You must remember this, A kiss is just a kiss, A sigh is just a sigh, The fundamental things apply, As time goes by.-"As Time Goes By," by Herman Hupfeld, Casablanca (1942) 1 T he increasing prevalence of older-age people in our society represents the culmination of centuries of medical, scientific, and social endeavors. At least in Western society, now relatively freed from pestilence, abject poverty, gross malnutrition, and polluted water and food sources, an increasing proportion of the population can expect to make it to old age. However, although US age-adjusted death rates from cardiovascular disease, coronary heart disease, and stroke continue to fall, a disproportionate number of people who reach old age (Ϸ80% of people aged Ն80 years) suffer from these diseases. 1a In this 2-part review, we consider important pathobiological changes that occur with aging in the cardiovascular system, exploring promising areas of recent scientific progress and novel insights that may be translatable into targeted clinical strategies to help to alleviate the excess morbidity and mortality imposed by cardiovascular disease in the elderly. In this second installment, we focus specifically on vascular disease states of the elderly, including systolic hypertension, vascular calcification, and dementia, and we review relevant basic and clinical discoveries that further elucidate these conditions. Hardening of the Arteries: Calcification, Glycosylation, and the Vasculature in Old Age The Elderly Vascular PhenotypeAging is associated with various changes in the vascular system at differing structural and functional levels. At the macroscopic level, an increase in arterial lumen size and arterial wall thickening, mainly of the intima, are observed. 2 In addition, increased vascular calcification and a generalized stiffening of the arterial tree lead to increased arterial wave reflectance, increased systolic blood pressure, decreased diastolic blood pressure, and a widened pulse pressure.An interesting aspect of vascular biology in which significant inroads have been made is our understanding of pulse wave velocity, which is partly a consequence and partly a cause of the elderly vascular phenotype. In the healthy human arterial tree, the arterial pulse wave is reflected back toward the heart from branch points and other structures in the peripheral circulation, with the reflected wave arriving back at the aortic root during diastole. In older people, the stiffening of the vasculature results in higher forward and reflected pulse wave velocities, with the reflected wave arriving back at the aortic root in late systole, leading to an augmentation of the late systolic pressure (Figure 1). 3 This age-related shift of the reflected wave from diastole into late systole leads to an increased systolic workload for the heart, decreased coronary perfusion during diastole, and the transmission of higher pressures to end organs such as the brain and kidneys. 3 Therefore, stiffening of the vasculature is directly implicated in ventricula...

Longevity is a vascular question, which has been well expressed in the axiom that man is only as old as his arteries. To a majority of men death comes primarilyn 2030, when all of the baby boomer generation will be Ն65 years of age, nearly 1 in 5 US residents is expected to be Ͼ65 years of age. By 2050, this age group is projected to more than double in number, from 38.7 million in 2008 to an estimated 88.5 million (Figure 1). 2 Similarly, the population Ն85 years of age is expected to more than triple, from 5.4 million in 2008 to 19 million by 2050. 2 With this aging of the population, the number of people at risk for adverse cardiovascular events, in particular atherothrombosis, stroke, myocardial infarction, and heart failure, will increase dramatically. The importance of these projections is underscored by the fact that currently, although octogenarians represent only 5% of the US population, they account for 20% of all hospitalizations for myocardial infarction and 30% of all myocardial infarction-related deaths. 3 A Looming Aging EpidemicDespite their increased risk of adverse cardiac events, elderly patients are less likely to receive appropriate therapy. This paradox is perhaps related to the fact that elderly patients with cardiovascular disease are more likely to be frail. 4 Heightened concerns that frail older patients may be more susceptible to adverse side effects, particularly in the setting of complex pharmacotherapy, can lead to efficacious therapies being withheld. [5][6][7] As an example, although the relative risk reduction of cholesterol-lowering therapy may be equivalent in the young and elderly, the absolute risk reduction, or number of adverse cardiovascular events prevented, may be significantly greater in elderly patients. 8 This serves as a sobering reminder that even though many exciting advances that might help fight the ravages of old age appear to be at the point of clinical translation, at the present time, clinicians must remain vigilant to ensure the delivery of best medical care to all elderly patients.In this 2-part review, we discuss important pathobiological changes that occur with aging in the cardiovascular system and how they relate to clinical outcomes. Furthermore, we explore areas of scientific progress that may, optimistically, be translatable into targeted clinical strategies to help offset the looming impact of the aging epidemic on morbidity, mortality, and healthcare resource use. Readers should be aware that we do not propose to exhaustively discuss all potential biological players in this complex arena. Rather, we will attempt to selectively highlight novel and important broad aspects of basic and cellular biology and clinical medicine that are of significant relevance to this field. In this first installment, we focus at the basic-science level on key advances in our understanding of the cellular aging process and look to extend these observations to the aging adult vasculature. Telomere Shortening and Cellular Senescence Mechanisms of Telomere-Telomerase Fun...

Aims Mounting data support a ‘calcification paradox’, whereby reduced bone mineral density is associated with increased vascular calcification. Furthermore, reduced bone mineral density is prevalent in older persons with lower body mass index (BMI). Therefore, although BMI and coronary artery calcification (CAC) exhibit a positive relationship in younger persons, it is predicted that in older persons and/or those at risk for osteoporosis, an inverse relationship between BMI and CAC may apply. We sought to explore this hypothesis in a large group of patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Methods and Results We accessed our single-center registry for 07/01/1999 to 06/30/2009, extracting data on all patients that underwent PCI. To minimize bias we excluded those at the extremes of age or BMI and non-Black/Hispanic/Caucasians, leaving 9,993 study subjects (age 66.6±9.9 years). Index lesion calcification (ILC) was analyzed with respect to BMI. Comparing index lesions with no angiographic calcification to those with the most severe, mean BMI decreased by 1.11 kg.m−2; a reduction of 3.9% (P<0.0001). By multivariable modeling, BMI was an independent inverse predictor of moderate-severe ILC (m-sILC; Odds Ratio [OR] 0.967, 95%CI 0.953–0.980, P<0.0001). Additional fully adjusted models identified that, compared to those with normal BMI, obese patients had an OR of 0.702 for m-sILC (95%CI 0.596–0.827, P<0.0001). Conclusions In a large group of PCI patients, we identified an inverse correlation between BMI and index lesion calcification. These associations are consistent with established paradigms and suggest a complex interrelationship between BMI, body size and vascular calcification.

BackgroundWhereas there are numerous studies on unintentional weight loss (UWL), these have been limited by small sample sizes, short or variable follow‐up, and focus on older patients. Although some case series have revealed that malignancies escaping early detection and uncovered subsequently are exceptional, reported follow-ups have been too short or unspecified and necropsies seldom made. Our objective was to examine the etiologies, characteristics, and long-term outcome of UWL in a large cohort of outpatients.MethodsWe prospectively enrolled patients referred to an outpatient diagnosis unit for evaluation of UWL as a dominant or isolated feature of disease. Eligible patients underwent a standard baseline evaluation with laboratory tests and chest X-ray. Patients without identifiable causes 6 months after presentation underwent a systematic follow-up lasting for 60 further months. Subjects aged ≥65 years without initially recognizable causes underwent an oral cavity examination, a videofluoroscopy or swallowing study, and a depression and cognitive assessment.ResultsOverall, 2677 patients (mean age, 64.4 [14.7] years; 51% males) were included. Predominant etiologies were digestive organic disorders (nonmalignant in 17% and malignant in 16%). Psychosocial disorders explained 16% of cases. Oral disorders were second to nonhematologic malignancies as cause of UWL in patients aged ≥65 years. Although 375 (14%) patients were initially diagnosed with unexplained UWL, malignancies were detected in only 19 (5%) within the first 28 months after referral. Diagnosis was established at autopsy in 14 cases.ConclusionThis investigation provides new information on the relevance of follow-up in the long-term clinical outcome of patients with unexplained UWL and on the role of age on this entity. Although unexplained UWL seldom constitutes a short-term medical alert, malignancies may be undetectable until death. Therefore, these patients should be followed up regularly (eg yearly visits) for longer than reported periods, and autopsies pursued when facing unsolved deaths.