Real-world effectiveness of pneumococcal vaccination in older adults: Cohort study using the UK Clinical Practice Research Datalink.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for UK older adults, but how age moderates effectiveness is unclear. METHODS: Three annual cohorts of primary-care patients aged≥65y from the Clinical Practice Research Datalink selected from 2003-5 created a natural experiment (n = 324,804), reflecting the staged introduction of the vaccine. The outcome was symptoms consistent with community-acquired pneumococcal pneumonia (CAP) requiring antibiotics or hospitalisation. We used the prior event rate ratio (PERR) approach to address bias from unmeasured confounders. RESULTS: Vaccinated patients had higher rates of CAP in the year before vaccination than their controls, indicating the potential for confounding bias. After adjustment for confounding using the prior event rate ratio (PERR) method, PPV23 was estimated to be effective against CAP for two years after vaccination in all age sub-groups with hazard ratios (95% confidence intervals) of 0.86 (0.80 to 0.93), 0.74 (0.65 to 0.85) and 0.65 (0.57 to 0.74) in patients aged 65-74, 75-79 and 80+ respectively in the 2005 cohort. Age moderated the effect of vaccination with predicted risk reductions of 8% at 65y and 29% at 80y. CONCLUSIONS: PPV23 is moderately effective at reducing CAP among UK patients aged≥65y, in the two years after vaccination. Vaccine effectiveness is maintained, and may increase, in the oldest age groups in step with increasing susceptibility to CAP.

Influenza vaccination reduced myocardial infarctions in United Kingdom older adults: a prior event rate ratio study.

OBJECTIVES: We aimed to estimate the real-world effectiveness of the influenza vaccine against myocardial infarction (MI) and influenza in the decade since adults aged ≥ 65 years were first recommended the vaccine. STUDY DESIGN AND SETTING: We identified annual cohorts, 1997 to 2011, of adults aged ≥ 65 years, without previous influenza vaccination, from UK general practices, registered with the Clinical Practice Research Datalink. Using a quasi-experimental study design to control for confounding bias, we estimated influenza vaccine effectiveness on hospitalization for MI, influenza, and antibiotic prescriptions for lower respiratory tract infections. RESULTS: Vaccination was moderately effective against influenza, the prior event rate ratio-adjusted hazard ratios ranging from 0.70 in 1999 to 0.99 in 2001. Prior event rate ratio-adjusted hazard ratios demonstrated a protective effect against MIs, varying between 0.40 in 2010 and 0.89 in 2001. Aggregated across the cohorts, influenza vaccination reduced the risk of MIs by 39% (95% confidence interval: 34%, 44%). CONCLUSION: Effectiveness of the flu vaccine in preventing MIs in older UK adults is consistent with the limited evidence from clinical trials. Similar trends in effectiveness against influenza and against MIs suggest the risk of influenza mediates the effectiveness against MIs, although divergence in some years implies the mechanism may be complex.

The Relationship Between Endoscopic and Clinical Recurrence in Postoperative Crohn's Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: We aimed to quantify the magnitude of the association between endoscopic recurrence and clinical recurrence [symptom relapse] in patients with postoperative Crohn's disease. METHODS: Databases were searched to October 2, 2020, for randomised controlled trials [RCTs] and cohort studies of adult patients with Crohn's disease with ileocolonic resection and anastomosis. Summary effect estimates for the association between clinical recurrence and endoscopic recurrence were quantified by risk ratios [RR] and 95% confidence intervals [95% CI]. Mixed-effects meta-regression evaluated the role of confounders. Spearman correlation coefficients were calculated to assess the relationship between these outcomes as endpoints in RCTs. An exploratory mixed-effects meta-regression model with the logit of the rate of clinical recurrence as the outcome and the rate of endoscopic recurrence as a predictor was also evaluated. RESULTS: In all, 37 studies [N = 4053] were included. For eight RCTs with available data, the RR for clinical recurrence for patients who experienced endoscopic recurrence was 10.77 [95% CI 4.08 to 28.40; GRADE moderate certainty evidence]; the corresponding estimate from 11 cohort studies was 21.33 [95% CI 9.55 to 47.66; GRADE low certainty evidence]. A single cohort study showed a linear relationship between Rutgeerts score and clinical recurrence risk. There was a strong correlation between endoscopic recurrence and clinical recurrence treatment effect estimates as trial outcomes [weighted Spearman correlation coefficient 0.51]. CONCLUSIONS: The associations between endoscopic recurrence and subsequent clinical recurrence lend support to the choice of endoscopic recurrence to monitor postoperative disease activity and as a primary endpoint in clinical trials of postoperative Crohn's disease.

Proton-Pump Inhibitors and Long-Term Risk of Community-Acquired Pneumonia in Older Adults.

OBJECTIVES: To estimate associations between long-term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care. DESIGN: Longitudinal analyses of electronic medical records. SETTING: England PARTICIPANTS: Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age- and sex-matched controls (N=75,050). MEASUREMENTS: Net hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures. RESULTS: During the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR-adjusted hazard ratio=1.82, 95% confidence interval=1.27-2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score- and inverse probability-weighted models. CONCLUSION: In a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short-term harms of PPIs should not divert attention from potential long-term effects of PPI prescriptions on older adults.

Blood Pressure Trajectories in the 20 Years Before Death.

Importance: There is mixed evidence that blood pressure (BP) stabilizes or decreases in later life. It is also unclear whether BP trajectories reflect advancing age, proximity to end of life, or selective survival of persons free from hypertension. Objective: To estimate individual patient BP for each of the 20 years before death and identify potential mechanisms that may explain trajectories. Design, Study, and Participants: We analyzed population-based Clinical Practice Research Datalink primary care and linked hospitalization electronic medical records from the United Kingdom, using retrospective cohort approaches with generalized linear mixed-effects modeling. Participants were all available individuals with BP measures over 20 years, yielding 46 634 participants dying aged at least 60 years, from 2010 to 2014. We also compared BP slopes from 10 to 3 years before death for 20 207 participants who died, plus 20 207 birth-year and sex-matched participants surviving longer than 9 years. Main Outcomes and Measures: Clinically recorded individual patient repeated systolic BP (SBP) and diastolic BP (DBP). Results: In 46 634 participants (51.7% female; mean [SD] age at death, 82.4 [9.0] years), SBPs and DBPs peaked 18 to 14 years before death and then decreased progressively. Mean changes in SBP from peak values ranged from -8.5 mm Hg (95% CI, -9.4 to -7.7) for those dying aged 60 to 69 years to -22.0 mm Hg (95% CI, -22.6 to -21.4) for those dying at 90 years or older; overall, 64.0% of individuals had SBP changes of greater than -10 mm Hg. Decreases in BP appeared linear from 10 to 3 years before death, with steeper decreases in the last 2 years of life. Decreases in SBP from 10 to 3 years before death were present in individuals not treated with antihypertensive medications, but mean yearly changes were steepest in patients with hypertension (-1.58; 95% CI, -1.56 to -1.60 mm Hg vs -0.70; 95% CI, -0.65 to -0.76 mm Hg), dementia (-1.81; 95% CI, -1.77 to -1.87 mm Hg vs -1.41; 95% CI, -1.38 to -1.43 mm Hg), heart failure (-1.66; 95% CI, -1.62 to -1.69 mm Hg vs -1.37; 95% CI, -1.34 to -1.39 mm Hg), and late-life weight loss. Conclusions and Relevance: Mean SBP and DBP decreased for more than a decade before death in patients dying at 60 years and older. These BP decreases are not simply attributable to age, treatment of hypertension, or better survival without hypertension. Late-life BP decreases may have implications for risk estimation, treatment monitoring, and trial design.

Central adiposity and the overweight risk paradox in aging: follow-up of 130,473 UK Biobank participants.

Background: For older groups, being overweight [body mass index (BMI; in kg/m2): 25 to <30] is reportedly associated with a lower or similar risk of mortality than being normal weight (BMI: 18.5 to <25). However, this "risk paradox" is partly explained by smoking and disease-associated weight loss. This paradox may also arise from BMI failing to measure fat redistribution to a centralized position in later life.Objective: This study aimed to estimate associations between combined measurements of BMI and waist-to-hip ratio (WHR) with mortality and incident coronary artery disease (CAD).Design: This study followed 130,473 UK Biobank participants aged 60-69 y (baseline 2006-2010) for ≤8.3 y (n = 2974 deaths). Current smokers and individuals with recent or disease-associated (e.g., from dementia, heart failure, or cancer) weight loss were excluded, yielding a "healthier agers" group. Survival models were adjusted for age, sex, alcohol intake, smoking history, and educational attainment. Population and sex-specific lower and higher WHR tertiles were <0.91 and ≥0.96 for men and <0.79 and ≥0.85 for women, respectively.Results: Ignoring WHR, the risk of mortality for overweight subjects was similar to that for normal-weight subjects (HR: 1.09; 95% CI: 0.99, 1.19; P = 0.066). However, among normal-weight subjects, mortality increased for those with a higher WHR (HR: 1.33; 95% CI: 1.08, 1.65) compared with a lower WHR. Being overweight with a higher WHR was associated with substantial excess mortality (HR: 1.41; 95% CI: 1.25, 1.61) and greatly increased CAD incidence (sub-HR: 1.64; 95% CI: 1.39, 1.93) compared with being normal weight with a lower WHR. There was no interaction between physical activity and BMI plus WHR groups with respect to mortality.Conclusions: For healthier agers (i.e., nonsmokers without disease-associated weight loss), having central adiposity and a BMI corresponding to normal weight or overweight is associated with substantial excess mortality. The claimed BMI-defined overweight risk paradox may result in part from failing to account for central adiposity, rather than reflecting a protective physiologic effect of higher body-fat content in later life.

Relationship Between Urinary Nitrate Excretion and Blood Pressure in the InChianti Cohort.

BACKGROUND: Inorganic nitrate from the oxidation of endogenously synthesized nitric oxide (NO) or consumed in the diet can be reduced to NO via a complex enterosalivary circulation pathway. The relationship between total nitrate exposure by measured urinary nitrate excretion and blood pressure in a large population sample has not been assessed previously. METHODS: For this cross-sectional study, 24-hour urinary nitrate excretion was measured by spectrophotometry in the 919 participants from the InChianti cohort at baseline and blood pressure measured with a mercury sphygmomanometer. RESULTS: After adjusting for age and sex only, diastolic blood pressure was 1.9 mm Hg lower in subjects with ≥2 mmol urinary nitrate excretion compared with those excreting <1 mmol nitrate in 24 hours: systolic blood pressure was 3.4 mm Hg (95% confidence interval (CI): -3.5 to -0.4) lower in subjects for the same comparison. Effect sizes in fully adjusted models (for age, sex, potassium intake, use of antihypertensive medications, diabetes, HS-CRP, or current smoking status) were marginally larger: systolic blood pressure in the ≥2 mmol urinary nitrate excretion group was 3.9 (CI: -7.1 to -0.7) mm Hg lower than in the comparison <1 mmol excretion group. CONCLUSIONS: Modest differences in total nitrate exposure are associated with lower blood pressure. These differences are at least equivalent to those seen from substantial (100 mmol) reductions in sodium intake.

Outcomes of Treated Hypertension at Age 80 and Older: Cohort Analysis of 79,376 Individuals.

OBJECTIVES: To estimate outcomes according to attained blood pressure (BP) in the oldest adults treated for hypertension in routine family practice. DESIGN: Cohort analysis of primary care inpatient and death certificate data for individuals with hypertension. SETTING: Primary care practices in England (Clinical Practice Research Datalink). PARTICIPANTS: Individuals aged 80 and older taking antihypertensive medication and free of dementia, cancer, coronary heart disease, stroke, heart failure, and end-stage renal failure at baseline. MEASUREMENTS: Outcomes were mortality, cardiovascular events, and fragility fractures. Systolic BP (SBP) was grouped in 10-mmHg increments from less than 125 to 185 mmHg or more (reference 145-154 mmHg). RESULTS: Myocardial infarction hazards increased linearly with increasing SBP, and stroke hazards increased for SBP of 145 mmHg or greater, although lowest mortality was in individuals with SBP of 135 to 154 mmHg. Mortality of the 13.1% of patients with SBP less than 135 mmHg was higher than that of the reference group (Cox hazard ratio=1.25, 95% confidence interval=1.19-1.31; equating to one extra death per 12.6 participants). This difference in mortality was consistent over short- and long-term follow-up; adjusting for diastolic BP did not change the risk. Incident heart failure rates were higher in those with SBP less than 125 mmHg than in the reference group. CONCLUSION: In routine primary care, SBP less than 135 mmHg was associated with greater mortality in the oldest adults with hypertension and free of selected potentially confounding comorbidities. Although important confounders were accounted for, observational studies cannot exclude residual confounding. More work is needed to establish whether unplanned SBPs less than 135 mmHg in older adults with hypertension may be a useful clinical sign of poor prognosis, perhaps requiring clinical review of overall care.

Safety and Effectiveness of Statins for Prevention of Recurrent Myocardial Infarction in 12 156 Typical Older Patients: A Quasi-Experimental Study.

BACKGROUND: There is limited evidence on statin risk and effectiveness for patients aged 80+. We estimated risk of recurrent myocardial infarction, muscle-related and other adverse events, and statin-related incremental costs in "real-world" older patients treated with statins versus no statins. METHODS: We used primary care electronic medical records from the UK Clinical Practice Research Datalink. Subhazard ratios (competing risk of death) for myocardial infarction recurrence (primary end point), falls, fractures, ischemic stroke, and dementia, and hazard ratios (Cox) for all-cause mortality were used to compare older (60+) statin users and 1:1 propensity-score-matched controls (n = 12,156). Participants were followed-up for 10 years. RESULTS: Mean age was 76.5±9.2 years; 45.5% were women. Statins were associated with near significant reduction in myocardial infarction recurrence (subhazard ratio = 0.84, 0.69-1.02, p = .073), with protective effect in the 60-79 age group (0.73, 0.57-0.94) but a nonsignificant result in the 80+ group (1.06, 0.78-1.44; age interaction p = .094). No significant associations were found for stroke or dementia. Data suggest an increased risk of falls (1.36, 1.17-1.60) and fractures (1.33, 1.04-1.69) in the first 2 years of treatment, particularly in the 80+ group. Treatment was associated with lower all-cause mortality. Statin use was associated with health care cost savings in the 60-79 group but higher costs in the 80+ group. CONCLUSIONS: Estimates of statin effectiveness for the prevention of recurrent myocardial infarction in patients aged 60-79 years were similar to trial results, but more evidence is needed in the older group. There may be an excess of falls and fractures in very old patients, which deserves further investigation.

Obesity in Older People With and Without Conditions Associated With Weight Loss: Follow-up of 955,000 Primary Care Patients.

BACKGROUND: Moderate obesity in later life may improve survival, prompting calls to revise obesity control policies. However, this obesity paradox may be due to confounding from smoking, diseases causing weight-loss, plus varying follow-up periods. We aimed to estimate body mass index (BMI) associations with mortality, incident type 2 diabetes, and coronary heart disease in older people with and without the above confounders. METHODS: Cohort analysis in Clinical Practice Research Datalink primary care, hospital and death certificate electronic medical records in England for ages 60 to more than 85 years. Models were adjusted for age, gender, alcohol use, smoking, calendar year, and socioeconomic status. RESULTS: Overall, BMI 30-34.9 (obesity class 1) was associated with lower overall death rates in all age groups. However, after excluding the specific confounders and follow-up less than 4 years, BMI mortality risk curves at age 65-69 were U-shaped, with raised risks at lower BMIs, a nadir between 23 and 26.9 and steeply rising risks above. In older age groups, mortality nadirs were at modestly higher BMIs (all <30) and risk slopes at higher BMIs were less marked, becoming nonsignificant at age 85 and older. Incidence of diabetes was raised for obesity-1 at all ages and for coronary heart disease to age 84. CONCLUSIONS: Obesity is associated with shorter survival plus higher incidence of coronary heart disease and type 2 diabetes in older populations after accounting for the studied confounders, at least to age 84. These results cast doubt on calls to revise obesity control policies based on the claimed risk paradox at older ages.

Any versus long-term prescribing of high risk medications in older people using 2012 Beers Criteria: results from three cross-sectional samples of primary care records for 2003/4, 2007/8 and 2011/12.

BACKGROUND: High risk medications are commonly prescribed to older US patients. Currently, less is known about high risk medication prescribing in other Western Countries, including the UK. We measured trends and correlates of high risk medication prescribing in a subset of the older UK population (community/institutionalized) to inform harm minimization efforts. METHODS: Three cross-sectional samples from primary care electronic clinical records (UK Clinical Practice Research Datalink, CPRD) in fiscal years 2003/04, 2007/08 and 2011/12 were taken. This yielded a sample of 13,900 people aged 65 years or over from 504 UK general practices. High risk medications were defined by 2012 Beers Criteria adapted for the UK. Using descriptive statistical methods and regression modelling, prevalence of 'any' (drugs prescribed at least once per year) and 'long-term' (drugs prescribed all quarters of year) high risk medication prescribing and correlates were determined. RESULTS: While polypharmacy rates have risen sharply, high risk medication prevalence has remained stable across a decade. A third of older (65+) people are exposed to high risk medications, but only half of the total prevalence was long-term (any = 38.4 % [95 % CI: 36.3, 40.5]; long-term = 17.4 % [15.9, 19.9] in 2011/12). Long-term but not any high risk medication exposure was associated with older ages (85 years or over). Women and people with higher polypharmacy burden were at greater risk of exposure; lower socio-economic status was not associated. Ten drugs/drug classes accounted for most of high risk medication prescribing in 2011/12. CONCLUSIONS: High risk medication prescribing has not increased over time against a background of increasing polypharmacy in the UK. Half of patients receiving high risk medications do so for less than a year. Reducing or optimising the use of a limited number of drugs could dramatically reduce high risk medications in older people. Further research is needed to investigate why the oldest old and women are at greater risk. Interventions to reduce high risk medications may need to target shorter and long-term use separately.

Much more medicine for the oldest old: trends in UK electronic clinical records.

BACKGROUND: the oldest old (85+) pose complex medical challenges. Both underdiagnosis and overdiagnosis are claimed in this group. OBJECTIVE: to estimate diagnosis, prescribing and hospital admission prevalence from 2003/4 to 2011/12, to monitor trends in medicalisation. DESIGN AND SETTING: observational study of Clinical Practice Research Datalink (CPRD) electronic medical records from general practice populations (eligible; n = 27,109) with oversampling of the oldest old. METHODS: we identified 18 common diseases and five geriatric syndromes (dizziness, incontinence, skin ulcers, falls and fractures) from Read codes. We counted medications prescribed ≥1 time in all quarters of studied years. RESULTS: there were major increases in recorded prevalence of most conditions in the 85+ group, especially chronic kidney disease (stages 3-5: prevalence <1% rising to 36.4%). The proportions of the 85+ group with ≥3 conditions rose from 32.2 to 55.1% (27.1 to 35.1% in the 65-84 year group). Geriatric syndrome trends were less marked. In the 85+ age group the proportion receiving no chronically prescribed medications fell from 29.6 to 13.6%, while the proportion on ≥3 rose from 44.6 to 66.2%. The proportion of 85+ year olds with ≥1 hospital admissions per year rose from 27.6 to 35.4%. CONCLUSIONS: there has been a dramatic increase in the medicalisation of the oldest old, evident in increased diagnosis (likely partly due to better record keeping) but also increased prescribing and hospitalisation. Diagnostic trends especially for chronic kidney disease may raise concerns about overdiagnosis. These findings provide new urgency to questions about the appropriateness of multiple diagnostic labelling.

The Relationship between Heart Rate Variability and Adiposity Differs for Central and Overall Adiposity.

While frank obesity is associated with reduced HRV, indicative of poorer autonomic nervous system (ANS) function, the association between body mass index (BMI) and HRV is less clear. We hypothesized that effects of adiposity on ANS are mostly mediated by visceral fat and less by subcutaneous fat; therefore, centrally distributed adipose tissue, that is, waist circumference (WC), should be more strongly associated with HRV than overall adiposity (BMI). To examine this hypothesis, we used data collected in a subset of the Baltimore Longitudinal Study of Aging to compare strength of association between HRV and WC to that of HRV and BMI. Time domain HRV variables SDNN (standard deviation of successive differences in normal-to-normal (N-N) intervals) and RMSSD (root mean square of successive differences in N-N intervals) were calculated from 24-hour Holter recordings in 159 participants (29-96 years). Increasing WC was associated with decreasing SDNN and RMSSD in younger but not older participants (P value for WC-by-age interaction = 0.003). BMI was not associated with either SDNN or RMSSD at any age. In conclusion, central adiposity may contribute to sympathetic and parasympathetic ANS declines early in life.

Antiproteinuric effect of chemokine C-C motif ligand 2 inhibition in subjects with acute proliferative lupus nephritis.

BACKGROUND/AIMS: To test the role of chemokine C-C motif ligand 2 (CCL2) in the pathogenesis of lupus nephritis (LN), we evaluated the effects of CCL2 inhibition by bindarit therapy in patients with systemic lupus and active renal disease. METHODS: In this proof-of-concept, prospective, randomized, double-blind clinical study, 22 subjects with acute LN were assigned on a 1:1 ratio to 24-week treatment with bindarit (1,200 mg/day) or matching placebo. All subjects were on the same standardized steroid background therapy. Urinary CCL2, urinary albumin excretion (UAE), estimated glomerular filtration rate, time to remission and time to relapse of LN were compared between groups. RESULTS: Urinary CCL2 significantly decreased during bindarit therapy (p = 0.008 vs. baseline) with a reduction that approximated 50% at study end. CCL2 reduction was paralleled by a persistent reduction in UAE that averaged 80% vs. baseline and approximated 90% at study end. Renal function recovery was similar and no difference was found in terms of time to remission and time to relapse of LN between treatment arms. Treatment was safe and well tolerated in all patients. CONCLUSION: In lupus subjects with active nephritis, bindarit significantly reduced albuminuria and urinary CCL2 levels. This study provides the background for longer trials to test renoprotective effect of CCL2 inhibition in LN.

Elevated C-reactive protein levels and metabolic syndrome in the elderly: The role of central obesity data from the InChianti study.

Metabolic syndrome (MS) and "low grade" systemic inflammation (LGSI) are very common findings in the older population. Although MS and LGSI have been associated in adults, it is not known what is the real contribution of MS, and its single components, to LGSI in older persons, due to the potential confounding effect of comorbidity and aging. We investigated the relationship between increased C-reactive protein (CRP) plasma levels, a marker of LGSI, and MS in 1044 older (> or =65 years) community dwelling Italian individuals enrolled the InChianti study. Metabolic syndrome was defined by the NCEP-ATP III-AHA/NHLBI criteria. High sensitivity CRP (hs.CRP) levels were measured by enzyme-linked immunosorbent assay, and defined as high when >3mg/L. The overall prevalence of MS was 31%. The prevalence of high hs.CRP was 54.5% in subjects with, and 41.3% in those without MS (p<0.001). MS was associated with high hs.CRP levels after adjustment for age, gender, and comorbidity (OR: 1.93, 95% CI: 1.46-2.55). Compared to subjects with MS and no LGSI, individuals with MS and LGSI were characterized by higher waist circumference, BMI, and HOMA score. Multivariate logistic regression analysis confirmed the association between waist circumference and high hs.CRP levels in subjects with MS (waist circumference III vs. I tertile OR: 2.60, 95% CI: 1.79-3.77) independent of age, gender, and important confounding variables including comorbidity. Additional analyses, conducted with and without dichotomization of hs.CRP levels, confirmed the central role of waist circumference in the LGSI phenomenon, independent of gender and diagnosis of MS. We conclude that in older individuals, MS is associated with LGSI, but the association is mainly supported by a strong independent correlation between waist circumference and high hs.CRP levels. In the absence of this specific MS component, it seems that the contribution of MS to LGSI would be modest at best.

High basal metabolic rate is a risk factor for mortality: the Baltimore Longitudinal Study of Aging.

BACKGROUND: Despite longstanding controversies from animal studies on the relationship between basal metabolic rate (BMR) and longevity, whether BMR is a risk factor for mortality has never been tested in humans. We evaluate the longitudinal changes in BMR and the relationship between BMR and mortality in the Baltimore Longitudinal Study of Aging (BLSA) participants. METHODS: BMR and medical information were collected at the study entry and approximately every 2 years in 1227 participants (972 men) over a 40-year follow-up. BMR, expressed as kcal/m(2)/h, was estimated from the basal O(2) consumption and CO(2) production measured by open-circuit method. Data on all-cause and specific-cause mortality were also obtained. RESULT: BMR declined with age at a rate that accelerated at older ages. Independent of age, participants who died had a higher BMR compared to those who survived. BMR was a significant risk factor for mortality independent of secular trends in mortality and other well-recognized risk factors for mortality, such as age, body mass index, smoking, white blood cell count, and diabetes. BMR was nonlinearly associated with mortality. The lowest mortality rate was found in the BMR range 31.3-33.9 kcal/m(2)/h. Participants with BMR in the range 33.9-36.4 kcal/m(2)/h and above the threshold of 36.4 kcal/m(2)/h experienced 28% (hazard ratio: 1.28; 95% confidence interval, 1.02-1.61) and 53% (hazard ratio: 1.53; 95% confidence interval, 1.19-1.96) higher mortality risk compared to participants with BMR 31.3-33.9 kcal/m(2)/h. CONCLUSION: We confirm previous findings of an age-related decline of BMR. In our study, a blunted age-related decline in BMR was associated with higher mortality, suggesting that such condition reflects poor health status.

High-density lipoprotein cholesterol and objective measures of lower extremity performance in older nondisabled persons: the InChianti study.

OBJECTIVES: To evaluate the independent association between high-density lipoprotein cholesterol (HDL-C) levels and objective measures of lower extremity performance. DESIGN: Cross-sectional cohort study. SETTING: Community-based. PARTICIPANTS: Eight hundred thirty-six nondisabled women and men aged 65 and older enrolled in the Invecchiare in Chianti study. MEASUREMENTS: Lower extremity performance was assessed using 4-m walking speed at fast pace, 400-m walking speed, and knee extension torque. Fasting HDL-C levels were determined using commercial enzymatic tests. RESULTS: The mean age of participants was 73.7 (65-92), and 55.6% were women. After adjusting for potential confounders (sociodemographic factors, smoking, physical activity, body composition, and clinical conditions including cardiovascular and cerebrovascular disease, inflammatory markers, and serum testosterone) HDL-C levels were significantly associated with knee extension torque in men and women and with 4-m and 400-m walking speed in men. Men in the highest tertile of the HDL-C distribution (>55 mg/dL) had, on average, a three times greater probability of belonging to the best tertile of all indexes of lower extremity performance, including 4-m fast walking speed (odds ratio (OR)=2.57, 95%=confidence interval (CI)=1.07-6.17), 400-m walking speed (OR=3.74, 95% CI=1.20-11.7), and knee extension torque (OR=3.63, 95%=CI 1.41-9.33). Path analysis suggested a direct relationship between HDL-C and knee extension torque. CONCLUSION: In older nondisabled persons, HDL-C levels are highly correlated with knee extension torque and walking speed. Further research should focus on the biological mechanism of this association.