SUMMARY: Introduction: The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age‐related development of a prothrombotic imbalance in the fibrinolysis homeostasis has been hypothesized as the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the result of the interactions among multiple plasminogen activators and inhibitors constituting the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Methods: Narrative review. Results: Plasminogen activator inhibitor‐1 (PAI‐1) is a member of the superfamily of serine‐protease inhibitors (or serpins), and the principal inhibitor of both the tissue‐type and the urokinase‐type plasminogen activator, the two plasminogen activators able to activate plasminogen. Current evidence describing the central role played by PAI‐1 in a number of age‐related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Conclusions: Despite some controversial and unclear issues, PAI‐1 represents an extremely promising marker that may become a biological parameter to be progressively considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age‐related conditions in the future.

Aging is known to be associated with an increased prevalence of multiple chronic diseases, which frequently causes the use of complex therapeutic regimens. The aging process is characterized by relevant changes in drug handling, physiological reserve, and pharmacodynamic response. Hepatic drug clearance of several drugs decreases with aging, mainly due to reduced blood flow, and hepatocyte mass. Renal function also declines with aging, mainly due to sclerotic changes in the glomeruli. Furthermore, due to reduced muscle mass, older subjects frequently have depressed glomerular filtration rate despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly the clearance of hydrosoluble drugs. Changes in pharmacodynamics are also well documented in the cardiovascular and nervous system. Age-related changes in pharmacokinetics and pharmacodynamics, together with comorbidity and polypharmacy, make elderly patients at special risk for advers drug reactions, which in turn are cause of relevant health burden and costs. Selected measures can assist in preventing or detecting timely such adverse events.

The aim of this study was to assess the prognostic role of co-morbidity in severe chronic obstructive pulmonary disease (COPD). A cohort of 270 COPD patients, mean (+/-SD) age 67+/-9 yrs, consecutively discharged from a University Hospital after an acute exacerbation was studied. Mean (+/-SD) forced expiratory volume in one second (FEV1) was 34+/-16% of predicted and FEV1/forced vital capacity (FVC) was 40.5+/-13.8%. The most common co-morbid diseases were: hypertension (28%), diabetes mellitus (14%), and ischaemic heart disease (10%). Clinical, electrocardiogram (ECG), and respiratory function data taken at the time of discharge were collected from the clinical records. The Charlson's index was used to quantify co-morbidity. Follow-up was conducted by means of telephone calls. Multivariate survival analysis was used to identify the independent predictors of death. The median survival of the cohort was 3.1 yrs. Death was predicted by the following variables: age (hazard rate (HR) 1.04; 95% confidence intervals (95% CI) 1.02-1.05), ECG signs of right ventricular hypertrophy (HR 1.76; 95% CI 1.30-2.38), chronic renal failure (HR 1.79; 95% CI 1.05-3.02), ECG signs of myocardial infarction or ischaemia (HR 1.42; 95% CI 1.02-1.96), FEV1 < 590 mL (HR 1.49; 95% CI 0.97-2.27). A score based upon these variables predicted mortality at 5 yrs with a sensitivity of 63% and a specificity of 77%. Selected co-morbid diseases and electrocardiogram signs of right ventricular hypertrophy play a major prognostic role in advanced chronic obstructive pulmonary disease. The clinical assessment of patients with chronic obstructive pulmonary disease should include these important and easily measurable variables.

In order to characterize the neuropsychologic profile of patients with hypoxic-hypercapnic chronic obstructive pulmonary disease (COPD), the performance of 36 patients with COPD 69 ± 10 yr of age (mean ± SD) on 19 tests exploring eight cognitive domains was compared with those of 29 normal adults (69 ± 7 yr of age), 20 normal elderly adults (78 ± 2 yr of age), 26 patients with Alzheimer-type dementia (72 ± 6 yr of age), and 28 with multiinfarct dementia (MID) (70 ± 8 yr of age). The discriminant analysis of cognitive test scores showed that 48.5% of patients with COPD had a specific pattern of cognitive deterioration characterized by a dramatic impairment in verbal and verbal memory tasks, well-preserved visual attention, and diffuse worsening of the other functions. The remaining patients with COPD were functionally classified as normal adults (12.1%), normal elderly adults (15.2%), those with MID (12.1%), and those with Alzheimer-type dementia (12.1%) according to discriminant analysis. Cognitive impairment was significantly and positively correlated with age (p < 0.05) and duration of hypoxic-hypercapnic chronic respiratory failure (p < 0.05). Because patients with COPD were receiving oxygen therapy from the beginning of oxyhemoglobin desaturation, results suggest that continuous oxygen therapy does not prevent or only partly prevents cognitive decline in COPD. Although some analogies between age-related and COPD-related cognitive decline are evident, a distinct cognitive profile was found in a large fraction of patients with COPD and it differs in several aspects from those of both normal and demented subjects.