Cardiovascular & Haematological Disorders - Drug Targets - Volume 11, Issue 1, 2011

In developed and developing countries, the population of very old people (more than 80 years) is expected to increase over the coming decades. By 2050, there will be an estimated 56.9 million nonagenarians worldwide, an 800% increase compared with today. In this group, the prevalence and incidence of stroke is very high, with great impact on morbidity and mortality. Only 10% of survivors may expect desirable recovery, and over 50% results with severe disability, the majority of them requiring in-home geriatric care or admittance to nursing homes. In spite of this, clinical trials that investigate acute management and primary and secondary prevention drugs are scarce in this population because most of the main trials excluded patients over 80 years. Results in young patients can not be extrapolated. In the elderly population, decrease in hepatic and renal function, metabolic pathways disturbances, polypharmacy and cognitive decline affects the efficacy, safety and adherence to long-term treatments. In this issue of the journal, we will review the evidence of acute treatment (intravenous thrombolysis) in the reduction of the functional impact of ischemic events in the very old. We will also evaluate the different therapies (antihypertensive and hypolipidemic drugs) in primary and secondary prevention and discuss the management of desired blood pressure levels. We will analyze the safety, efficacy and tolerability of statin therapy in this special group. A deeper understanding of the characteristics of aged patients would facilitate a better management of their cerebrovascular events.

In developed and developing countries, the population of very old people (more than 80 years) is expected to increase over the coming decades. By 2050, there will be an estimated 56.9 million nonagenarians worldwide, an 800% increase compared with today. In this group, the prevalence and incidence of stroke is very high, with great impact on morbidity and mortality. Only 10% of survivors may expect desirable recovery, and over 50% results with severe disability, the majority of them requiring in-home geriatric care or admittance to nursing homes. In spite of this, clinical trials that investigate acute management and primary and secondary prevention drugs are scarce in this population because most of the main trials excluded patients over 80 years. Results in young patients can not be extrapolated. In the elderly population, decrease in hepatic and renal function, metabolic pathways disturbances, polypharmacy and cognitive decline affects the efficacy, safety and adherence to long-term treatments. In this issue of the journal, we will review the evidence of acute treatment (intravenous thrombolysis) in the reduction of the functional impact of ischemic events in the very old. We will also evaluate the different therapies (antihypertensive and hypolipidemic drugs) in primary and secondary prevention and discuss the management of desired blood pressure levels. We will analyze the safety, efficacy and tolerability of statin therapy in this special group. A deeper understanding of the characteristics of aged patients would facilitate a better management of their cerebrovascular events.

In our analysis, patients who were treated with intravenous rt-PA had a better outcome than untreated patients, and this effect was not dependent on age. The weight of evidence to date indicates a potential for benefit in older people, and there is no a priori reason to suspect a diminished effect when compared with younger people. The risk of bleeding is similar in both groups. We believe that clinical treatment guidelines should be revised in order to remove the age restriction in the use of intravenous rt-PA acute ischemic stroke.

The aging population is an undeniable reality which must be faced by all health systems all over the world. Among people over 80 years old, increase in stroke incidence, high mortality rates and adverse outcomes are problems of major public concern. Lack of evidence-based data to guide rational decision making on vascular risk factors management to avoid recurrence in elderly stroke patients increases the areas of uncertainty, and sometimes favors medical inertia at the time of taking care of this growing elderly population.

As population grows old, the number of persons at risk of cardiovascular events also grows. Though octogenarians form a small percentage of the general population their absolute risk of coronary and cerebrovascular disease is high, but there is still some doubt as to whether high plasma cholesterol levels increase vascular risk in this age group, as published data are conflicting. There is evidence that elevated plasma cholesterol increases the risk of coronary artery disease in older adults, and an inverse linear relationship was found between HDL cholesterol levels and the risk of mortality from ischemic heart disease in all age groups. The relationship between total plasma cholesterol and the risk of death from ischemic stroke is weak in younger populations and is even lower in people between 70 and 89 years, and is inverse for hemorrhagic stroke. However, studies showed that statin treatment lowers the risk of ischemic stroke, independently of age. Statins are underused in the elderly, perhaps because of lack of perception of the real vascular risk of older adults, concerns about statin efficacy or safety in this population, or the increase of comorbidities and polypharmacy which could affect adherence to drug-treatment. Trials designed to address this issues are urgently needed, in order to be able to make evidence-guided decisions on lipid management of the elderly.

Older patients are less likely than younger patients to receive anticoagulation and are more likely to be underanticoagulated. Although the use of warfarin in the elderly has been increasing, fewer than half of eligible patients take warfarin. Evidence suggests that stroke recurrence in patients on oral anticoagulation is mainly ischemic, and hemorrhagic complications that derive from oral anticoagulation would be related to overdosing. Several risk factors for developing hemorrhagic complications have been described, and clinical criteria have been designed to help clinicians in decision-making concerning the start of anticoagulation treatment. Finally, given the promising results of recent studies on new anticoagulant drugs, it is possible that vitamin K antagonists will be replaced in the coming years.

Revascularization remains the cornerstone of managing obstructive coronary artery disease. Although percutaneous coronary interventions involving the insertion of metal scaffolds, known as stents, has emerged as the preferred method of restoring vessel patency, as many as 30% of patients will experience a gradual re-narrowing of the lumen caused by neointima (NI) formation, resulting in a condition known as in-stent restenosis (ISR). ISR represents a significant limitation to percutaneous revascularization - however, abrogating NI formation following stent implantation has been hampered by an incomplete understanding of the pathogenesis of in-stent lesions. While numerous mechanisms have been proposed to explain the pathogenesis of ISR, data from human and animal models have yielded conflicting results. Herein, we review key studies of NI development following vascular injury with a focus on the origin of cells participating in NI formation.

Infections of the central nervous system may provoke glial and autoimmune responses but a definitive linkage between these infections and the pathogenesis of chronic neurologic disorders is still elusive. There are controversial reports implicating infectious agents in the pathogenetic mechanisms of chronic or long-term neurologic disorders, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease and autistic spectrum disorders, but the specific role of bacterial or viral infections in the pathogenesis of these medical entities has not been fully elucidated. Up till now, the evidence is distant from definite, but certain cases may be attributed to infections in the millieu of multiple toxic events such as trauma, nutritional deficits, immune dysregulation and excitotoxicity in genetically vulnerable indiniduals. There is an ongoing debate concering the direct involvement of various infectious agents in the neurodegenerative and neurobehavioral diseases pathogenesis and/or their contribution to the deterioration of the disease or co-morbidity in these patients. These patients are exceptionally difficult to be treated by using single therapeutic modalities, because their disese is multifocal and treatment is aimed to control signs and symptoms rather than the true causes of the disease and its progressive course. Furthermore, even if these causative links were indetifiable, our therapeutic interventions would come too late due to the irreversible damages at the time of the initiation of treatment. Our aim is to comprehensively review all available data suggesting that infections could be common antecedent events of progressive neurologic degenerative or behavioural diseases.

Background: Heart Rate Variability (HRV) is a reliable measure of autonomic function. It is positively influenced by treatment with an HMG-CoA reductase inhibitor (statin) with resultant improvement in parasympathetic tone in the general hyperlipidemic population. We tested the hypothesis that autonomic function would improve following 4 weeks of treatment with a statin by conducting a randomized, double-blind, placebo-controlled, cross-over study in 10 subjects. Methods: Stable subjects receiving chronic outpatient hemodialysis were enrolled without regard to lipid status. None of the subjects had received prior statin therapy. They spent the first four weeks of study taking either a placebo or simvastatin (40 mg po qD). They then switched to the other arm for the second four weeks. Measurements of inflammatory mediators and heart rate variability (HRV) were made at baseline and four week intervals. Results: Absolute values of LDL values fell (>25%) with statin treatment. Highly sensitive C-reactive protein (hs-CRP), while demonstrating a trend to improvement, did not change significantly and was associated with a wide standard deviation as well as a baseline elevation well above normal values (baseline = 7.1 ± 6.7 mg/dL, ON statin = 10.8 ± 20.4 mg/dL, OFF statin = 6.9 ± 6.0 mg/dL, p > 0.05 = ns). None of the major time domains of HRV (SDNN, SDANN, RMSSD, or TRIA) responded to statin therapy in a statistically significant manner. Three of four domains did trend upward (indicating an increase in parasympathetic tone) following statin therapy. Conclusions: These data indicate that, unlike the general population, there is no statistically significant impact of statin use on autonomic function in patients on dialysis.