According to the US National Health and Nutrition Examination Survey 2007–2010, approximately 21 % of men and 10 % of women aged 60–79 years have coronary artery disease, whereas over the age of 80, prevalence figures are close to 35 and 19 %, respectively [1]. In strata defined on the basis of gender and race, incidence varies between 4 and 14 per 1000 p-y in the 65–74 years age range and between 9 and 19 per 1000 p-y in the following decade [1].

Temporal trends show that in the US hospital, discharges for coronary artery disease, after a slow increase from 1970 to 2000, are progressively declining thereafter at a faster pace, so that 2010 values are close to those recorded in 1970 [1]. With an acceptable degree of approximation, this trend is considered to reflect changes in the incidence of the condition.

Degenerative aortic valve stenosis is nowadays the most common heart valve disease of surgical interest: it is estimated that approximately 50 % of patients with severe aortic stenosis are referred for cardiothoracic surgery [1]. Occurrence of aortic stenosis consistently increases with age: in a population-based report from Norway, prevalence figures were 1.3 % in the 60–69-year cohort, 3.9 % in the 70–79-year cohort and 9.8 % in the 80–89-year cohort. Incidence rate was 4.9‰/year and average annual increase in mean transvalvular gradient 3.2 mmHg [10]. Prevalence values were similar in a more recent population-based report, conducted in Iceland with a combination of echocardiography and CT scan-detected aortic valve calcium [11].

In Scotland, age-gender-adjusted temporal trends of hospitalisations for aortic stenosis showed a dramatic increase, from 246 cases per one million population in 1997 to 365 per one million population in 2005 [12]. Remarkably different trends have been observed in Sweden: across a 20-year interval, the unadjusted incidence of aortic stenosis remained stable, whereas its age-adjusted incidence declined. Furthermore, in spite of a 4-year increase of median age at diagnosis, mortality declined markedly, similar to the trends reported, in the same and in other studies, for heart failure and acute myocardial infarction [13]. These findings suggest that degenerative aortic stenosis shares with other largely prevalent CVD a set of modifiable risk factors, whose intensive treatment can efficaciously prevent this common valvular disease, as well as coronary artery disease.

Atrial fibrillation is the most frequent tachyarrhythmia of late life. Its incidence increases markedly with advancing age, from less than one per 1000 p-y below the age of 60 years to 25.6 per 1000 p-y in men and 23.4 in women over the age of 80 years, respectively; these values remained steady from 2000 to 2010 [14]. Prevalence of the arrhythmia in persons aged 65+ years is around 5 %; age-related trends are similar to those reported for incidence, from 4.3 % in subjects aged 66–69 years to 5.4 % above the age of 90 [15]. Long-term recordings of spontaneous heart rhythm by pacemakers and defibrillators have shown that episodes of clinically unrecognised atrial fibrillation are frequent in individuals with no documented history of the arrhythmia and may be responsible for thromboembolism [16].

Atrial fibrillation is associated with diminished survival at any age, although this excess risk is limited to the first 6 months after the diagnosis in individuals in their 80s, whereas in subjects aged 60–69 years it extends over 4 years [14]. Besides being a recognised risk factor for stroke [17], atrial fibrillation, either prevalent or incident, is associated with a 1.5–2-fold greater incidence of dementia [18], independent of stroke occurrence. Dementia is one of the most worrisome conditions associated with ageing, and its prevalence will continue to escalate in industrialised countries [19], and interventions to contrast this epidemic are eagerly searched. Thus, investigating whether optimal treatment of atrial fibrillation can prevent or postpone dementia would be a major contribution of cardiovascular medicine to healthy ageing.

Prevalence of heart failure is 5–6 % in subjects aged 60–79 years and increases to 9–12 % in those 80+ years old [1], with good consistency across different studies [20, 21]. In the Framingham Heart Study, incidence increased from 9.2 to 4.7 per 1000 p-y in men and women aged 65–74 years to 41.9 and 32.7 per 1000 p-y after the age of 85 [22], whereas greater incidence figures have been reported in the Cardiovascular Heart Study [23]. At the age of 80, the remaining lifetime risk for onset of heart failure is still a remarkable 20 % [22].

As the common final pathway of most CVD, heart failure can be expected to become increasingly common, due to the combined effect of advancing age of the population and decreasing mortality from age-related, previously highly fatal conditions, such as acute myocardial infarction. However, recent data do not fully support this expectation. In a study from Denmark, Schmidt et al. [24] reported that, from 1983 through 2013, the rate of first-time hospitalisation for heart failure increased slightly, by an average of 1 % per year, initially through 2000, and declined markedly thereafter, by 3.5 % per year. Among heart failure patients, the proportion of those aged 80+ years increased from 34 to 44 % between 1983 and 2007 and declined to 42 % in subsequent years; conversely, a threefold increase in the proportion of patients with more severe comorbidity, from 5 to 16 %, was recorded throughout the entire study period. In spite of the more advanced age and increasing complexity, 5-year mortality rate declined, by more than 40 % overall, across the 30-year period; this decline occurred for all age, sex, comorbidity and risk status patient groups [24].

Comorbidity is the presence of one or more additional disorders (or diseases) co-occurring with a primary disease or disorder, or the effect of such additional disorders or diseases [28]. Unlike complications, it does not have any aetiologic relationship with primary diagnosis. More recently, the concept of multimorbidity has been introduced in medical literature, as the co-occurrence of two or more chronic medical conditions in one person [29], irrespective of any index disease. Multimorbidity describes better what is commonly observed in older persons, when clinicians cannot identify any dominant disease and must deal with several coexisting conditions at the same time [30]. More than half of the persons aged 75+ years have at least three coexisting chronic diseases [27, 30, 31]; possibly because of more severe multimorbidity, women spend a longer part than men of their life as disabled [32].

Multimorbidity has a major role in public health, as it is responsible for escalating health-care costs; yet, it is also important for the practising physician, because it strongly influences the diagnostic process, the therapeutic approach, the effect of treatment and ultimately the patient’s outcome, in particular increasing the risk of functional decline and mortality in older persons. For example, multimorbidity confounds the diagnostic process, because it favours atypical presentations of diseases: delirium often heralds dementia, but it may represent the onset of several clinical conditions, including acute heart failure or myocardial infarction. Multimorbidity complicates treatment, because most randomised trials that represent the foundation of evidence-based guidelines enrolled young patients free of significant associated diseases [33]. Paradoxically, rigorous application of disease-specific guidelines in typical geriatric patients may have serious adverse effects [34], mostly mediated by polypharmacy. Indeed, the risk and severity of adverse drug reactions and of drug-drug interactions increase with the number of prescriptions [35], so that polypharmacy may represent an independent risk factor for death [36]. On the other hand, abstention from appropriate therapies is also very common in complex older persons with multimorbidity and may negatively affect survival, as observed after acute myocardial infarction [37].

Several approaches have been proposed to quantify comorbidity and multimorbidity, usually based on clinical appraisal of the presence or severity of diseases [31, 38]. A simple count of chronic coexisting diseases has good predictive ability against important outcomes such as death or incident disability, although better results are provided by measures that also score disease severity, such as the Charlson Comorbidity Index [39] or the Index of Coexistent Diseases [40]. The Cumulative Illness Rating Scale (CIRS) [41] is another very popular instrument to weigh the severity of comorbidity: in spite of its large diffusion, it should be considered as suboptimal, because it considers the functional impact of a disease to measure its severity, therefore preventing any independent assessment of the association between a given chronic disease and functional status. Analysis of therapeutic patterns offers an alternative approach to measuring comorbidity and multimorbidity [42], although its reliability and validity are lower than with clinical methods [31, 38].

Functional status is a major determinant of health status and prognosis of older persons. In cardiac patients, clear evidence for this has been offered by a large study of older persons hospitalised for heart failure, whose 30-day and 5-year prognosis was strongly predicted by the presence of dementia and mobility limitations, adjusting for the severity of the underlying cardiac condition [43].

Evaluation of functional status is an essential component of comprehensive geriatric assessment, the specific technology that geriatrics applies to identify and, possibly, correct the variety of problems an older person may have [44, 45]. Traditional measures of functional status are represented by Katz’s activities of daily living (ADL) [46], which evaluate the ability of an older person to manage basic tasks (bathing, dressing, transferring, using the toilet, maintaining continence and feeding) essential for indoor independence, and Lawton’s instrumental activities of daily living (IADL) [47], exploring higher-level abilities (using public transportations and telephone, managing finances and drug therapy, housekeeping, shopping and preparing meals), which consent outdoor independence and social life. Consistently in most studies, approximately 10 % of persons aged 65+ and one-third of those aged 80+ are found to have ADL disability and, therefore, depend on somebody’s help for their primary needs. Conversely, the prevalence of IADL disability is more variable across different settings, because IADL tasks are more sensitive to the social and cultural context.

These tools were initially proposed to standardise the process of evaluating the needs an older person might have and identifying the most appropriate level or setting of care. They were subsequently applied also to guide rehabilitation. However, with time it became clear that the level of disability represents a summary measure of the combined effect of “normal” ageing, multimorbidity, changes in cognition and mood on an older person’s global health; therefore, measuring disability improves prognostic assessment, independent of specific clinical diagnoses [48].

The relationship between coexisting diseases and functional status is complex. On one hand, multimorbidity strongly increases the risk of disability, proportionately to the number and severity of coexisting diseases [31]. On the other hand, specific associations of diseases may synergistically compromise functional autonomy: for example, chronic heart failure and previous stroke combined increase the risk of disability in excess of what can be anticipated from a simple summation of the risks associated with each individual condition [49]. Therefore, functional evaluation has gained a remarkable role within comprehensive geriatric assessment, because it conveys relevant information across the entire spectrum of conditions an older person may present, within all care settings. Mostly, functional evaluation is essential to identifying frailty.

Approximately one-third of older persons are robust, i.e. have no major diseases and free of IADL disability; on the other end, about 10 % of persons aged 70+ years have an unsteady health status, characterised by multimorbidity and a rapid deterioration of physical and cognitive abilities following apparently trivial injuries. Geriatric literature identifies these subjects as “frail” [50]. Disability and frailty must be considered as two distinct, though correlated, conditions, with similar epidemiology (age-related prevalence) and multifactorial pathophysiology. There is a general consensus that frailty represents an expression of reduced functional reserve, with impairment of mechanisms of biological homeostasis, leading to extreme vulnerability to stressors, such as an acute disease or environmental changes. As a consequence, frailty can be better identified from the assessment of complex, integrated functions and application of stimuli that challenge one’s physiological reserves. The most convincing example is probably the reduction in gait speed: albeit it is observed as a universal age-related phenomenon, it occurs with a wide range of variability across individuals depending on several factors, and it is magnified in the presence of a precarious health status. Because walking is a very complex activity, slowing gait may depend on abnormalities in central or peripheral nervous system, impaired cardiopulmonary efficiency or muscular-skeletal problems. No matter how complex its pathophysiology is, in order to operationalise frailty, it is important to have measures easy to detect and strongly associated with global health status: gait speed has all these features, and its decrease is a formidable predictor of death and disability in the elderly, both in the general population [51] and in clinical settings [52].

Using data from the Cardiovascular Health Study, Fried et al. developed a model coherent with this conceptualisation of frailty and easy to operationalise [50]. According to this model, frailty is characterised by the presence of at least three of the following five measurable conditions: muscle weakness, unintentional weight loss, reduced walking speed, reduced level of habitual physical activity and fatigue (Table 2.1). More recently, the concept of sarcopenia (age-related loss of skeletal muscle mass and strength) [53] has gained popularity as an important determinant of health status in older persons, combined with frailty. Together, these conditions may indeed lead to reduced energy production and limitation in functional activities, such as walking: this has been shown in the InCHIANTI epidemiological study on community-dwelling older persons, in whom poor nutrient intake and decreased muscle mass were associated with frailty and had negative health effects [54].

In agreement with Fried’s model [50], acute and chronic diseases may favour the onset of frailty by either reducing functional reserves or as stressors that unmask previously compensated deficits. The need for tapping into functional reserves for too long or too extensively may precipitate frail older persons into disability: it should be emphasised that, unlike other models of frailty, within Fried’s model disability would represent a possible consequence of frailty rather than one of its determinants.