Pharmacological treatment of portal hypertension: an evidence-based approach

Continuing advances in the knowledge of the pathophysiology of portal hypertension result in the progressive expansion of the spectrum of drugs with a potential role for clinical practice, with objectives that now tend to include the prevention of the enlargement or even the development of esophageal varices. This systematic review summarizes the evidence of efficacy of drug therapy for portal hypertension and draws recommendations for clinical practice. Although there is not yet enough evidence to support the treatment for the prevention of the development or enlargement of varices, nonselective beta-blockers are the first-choice therapy to prevent the first bleeding in patients with medium or large-sized varices and rebleeding in patients surviving a bleeding episode. The clinical role of isosorbide-5-mononitrate either alone or in association with beta-blockers still remains unsettled. Vasoactive drugs are generally effective and safe in controlling acute variceal bleeding, although the evidence is not equivalent for each of them.     

Therapeutic and physical fitness exercise prescription for older adults with joint disease: an evidence-based approach

Aging with joint disease does necessarily result in chronic pain, adoption of a sedentary lifestyle, and functional dependency. Several randomized controlled trials clearly show that regular exercise does not exacerbate pain or accelerate disease progression. On the contrary, these studies suggest that exercise training may increase the physiologic reserve and reduce the risk for functional dependency in older adults with joint disease. The goals for an exercise program should be directed toward increasing flexibility, muscle strength, endurance, and cardiovascular fitness. An exercise training program that is tailored specifically to an older adult's physical limitations may achieve these goals, and by optimizing patient safety lead to improve long-term exercise compliance.     

Blood pressure components and cardiovascular events in older adults: the Rotterdam study

OBJECTIVES: To compare the strength of the relative risks of systolic (SBP) diastolic blood pressure (DBP) and pulse pressure (PP) as predictors of myocardial infarction and stroke in older adults. DESIGN: Prospective cohort study. SETTING: The Rotterdam Study, a Dutch population-based study. PARTICIPANTS: A total of 4,234 subjects aged 55 and older with no previous myocardial infarction (MI) or stroke at baseline. MEASUREMENTS: Blood pressure levels at baseline, first MI and stroke, all-cause mortality during follow-up. RESULTS: During follow-up, 205 subjects had an MI (average follow-up period 7 years), 137 subjects had a stroke (average follow-up period 6.1 years), and 748 subjects died. A 1-standard deviation difference in SBP, DBP, and PP was associated with relative risks of MI of 1.24 (95% confidence interval (CI)=1.06-1.46), 1.07 (0.92-1.25), and 1.25 (1.07-1.48), respectively. Corresponding relative risks for stroke were 1.59 (1.37-1.86), 1.27 (1.10-1.48), and 1.48 (1.27-1.72). For all-cause mortality the corresponding relative risks and 95% CI were 1.21 (1.11-1.31), 1.06 (0.99-1.14), and 1.20 (1.10-1.31). CONCLUSION: The results of this study suggest that, in a population of apparently healthy older adults, PP is not a better predictor of cardiovascular events and all-cause mortality than SBP.     

Prevention of heart failure in older adults may require higher levels of physical activity than needed for other cardiovascular events

Background

Little is known if the levels of physical activity required for the prevention of incident heart failure (HF) and other cardiovascular events vary in community-dwelling older adults.

Methods

We studied 5503 Cardiovascular Health Study (CHS) participants, age ≥ 65 years, free of baseline HF. Weekly metabolic equivalent task-minutes (MET-minutes), estimated using baseline total leisure-time energy expenditure, were used to categorize participants into four physical activity groups: inactive (0 MET-minutes; n = 489; reference), low (1–499; n = 1458), medium (500–999; n = 1086) and high (≥ 1000; n = 2470).

Results

Participants had a mean (± SD) age of 73 (± 6) years, 58% were women, and 15% African American. During 13 years of follow-up, centrally-adjudicated incident HF occurred in 26%, 23%, 20%, and 19% of participants with no, low, medium and high physical activity, respectively (trend p < 0.001). Compared with inactive older adults, age–sex–race-adjusted hazard ratios (95% confidence intervals) for incident HF associated with low, medium and high physical activity were 0.87 (0.71–1.06; p = 0.170), 0.68 (0.54–0.85; p = 0.001) and 0.60 (0.49–0.74; p < 0.001), respectively (trend p < 0.001). Only high physical activity had significant independent association with lower risk of incident HF (HR, 0.79; 95% CI, 0.64–0.97; p = 0.026). All levels of physical activity had significant independent association with lower risk of incident acute myocardial infarction (AMI), stroke and cardiovascular mortality.

Conclusion

In community-dwelling older adults, high level of physical activity was associated with lower risk of incident HF, but all levels of physical activity were associated with lower risk of incident AMI, stroke, and cardiovascular mortality.     

Novel approach to examining first cardiovascular events after hypertension onset

Hypertension confers risk for multiple types of cardiovascular events, but competing risks for these outcomes are unknown. We estimated the competing risks over 12 years after hypertension onset among cases and age-, sex-, and examination-matched controls using competing Cox cumulative incidence and proportional hazards models. We included all Framingham Heart Study subjects examined after 1977 with new-onset hypertension who were free of cardiovascular disease. There were 645 men and 702 women with new-onset hypertension (mean age: men, 55+/-12 years; women, 59+/-12 years). Compared with matched nonhypertensive controls, subjects with new-onset hypertension were more likely to experience a cardiovascular event first rather than noncardiovascular death. Among new-onset hypertensives, the 12-year competing cumulative incidence of any cardiovascular end point as a first event in men was 24.7%, compared with 9.8% for noncardiovascular death (hazards ratio [HR], 2.53; 95% confidence interval [CI], 1.83 to 3.50); in women, the competing incidences were 16.0% versus 10.1%, respectively (HR, 1.58; 95% CI, 1.13 to 2.20). The most common first major cardiovascular events were hard coronary disease (8.2%) in men and stroke (5.2%) in women. Type and incidence of first cardiovascular events varied by age and severity of hypertension at onset, with stroke predominating among older subjects with new-onset hypertension. After hypertension onset, cardiovascular events are more likely to occur first as opposed to noncardiovascular death. Types of initial events differ by gender, age, and severity of hypertension at onset. These results represent a novel approach to understanding the complications of hypertension and may help target therapies for patients with new-onset hypertension to optimize prevention strategies.     

Pulmonary hypertension in older adults

Pulmonary hypertension is a frequently encountered problem in older patients. True idiopathic pulmonary arterial hypertension can also be seen and requires careful exclusion in older patients. Institution of therapies must be tempered with an appreciation of individual comorbidities and functional limitations that may affect patients' ability to comply and benefit from the complex treatments available for pulmonary arterial hypertension. This article reviews the existing data on the various forms of pulmonary hypertension presenting in older patients and on appropriate therapy in this challenging population.     

Treatment of knee pain in older adults in primary care: development of an evidence-based model of care

OBJECTIVE: To develop a stepped model of care for the treatment of knee pain in older adults in primary care based on recommended interventions. METHODS: A systematic search was undertaken to identify interventions recommended for knee osteoarthritis or knee pain in clinical guidelines and systematic reviews. Following this, a nominal group consensus exercise was conducted with members of the Primary Care Rheumatology Society to allocate the interventions to a stepped model of care. RESULTS: Twenty-seven recommended interventions were identified from 77 publications following the systematic search. A four-step model of care incorporating these interventions was developed through the consensus exercise. Step 1 comprised ten interventions that should be offered to all older adults with knee pain, but could also be provided through self-care. These included exercise, weight loss, paracetamol and written information. Steps 2 and 3 comprised 10 and 6 interventions, respectively, to be considered for people with persisting pain and disability. These included pharmacological interventions such as non-steroidal anti-inflammatory drugs in step 2 and intra-articular corticosteroids in step 3, and non-pharmacological interventions such as physiotherapy in step 2 and occupational therapy in step 3. Step 4 was referral for surgery. CONCLUSIONS: Previous evidence-based guidelines for the treatment of knee problems have been developed in secondary care. A systematic search for recommended interventions, and a consensus exercise, has now enabled an evidence-based and practical model of care for knee pain in older adults to be developed for use in primary care.     

Prevention of cardiovascular events in elderly hypercholesterolemic patients

The management of hyperlipidemia in the elderly patient is a major problem, given the frequency of dyslipidemias and cardiovascular disorders in this age group. Therapy must take current uncertainties into account and, in the absence of therapeutic studies carried out in the elderly, is typically based upon a case-by-case approach. Raised cholesterol levels remain a significant risk factor for coronary heart disease (CHD) in the elderly. Although the relative risk of CHD tends to diminish with increasing age, this reduction is accompanied by an increase in absolute risk (ie, the number of events) as the frequency of the illness increases markedly with age. The results of major outcome studies with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), when analyzed according to patient age, indicate that the benefits of these agents are not merely confined to younger individuals. However, the elderly form a unique patient population—the proportion of women is greater and the profile of cardiovascular illnesses is characterized, among others, by a greater incidence of cerebrovascular accidents. Problems relating to poor tolerability and comorbidity (which may give rise to drug-drug interactions) also occur more frequently in this age group. Moreover, the potential widespread treatment of hyperlipidemia in the elderly has profound economic implications. Under these circumstances, the clinical practice recommendations depend upon a reasonable extrapolation of epidemiologic and therapeutic data obtained from middle-aged men. At present, treatment is therefore aimed at patients with the most severe forms of hyperlipidemia, generally in the secondary prevention setting, taking into account the patient’s life expectancy. The results of ongoing studies will determine the benefits of lipid-lowering therapy for primary prevention of CHD in the elderly.     

Diets and cardiovascular disease: an evidence-based assessment

With rising obesity, despite low-fat diet recommendations, there is an increased interest in weight loss and alternative dietary approaches for cardiovascular health. Physicians must have an understanding of the literature to better counsel their patients about diets and cardiovascular disease. This review examines several dietary approaches to cardiovascular health and evaluates the available scientific evidence regarding these diets.     

Small artery structure is an independent predictor of cardiovascular events in essential hypertension

OBJECTIVE: Structural abnormality of resistance arteries is a characteristic pathophysiological phenomenon in essential hypertension and can be assessed in vitro as an increase in the media: lumen ratio (M: L) of isolated small arteries. We have investigated whether M: L is a risk predictor in uncomplicated essential hypertensive patients. Recently, high M: L was demonstrated as a prognostic marker in patients at high cardiovascular risk, including normotensive type 2 diabetic patients. Since diabetes is associated with pressure-independent changes in M: L, the relevance of this finding to essential hypertension has been uncertain. METHODS: We conducted a follow-up survey of 159 essential hypertensive patients, who had previously been submitted to a M: L evaluation while participating in a clinical trial. They composed a homogeneous moderate-risk group, with no concomitant diseases, and represented 1661 years of follow-up. RESULTS: Thirty patients suffered a documented predefined cardiovascular event during follow-up. Increased relative risk (RR) was associated with M: L >or= 0.083 (mean level of the hypertensive cohort), RR = 2.34 [95% confidence interval (CI) 1.11-4.95], and with M: L >or= 0.098 (mean level of a normotensive control group + 2SD), RR = 2.49 (95% CI 1.21-5.11). Both results remained significant (RR = 2.19, 95% CI 1.04-4.64, and RR = 2.20, 95% CI 1.06-4.56, respectively) when adjusted for Heart Score level (10-year mortality risk-estimate, integrating age, gender, systolic blood pressure, cholesterol and smoking). CONCLUSION: Abnormal resistance artery structure independently predicts cardiovascular events in essential hypertensive patients at moderate risk.