studies have revealed a relationship among increased risk for cognitive impairment and dementia in cardiovascular diseases probably due to embolic stroke or chronic cerebral hypoperfusion. Thus, the aim of the present review is to overview the studies that investigate the presence and/or the development of cognitive impairments and dementia in patients with varied types of cardiovascular disease. Finally, a continuum among hypertension, coronary artery disease, atrial fibrillation and chronic heart failure with to the development of cognitive impairment and progression to dementia has been hypothesized.

Moderate alcohol consumption predicts long-term mortality in elderly subjects with chronic heart failure

ObjectiveModerate alcohol consumption is related to a reduction of mortality. However, this phenomenon is not well established in the elderly, especially in the presence of chronic heart failure (CHF). The aim of the study was to verify the effect of moderate alcohol consumption on 12-year mortality in elderly community-dwelling with and without CHF.Settingscommunity-dwelling from 5 regions of Italy.ParticipantsA cohort of 1332 subjects aged 65 and older.MeasurementMortality after 12-year follow-up in elderly subjects (≥65 years old) with and without CHF was studied. Moderate alcohol consumption was considered ≤250 ml/day (drinkers).ResultsIn the absence of CHF (n=947), mortality was 42.2% in drinkers vs. 53.7% in non-drinker elderly subjects (p=0.021). In contrast, in the presence of CHF (n=117), mortality was 86.5% in drinkers vs. 69.7% in non-drinker elderly subjects (p=0.004). Accordingly, Cox regression analysis shows that a moderate alcohol consumption is protective of mortality in the absence (HR=0.79; CI 95% 0.66–0.95; p<0.01) but it is predictive of mortality in the presence of CHF (HR=1.29; CI 95% 1.05–1.97; p<0.05).ConclusionsOur data demonstrates that moderate alcohol consumption is associated with an increased long-term mortality risk in the elderly in the presence of CHF.

Biomarkers in sarcopenia: A multifactorial approach

The slow and continuous loss of muscle mass that progresses with aging is defined as sarcopenia. Sarcopenia represents an important public health problem, being closely linked to a condition of frailty and, therefore, of disability. According to the European Working Group on Sarcopenia in Older People, the diagnosis of sarcopenia requires the presence of low muscle mass, along with either low grip strength or low physical performance. However, age-related changes in skeletal muscle can be largely attributed to the complex interactions among factors including alterations of the neuromuscular junction, endocrine system, growth factors, and muscle proteins turnover, behavior-related and disease-related factors. Accordingly, the identification of a single biomarker of sarcopenia is unreliable, due to its multifactorial pathogenesis with the involvement of a multitude of pathways. Thus, in order to characterize pathophysiological mechanisms and to make a correct assessment of elderly patient with sarcopenia, a panel of biomarkers of all pathways involved should be assessed.

Chronic obstructive pulmonary disease and long-term mortality in elderly subjects with chronic heart failure

BackgroundChronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are associated with high rates of mortality in elderly subjects. Concurrent CHF and COPD frequently occur, especially in with advancing age. This study examines long-term mortality in community-dwelling elderly subjects affected by CHF alone, COPD alone, and coexistent CHF and COPD.MethodsThe study evaluated 12-years mortality in 1288 subjects stratified for the presence or absence of CHF or COPD alone, and for coexistence of CHF and COPD.ResultsMortality, at 12xa0year follow-up, was 46.7% overall, 68.6% in the presence of CHF alone (pu2009<u20090.001), 56.9% in the presence of COPD alone (pu2009<u20090.01); mortality was 86.2% where CHF and COPD coexisted (pu2009<u20090.001) and was significantly higher than in CHF or COPD alone (pu2009<u20090.05). Multivariate analysis indicates that CHF (Hazard risku2009=u20091.67, 95% confidence interval 1.15–3.27, pu2009<u20090.031) and COPD (Hazard risku2009=u20091.27, 95% confidence intervalu2009=u20091.08–1.85, pu2009<u20090.042) were predictive of long-term mortality. When CHF and COPD simultaneously occurred, the risk dramatically increased up to 3.73 (95% confidence intervalu2009=u20091.19–6.93, pu2009<u20090.001).ConclusionsLong-term follow-up showed higher mortality among elderly subjects affected by CHF or COPD. Simultaneous presence of CHF and COPD significantly increased the risk of death. Therefore, the presence of COPD in CHF patients should be considered a relevant factor in predicting high risk of mortality.

Prognostic role of lactate on mortality in younger and older patients with cardio-respiratory failure admitted to an acute intensive care unit

Background and aimAcidosis is able to induce negative changes of different organs that increase progressively with aging. At present it is not known whether the levels of lactate may differently influence the prognosis of younger and older patients. Thus, the aim of this study is to evaluate the prognostic value of lactate levels after admission of younger and older patients to an acute intensive care unit.MethodsYounger (<65xa0years, nxa0=xa0118) and older (≥65xa0years, nxa0=xa0165) patients admitted to an acute intensive care unit were prospectively enrolled and classified according to diagnosis of acute heart or/and respiratory failure. For each patient, APACHE II score, time of hospitalization and mortality, blood levels of lactate were collected.ResultsBoth in-hospital mortality and lactatexa0>2.5xa0mmol/L at the admission was higher in the older than in the younger patients (42.4 vs. 20.3xa0%, pxa0<xa00.01 and 57.8 vs. 31.9xa0%, pxa0<xa00.01, respectively). Lactate level was higher in older than in the younger patients both at admission and after 24xa0h (3.9xa0±xa03.4 vs. 2.4xa0±xa02.2xa0mmol/L and 2.4xa0±xa02.0 vs. 1.4xa0±xa01.3xa0mmol, pxa0<xa00.01, respectively). Accordingly, multivariate analysis shows that lactate was predictive of mortality in younger (ORxa0=xa02.65, 95xa0% CI 1.62–5.24, pxa0=xa00.03) and even more in the older (ORxa0=xa04.74, 95xa0% CI 2.10–6.70, pxa0<xa00.01) patients.ConclusionsLactate concentration increase is associated with increased mortality in younger patients but, even more so, in older patients admitted to an acute intensive care unit. These results confirm the experimental evidence showing acidosis has a greater effect of leading to organ failure and higher mortality with increasing age.

Implications of Cellular Aging in Cardiac Reprogramming

Aging is characterized by a chronic functional decline of organ systems which leads to tissue dysfunction over time, representing a risk factor for diseases development, including cardiovascular. The aging process occurring in the cardiovascular system involves heart and vessels at molecular and cellular level, with subsequent structural modifications and functional impairment. Several modifications involved in the aging process can be ascribed to cellular senescence, a biological response that limits the proliferation of damaged cells. In physiological conditions, the mechanism of cellular senescence is involved in regulation of tissue homeostasis, remodeling, and repair. However, in some conditions senescence-driven tissue repair may fail, leading to the tissue accumulation of senescent cells which in turn may contribute to tumor promotion, aging, and age-related diseases. Cellular reprogramming processes can reverse several age-associated cell features, such as telomere length, DNA methylation, histone modifications and cell-cycle arrest. As such, induced Pluripotent Stem Cells (iPSCs) can provide models of progeroid and physiologically aged cells to gain insight into the pathogenesis of such conditions, to drive the development of new therapies for premature aging and to further explore the possibility of rejuvenating aged cells. An emerging picture is that the tissue remodeling role of cellular senescence could also be crucial for the outcomes of in vivo reprogramming processes. Experimental evidence has demonstrated that, on one hand, senescence represents a cell-autonomous barrier for a cell candidate to reprogramming, but, on the other hand, it may positively sustain the reprogramming capability of surrounding cells to generate fully proficient tissues. This review fits into this conceptual framework by highlighting the most prominent concepts that characterize aging and reprogramming and discusses how the aging tissue might provide a favorable microenvironment for in vivo cardiac reprogramming.

Circulating endothelial progenitor cells biology and regenerative medicine in pulmonary vascular diseases.

Pulmonary vascular disorders (PVDs) include primary or secondary diseases who ultimately influence the right heart function. Several researches showed that stem and progenitor cells may represent a novel approach in treating pulmonary hypertension. In particular, circulating endothelial progenitor cells (EPCs) are mobilized either from the bone marrow and/or arteries to replace dysfunctional endothelial cells and restore blood perfusion to ischemic tissues. They may deliver paracrine signals to stimulate local angiogenesis or may be physically incorporated within neovessels. Understanding the molecular mechanisms utilized by vascular endothelial growth factor (VEGF) to stimulate EPC might shed light on novel targets for regenerative medicine. Ca2+ machinery regulates proliferation, migration, tube formation, and, therefore, differentiation of EPCs may give valuable insights into the biology of these cells; the Ca2+ machinery in these cells is extremely plastic and may vary depending on their origin. In this paper, we review EPCs subtypes, their sources, biological properties, functional mechanisms and of course involvement in pulmonary vascular diseases.

Corrigendum to “Tandem action of exercise training and food restriction completely preserves ischemic preconditioning in the aging heart” [Experimental Gerontology 40/1–2 (2005) 43–50]

Cattedra di Geriatria, Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Universita degli Studi di Napoli ‘Federico II’, Naples, Italy Cattedra di Medicina Interna, Dipartimento di Scienze Animali, Vegetali ed Ambientali, Universita del Molise, Campobasso, Italy Istituto Scientifico di Campoli/Telese, Fondazione Salvatore Maugeri, IRCCS, Benevento, Italy Department of Clinical Pathology and Laboratory Medicine, II University of Naples, Naples, Italy Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA