COX-2, NSAIDs, and cardiovascular risk

Clinical studies of selective and nonselective inhibitors of cyclooxygenase-2 (COX-2) provide evidence that inhibition of the enzyme is associated with modestly increased risks of cardiovascular thrombotic events. Investigation of the physiology of COX-2 demonstrates a complex array of interlinked factors affecting its regulation and function. Efficient integration of data from the basic sciences and randomized and observational studies is necessary to fully understand the consequences of COX-2 inhibition and thereby provide guidance for the safe use of COX-2-inhibiting drugs.     

Atherosclerosis and cardiovascular risk factors in the elderly

Atherosclerosis is an age-related process that reflects the interaction between aging and the factors that influence the rate of atherogenesis. The great difficulty in the study of the cardiovascular consequences of aging is due to the fact that it is not easy to distinguish between the effects aging per se (primary aging) and the effects of changes in behaviour and life style that usually accompany old age and may influence the rate of atherogenesis. Most risk factors known to contribute to cardiovascular disease are highly prevalent in the aged and all of them are modifiable. Ideally, preventive measures should be initiated early in the life, when such measures however instituted in the aged, also have beneficial effects. Because incidence rates of atherosclerotic disease are high in the elderly, preventive measures could have a great impact on older persons. Thus interventions aimed to decrease cardiovascular morbidity and mortality will reduce the health costs and improve the quality of the last years of life.     

Blood pressure parameters and cardiovascular risk in the elderly

The treatment decision must take into account the benefit and risks related to the intervention: the benefit demonstrated and quantified in many therapeutic trials in hypertension in the elderly, but also the patient's initial risk. It is now recognized that, in elderly hypertensive patients, systolic blood pressure is a better predictor of morbid and lethal events related to hypertension than diastolic blood pressure. Recent data in the medical literature attribute a predictive role to pulse pressure which is even greater than that of systolic blood pressure. From a pathophysiological point of view, the level of pulse pressure reflects the degree of rigidity of large arterial trunks. The arterial rigidity parameter could integrate the harmful effect of "cardiovascular risk factors" (hypertension, but also atherogenic dyslipidaemia, diabetes, smoking, homocysteine, genetic factors, etc.) on the years or decades of exposure, and pulsed pressure would therefore appear to be a better marker of cardiovascular risk than other blood pressure parameters. Pulse pressure should therefore be integrated into the benefit/risk ratio of antihypertensive treatment in the elderly.     

Statins and C-reactive protein: considering a novel marker of cardiovascular risk

Landmark intervention trials have validated the importance of lipid control in reducing the incidence of coronary ischemic events, over a range of baseline lipid levels. With the release of the third iteration of the National Cholesterol Education Program's Adult Treatment Panel guidelines, there is renewed debate about the appropriate use of pharmacologic therapies in individual patients, especially in primary prevention. Markers of low-grade inflammation may capture the inflammatory aspect of atherosclerosis and may prove to be useful clinical predictors of excess coronary risk. C-reactive protein, an acute-phase reactant protein, appears to be one such promising measurement and may have important implications for the optimal targeting of statin therapy.     

Appropriate drug prescribing in the elderly

PURPOSE: The frequency of chronic illness and the expenditure of medications increase with the older age. If drug-prescribing is very often beneficial for the patients, elderly subjects are particularly exposed to the side-effects of medications, and to their consequences. Although the age in itself do not generally forbid a medication, it can modify some of the objectives and the modality of the treatment. CURRENT KNOWLEDGE AND KEY POINTS: Four main factors explain the growing frequency of the iatrogenic pathology in the old age: polymedication, pharmacological modifications that occur with the ageing process, lack of coordination between different prescribers, and physical and psycho-social deficiencies which are the keys for identifying the "frail elderlies". FUTURE PROSPECTS AND PROJECTS: In regard to the frequent polypathological conditions of the oldest patients, one does not have to consider a sum of sicknesses, but a global situation, and one needs to replace a condition in a general context, and to establish priorities in the goals of the treatment. Appropriate drug-prescribing also needs to take account of the latest medical recommendations concerning numbers of medications, and a more frequent involving of elderly subjects in clinical trials.     

Review on the management of cardiovascular risk factors in the elderly

Cardiovascular risk factors (CVRF) are very prevalent in the elderly population and in addition to predisposing to cardiovascular disease they are related to functional decline, which limits the quality of life in this population. The objective of this work is to offer a review of the current evidence in the management of CVRF in the elderly population. The search strategy was executed in PubMed, Clinicalstrials.org and Embase, to search for clinical trials, observational cohort or cross-sectional studies, reviews, and clinical practice guidelines focused or including elderly population. The results provided were refined after reading the title and abstract, as well as elimination of duplicates, and were finally identified and assessed following the GRADE methodology. A total of 136 studies were obtained for all predefined risk factors, such as sedentary lifestyle, smoking, obesity and metabolic syndrome, hypertension, diabetes mellitus, dyslipidemia and alcohol. We described the results of the studies identified and assessed according to their methodological quality in different recommendation sections: diagnostic and prevention, intervention, or treatment in the elderly population. As the main limitation to the results of this review, there is the lack of quality studies whose target population is elderly patients. This issue limits the recommendations that can be made in this population. Due to this reason, comprehensive geriatric assessment seems the best tool currently available to implement the most appropriate treatment plans based on the baseline situation and comorbidity of each elderly patient.

Cardiovascular risk factors (CVRF) are highly prevalent among older adults, with hypertension being present in around 70%, obesity in 20%−40%, diabetes in 15% and dyslipidaemia in 35%.^[1] Cardiovascular disease (CVD) causes 39% of deaths in octogenarians.^[1] Moreover, its presence in this population is linked to cognitive decline, functional deterioration and dependency, increasing healthcare costs.^[1,2,3]Despite the importance of CVRF, there is still a wide margin for improvement in the management of CVRF in the older population. This is partly because the main risk factor for CVD is age,^[3] which cannot be modified, but also because diagnostic criteria are not adjusted to this age group and their treatment goals do not always include maintaining quality of life and functional status, in addition to survival. There are numerous standards of care and clinical practice guidelines for the management of CVRF aimed at the general population, but recommendations for older adults are scarce and are too general to be easily and safely applied in clinical practice.Moreover, frailty, a particular feature in this age group, is not usually included in guidelines on the management of CVRF and should be included in routine clinical practice since it has a demonstrated relationship with CVD in older adults.^[4] This is particularly important, given the reverse epidemiology of CVRF in older adults, which refers to the loss of predictive power of classical CVRF in persons older than 70 years. Consequently, there is a need to identify other, non-traditional risk factors.The aim of this study was to summarize the current evidence on the management of CVRF in older adults, focusing on the treatment goals specific to this age group, such as functional independence, quality of life, and the management of patients with frailty.     

Fish consumption and stroke risk in elderly individuals: the cardiovascular health study

BACKGROUND: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential. METHODS: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained. RESULTS: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.98) and 30% lower risk with intake of 5 or more times per week (HR, 0.70; 95% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke. CONCLUSIONS: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.     

老年人非甾体抗炎药相关性消化性溃疡病

自1982年澳大利亚学者Warren和Marshall发现胃有幽门螺杆菌(HP)感染后,经多年研究,证实消化性溃疡病(pepticulcerdisease,简称PUD)的发生和复发与HP感染密切相关,称之为HP相关性PUD,将HP根治后,可使PUD治愈,很少复发。近10年来PUD及其引起的并发症与过去相比,确实少多了,归功于根治HP。但由药物引起的PUD相对多了,特别是由非甾体抗炎药(NSAID)所致者更为常见。据观察,长期服用NSAID的病例,大约有10%～15%会发生PUD,其中以胃溃疡多见犤1犦,服NSAID者发生胃溃疡和十二指肠溃疡的危险性比不服此药者分别增大3.2和2.7倍。这种…     

Blood pressure experience and risk of cardiovascular disease in the elderly

For the 1254 persons in the Framingham Heart Study who survived to age 65 without prior cardiovascular disease or prior use of antihypertensive medications, significant univariate correlates of the development of cardiovascular disease after age 65 included (1) the systolic blood pressure at age 65, (2) the average systolic blood pressure before age 65, and (3) the slope of blood pressure change up to age 65. After controlling for the systolic blood pressure at age 65, average pre-age 65 blood pressure remained significant (p less than 0.05) and the slope of the pre-age 65 blood pressure was marginally significant (p = 0.06). Even after controlling for the mean of up to three blood pressure measurements at age 65, an average systolic blood pressure of 160 mm Hg or greater before age 65 was an independently significant predictor of the post-age 65 development of cardiovascular disease (rate ratio = 1.79; 95% confidence interval = 1.04, 3.07). These data suggest that even after performing multiple measurements at a single examination, knowledge of past systolic blood pressure history, especially if it averages 160 mm Hg or greater, adds a small but statistically significant increment in predicting future cardiovascular disease in the elderly.     

Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study

OBJECTIVES: To determine the prognostic role of orthostatic hypotension for cardiovascular disease (CVD) and all‐cause mortality in elderly people. DESIGN: Prospective study. SETTING: Community based. PARTICIPANTS: Five thousand sixty‐four subjects from the Rotterdam study aged 55 and older. MEASUREMENTS: Orthostatic hypotension was measured using a Dinamap automatic blood pressure recorder. Orthostatic hypotension is defined as a decline in systolic blood pressure of 20 mmHg or more or a decline in diastolic blood pressure of 10 mmHg or more from supine to standing position at any of three measurements taken 1, 2, and 3 minutes after standing. RESULTS: At baseline, 901 subjects had orthostatic hypotension. During follow‐up, 668 subjects had coronary heart disease (CHD) (mean follow‐up 6.0 ± 3.5 years), and 1,835 subjects died (mean follow‐up period 7.8 ± 3.8 years). Orthostatic hypotension increased the risk of CHD (hazard ratio (HR)=1.31, 95% confidence interval (CI)=1.08–1.57) and all‐cause mortality (HR=1.22, 95% CI=1.09–1.36), in models adjusted for age and sex. The risk was slightly lower after additional adjustment for cardiovascular risk factors. In analyses stratified for age, the HRs for all‐cause mortality were 1.80 (95% CI 1.25–2.60), 1.13 (0.89–1.42), and 1.27 (95% CI=1.11–1.44), in the first, second, and third tertile of age, respectively. CONCLUSION: Orthostatic hypotension increases the risk of CHD and all‐cause mortality in elderly people. The risk of CVD and mortality is strongest in younger and very old subjects.     

Predicting cardiovascular risk in the elderly in different European countries.

AIMS: The objective of this study was to develop risk functions for coronary heart disease and cardiovascular disease mortality for elderly men in different European countries. METHODS and RESULTS: The FINE Study is a prospective follow-up study of 2170 elderly men aged 65-84 years in Finland, Italy and The Netherlands. During 10 years of follow-up 289 men died from coronary heart disease and 545 men from cardiovascular disease. Risk functions were estimated using logistic regression analysis, in order to take competing causes of death into account. The results of the present study show that total cholesterol and smoking were the most important predictors of coronary heart disease mortality, and HDL cholesterol, systolic blood pressure and smoking of cardiovascular disease mortality. Left ventricular hypertrophy, being subject to coronary heart disease or cardiovascular disease in Finland and The Netherlands and use of antihypertensive medication in Italy, were also important predictors. For estimating the absolute risk of coronary heart disease and cardiovascular disease mortality in the elderly it is necessary to take into account the European country in which they live. CONCLUSION: Total and HDL cholesterol, systolic blood pressure and smoking remain important predictors of coronary heart disease and/or cardiovascular disease mortality in elderly men, but also left ventricular hypertrophy, being subject to coronary heart disease, use of antihypertensive medication and country are predictive of coronary heart disease and cardiovascular disease risk.