Effect of calendar age on physical performance: A comparison of standard clinical measures with instrumented measures in middle-aged to older adults

BackgroundDecline in physical performance is highly prevalent during aging. Identification of sensitive markers of age-related changes in physical performance is important for early detection, development of therapeutic strategies and insight into underlying mechanisms. We studied the association of calendar age and familial longevity with standard clinical and instrumented measures of physical performance in a cohort of healthy middle-aged to older adults.MethodsCross-sectional analysis within the Leiden Longevity Study consisting of offspring of nonagenarian siblings and their partners (n = 300, mean age (SD) 65.3 (6.7) years). Standard clinical measures were 25-meter walking speed and total duration of the chair stand test (CST). Instrumented measures were determined using a body fixed sensor. Dependence of physical performance on calendar age and familial longevity (offspring versus partner status) was analyzed using linear and logistic regression, respectively, adjusted for gender and height.ResultsHigher calendar age was associated with slower walking speed and longer duration of the CST (standardized β (95% CI) −.024 (−.042; −.006) and .035 (.014;.056), respectively). Instrumented measures showed similar effect sizes with strongest associations for gait stability and symmetry in mediolateral direction and for the extension and flexion phase of sit-to-stand and stand-to-sit transfers, respectively. No differences were observed between offspring of nonagenarian siblings and their partners.ConclusionsStandard clinical and instrumented measures of physical performance are associated with similar effect size to age-related changes in physical performance observable from middle age. The potential added value of instrumented measures for understanding underlying mechanisms requires further attention.     

Primary Aldosteronism: A New Understanding

Primary aldosteronism (PAL) may always have a genetic basis. This leads to either abnormally regulated, increased biosynthesis (Familial Hyperaldosteronism Type I, FHI) or to unrestrained hyperplasia and neoplasia, usually benign. The distinction between diffuse hyperplasia, nodular hyperplasia and adenoma may be relatively unimportant in functional and etiological terms. The genetic basis must be understood before diagnosis of disease (FHI) or of predispostion (all other PAL) can be made at birth and appropriate surveillance commenced. The natural history of PAL other than FHI is for a progressive increase in severity, with both adrenals eventually involved. Long-term follow-up of PAL is therefore mandatory, and postoperative assessment of residual non-suppressible aldosterone production by fludrocortisone suppression testing useful in defining biochemical cure or improvement, and the need for specific medical treatment.     

Centralized Registration,Prophylactic Examination,and Treatment Results in Improved Prognosis in Familial Adenomatous Polyposis: Results from the Danish Polyposis Register

Background: Over the last few decades numerous regional and national registers have been established all over the world with the aim of improving survival in familial adenomatous polyposis (FAP). The Danish Polyposis Register was founded in 1971 and coordinates the screening and subsequent prophylactic colectomy of FAP patients. Methods: The crude cumulative survival in 321 patients (205 probands and 116 call-up cases) with verified FAP was calculated in accordance with the life-table method. Results: At the time of diagnosis of FAP only 2 of 116 (2%) had colorectal cancer versus 142 of 205 probands (69%). The 10-year cumulative survival was 94% (95% confidence limits, 89-99) in call-up cases compared with only 41% (34-49) in probands (p < 0.00001), and survival improved significantly (p < 0.00001) after the establishment of the Danish Polyposis Register. Conclusion: The establishment of a centralized polyposis register has resulted in a substantial improvement of the prognosis in FAP.     

Survival in familial and non-familial breast cancer by age and stage at diagnosis

We aimed to compare the survival in familial and sporadic breast cancer (BC) patients who were diagnosed at an identical age and TNM stage. The Nationwide Swedish Family-Cancer Database including all Swedes born after 1931 and their biological parents, totalling >14.7 million individuals, was used. Hazard ratios (HRs) were calculated for women with BC in a first-degree relative (FDR) versus BC patients without positive family history. There was no difference in survival of familial BC patients who were diagnosed at higher TNM status or older age (>40) compared to sporadic BC cases diagnosed at the same late TNM stage. Young BC patients (age <40) in early stages had the worst survival when their FDR was diagnosed with single (HR: 2.0–3.7) or multiple (HR: 2.4–7.1) BC at any age. We concluded that there is no difference in survival of familial and non-familial BC patients who are diagnosed at higher TNM status or older ages (>40). Young familial BC patients (age <40), diagnosed at early stage, have the poorer survival compared to sporadic cases. Our results urge the need for identifying the underling genetic component for such a difference in survival of familial BC.     

MEFV mutations in familial Mediterranean fever: association of M694V homozygosity with arthritis

Objective Familial Mediterranean fever (FMF) is an autosomal recessive recurrent polyserositis with a higher prevalence in some ethnic groups, including Turks. Mutations in the FMF gene (MEFV) were found associated with FMF. The aim of this study was to analyze MEFV gene mutations in FMF patients to gain insight into the mutation phenotype correlation.Objectives We analyzed the most frequent mutations (M680I, M694V, V726A, and E148Q) in a group of young male Turkish FMF patients using an amplification refractory mutation system and a commercial kit.Results M694V mutation was detected in 80% of the patients. After making a strict diagnostic discrimination between arthralgia and arthritis, arthritis was present in 71% of homozygous and 29.4% of heterozygous patients for M694V mutation. Other mutations were not found to correlate with specific symptoms or findings.Conclusion The homozygosity of M694V mutation in the MEFV gene is associated with arthritis in FMF patients.     

Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction

OBJECTIVES

We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5′-nucleotidase which plays a key role in the IP-induced cardioprotection.

BACKGROUND

The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects.

METHODS

Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5′-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure.

RESULTS

This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5′-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold).

CONCLUSIONS

Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5′-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5′-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.     

Cardiovascular reactivity score for the assessment of dysautonomia in familial Mediterranean fever

Objective The aim of this study was to assess the presence of dysautonomia, as manifested in abnormal cardiovascular reactivity, in patients with familial Mediterranean fever (FMF).Methods Fifty-five consecutive patients with FMF and 23 age- and sex-matched healthy controls were evaluated. Cardiovascular reactivity was studied: (1) using recordings of blood pressure (BP) and heart rate (HR) during 10 min of recumbence and 30 min of head-up tilt test to identify clinical endpoints and (2) during tilt-test, identifying parameters acting as independent predictors of FMF reactivity and enabling computation of a cardiovascular reactivity score (CVRS).Results Clinically, vasovagal reaction, postural tachycardia syndrome, and/or orthostatic hypotension were observed in ten patients (18.1%). Utilizing a derived equation, the group average CVRS in FMF was 5.83±1.78 (healthy group –7.60±5.41) (P=<0.0001). A CVRS of >3.25 was associated with FMF, with 98% sensitivity and 100% specificity.Conclusion A very high percentage of FMF patients exhibit abnormal cardiovascular reactivity which is clinically occult but can be detected on autonomic challenge and application of the CVRS.     

Use of cholesterol-lowering therapy and related beliefs among middle-aged adults after myocardial infarction

OBJECTIVE: To assess use of cholesterol-lowering therapy and related beliefs among middle-aged adults after myocardial infarction. DESIGN: Telephone survey and administrative data. SETTING: National managed-care company. PARTICIPANTS: Six hundred ninety-six adults age 30 to 64 surveyed in 1999, approximately 1 to 2 years after a myocardial infarction. MEASUREMENTS: Use of cholesterol-lowering drugs, beliefs about the importance of lowering cholesterol, and knowledge of personal cholesterol level, adjusting for demographic and clinical factors with logistic regression. MAIN RESULTS: Among respondents, 62.5% reported they were taking a cholesterol-lowering drug. In adjusted analyses, these drugs were used significantly less often by African-American patients and those with congestive heart failure or peripheral vascular disease, and more often by college graduates, patients with hypertension, and those who had seen a cardiologist since their myocardial infarction. Lowering cholesterol was viewed as "very important"; by 87.1% of patients, but significantly less often by smokers and more often by those who had undergone coronary angioplasty or bypass surgery. Only 42.5% of respondents knew their cholesterol level, and this knowledge was significantly less common among less-educated or less-affluent patients, African-American patients, and patients who smoked or had diabetes or peripheral vascular disease. CONCLUSIONS: Although most patients recognized the importance of lowering cholesterol after myocardial infarction, several clinical and demographic subgroups were less likely to receive cholesterol-lowering therapy, and many patients were unaware of their cholesterol level. Health-care providers and managed-care plans can use these findings to promote cholesterol testing and treatment for patients with coronary heart disease who are most likely to benefit from these efforts.     

Soy protein diet significantly improves endothelial function and lipid parameters.

BACKGROUND: Replacement of animal protein with soy protein in the diet is associated with decreased cholesterol levels. However, the effects of soy protein diet on endothelial function are not well known. HYPOTHESIS: The aim of the study was to investigate the effects of soy protein diet on plasma lipids and endothelial function parameters assessed by two different methods. METHODS: Twenty hypercholesterolemic, nonsmoker male patients (age 50.1+/-11.8 years), with a normal body mass index, were included. After calculating their daily requirements, a diet with 25-30% of energy from fats. 10-12% from proteins, and the rest from carbohydrates was instituted. Sixty percent of the animal source proteins of the diet were substituted by soy. The anthropometric measures, lipid parameters, and endothelial functions of the subjects were assessed at baseline and 6 weeks after soy protein diet. Flow-mediated endothelium-dependent dilatation (EDD) and plasma thrombomodulin (TM) levels were evaluated as endothelial function parameters. RESULTS: After diet, plasma total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and triglyceride levels decreased significantly (p <0.001, p < 0.001, p = 0.039, and p = 0.001, respectively). The mean plasma TM levels were also significantly reduced with diet (p = 0.004). Studies of the brachial artery indicated a borderline dilatation in baseline brachial artery diameter (p = 0.05), however the diameter at reactive hyperemia was significantly larger after diet (p<0.001), resulting in a significant improvement of EDD (p = 0.002). CONCLUSION: Soy protein diet significantly improves plasma lipid profile in patients with hypercholesterolemia. Furthermore, the endothelial function, as judged by two different methods (EDD and plasma TM levels), also improves with soy protein diet.