Associations between fibrin D-dimer, markers of inflammation, incident self-reported mobility limitation, and all-cause mortality in older men

Objectives<p></p> To examine the independent relationships between fibrin D-dimer, interleukin 6 (IL-6), C-reactive protein (CRP), and fibrinogen and incident mobility limitation and mortality.<p></p> Design<p></p> Prospective.<p></p> Setting<p></p> General practice in 24 British towns.<p></p> Participants<p></p> Men aged 60 to 79 without prevalent heart failure followed up for an average of 11.5 years (N = 3,925).<p></p> Measurements<p></p> All-cause mortality (n = 1,286) and self-reported mobility disability obtained at examination in 1998 to 2000 and in a postal questionnaire 3 to 5 years later in 2003.<p></p> Results<p></p> High D-dimer (top vs lowest tertile: adjusted odds ratio (aOR) = 1.46, 95% confidence interval = 1.02–2.05) and IL-6 (aOR = 1.43, 95% CI = 1.01–2.02) levels (but not CRP or fibrinogen) were associated with greater incident mobility limitation after adjustment for confounders and prevalent disease status. IL-6, CRP, fibrinogen, and D-dimer were significantly associated with total mortality after adjustment for confounders. Only D-dimer and IL-6 predicted total mortality independent of each other and the other biomarkers. The adjusted hazard ratio (aHR) was 1.16 (95% CI = 1.10–1.22) for a standard deviation increase in log D-dimer and 1.10 (95% CI = 1.04–1.18) for a standard deviation increase in log IL-6. D-dimer was independently related to vascular and nonvascular mortality, and IL-6 was independently related to vascular mortality. Risks of mobility limitation and mortality were greatest in those with a combination of high D-dimer and IL-6 levels.<p></p> Conclusion<p></p> D-dimer and IL-6 are associated with risk of mobility limitation and mortality in older men without heart failure. The findings suggest that coagulation leads to functional decline and mortality s that inflammation does not explain

Haematological variables and risk of future venous thromboembolism in the British Regional Heart Study on men. Combined D-dimer and APTT as a predictive test for thromboembolism?

We examined the associations between haematological and inflammatory variables with future venous thromboembolism (VTE), in 3494 men aged 60–79 years, with no previous history of VTE or myocardial infarction, who were not receiving oral anticoagulants. After a mean follow-up period of 18 years, there were 149 confirmed cases of fatal or non-fatal VTE (deep vein thrombosis and/or pulmonary embolism). Among classical cardiovascular risk factors, only obesity and cigarette smoking were associated with VTE risk. After adjustment for age, obesity and smoking, VTE risk was associated with coagulation factor VIII, factor IX, von Willebrand factor (VWF), activated partial thromboplastin time (APTT), and fibrin D-dimer. Hazard ratios (95% CI) for top to bottom quarters (bottom to top for APTT), were respectively 2.17 (1.37, 3.44), 2.15 (1.30, 3.53), 2.02 (1.27, 3.22), 2.43 (1.47, 4.02) and 3.62 (2.18, 6.08). The 11% of men with both the shortest APTT and highest D-dimer combined had a 5.02 (2.37, 10.62) higher risk of VTE. VTE risk was not associated with fibrinogen, factor VII or activated protein C resistance; full blood count variables or with inflammatory markers, plasma viscosity, C-reactive protein or interleukin-6. The combination of D-dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores

Prospective associations between diet quality, dietary components, and risk of cardiometabolic multimorbidity in older British men

PURPOSE: Cardiometabolic multimorbidity (CMM) is a major public health challenge. This study investigated the prospective relationships between diet quality, dietary components, and risk of CMM in older British men. METHODS: We used data from the British Regional Heart Study of 2873 men aged 60-79 free of myocardial infarction (MI), stroke, and type 2 diabetes (T2D) at baseline. CMM was defined as the coexistence of two or more cardiometabolic diseases, including MI, stroke, and T2D. Sourcing baseline food frequency questionnaire, the Elderly Dietary Index (EDI), which was a diet quality score based on Mediterranean diet and MyPyramid for Older Adults, was generated. Cox proportional hazards regression and multi-state model were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 19.3 years, 891 participants developed first cardiometabolic disease (FCMD), and 109 developed CMM. Cox regression analyses found no significant association between baseline EDI and risk of CMM. However, fish/seafood consumption, a dietary component of the EDI score, was inversely associated with risk of CMM, with HR 0.44 (95% CI 0.26, 0.73) for consuming fish/seafood 1-2 days/week compared to less than 1 day/week after adjustment. Further analyses with multi-state model showed that fish/seafood consumption played a protective role in the transition from FCMD to CMM. CONCLUSIONS: Our study did not find a significant association of baseline EDI with CMM but showed that consuming more fish/seafood per week was associated with a lower risk of transition from FCMD to CMM in older British men

The Relationships of Dentition, Use of Dental Prothesis and Oral Health Problems with Frailty, Disability and Diet Quality: Results from Population-Based Studies of Older Adults from the UK and USA

Objectives: This study examined the relationships of dental status, use and types of dental prothesis and oral health problems, individually and combined, with diet quality, frailty and disability in two population-based studies of older adults. Design: Cross-sectional study. Setting and Participants: Men form the British Regional Heart Study (BRHS) (aged 85±4 years in 2018; n=1013) and Men and Women from the Health, Aging, and Body Composition (HABC) Study (aged 75±3 years in 1998–99; n=1975). Measurements: Physical and dental examinations and questionnaires were collected with data available for dental status, oral problems related to eating, diet quality, Fried frailty phenotype, disability based on mobility limitations, and activities of daily living (ADL). The associations of dental status and oral health problems, individually and combined, with risk of frailty and disability were quantified. The relationship with diet quality was also assessed. Results: In the BRHS, but not HABC Study, impaired natural dentition without the use of dentures was associated with frailty independently. This relationship was only established in the same group in those with oral problems (OR=3.24; 95% CI: 1.30–8.03). In the HABC Study, functional dentition with oral health problems was associated with greater risk of frailty (OR=2.21; 95% CI: 1.18–4.15). In both studies those who wore a full or partial denture in one or more jaw who reported oral problems were more likely to have disability. There was no association with diet quality in these groups. Conclusion: Older adults with impaired dentition even who use dentures who experience self-report oral problems related to eating may be at increased risk of frailty and disability. Further research is needed to establish whether improving oral problems could potentially reduce the occurrence of frailty and disability

Prediction of cardiovascular disease risk by cardiac biomarkers in 2 United Kingdom cohort studies: does utility depend on risk thresholds for treatment?

We tested the predictive ability of cardiac biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T, and midregional pro adrenomedullin for cardiovascular disease (CVD) events using the British Regional Heart Study (BRHS) of men aged 60 to 79 years, and the MIDSPAN Family Study (MFS) of men and women aged 30 to 59 years. They included 3757 and 2226 participants, respectively, and during median 13.0 and 17.3 years follow-up the primary CVD event rates were 16.6 and 5.3 per 1000 patient-years, respectively. In Cox models adjusted for basic classical risk factors, 1 SD increases in log-transformed NT-proBNP, high-sensitivity troponin T, and midregional pro adrenomedullin were generally associated with increased primary CVD risk in both the studies (P<0.006) except midregional pro adrenomedullin in MFS (P=0.10). In BRHS, QRISK2 risk factors yielded a C-index of 0.657, which was improved by 0.017 (P=0.005) by NT-proBNP, but not by other biomarkers. Using 28% 14-year risk as a proxy for 20% 10-year risk, NT-proBNP improved risk classification for primary CVD cases (case net reclassification index, 5.9%; 95% confidence interval, 2.8%–9.2%), but only improved classification of noncases at a 14% 14-year risk threshold (4.6%; 2.9%–6.3%). In MFS, ASSIGN risk factors yielded a C-index of 0.752 for primary CVD; none of the cardiac biomarkers improved the C-index. Improvements in risk classification were only seen using NT-proBNP and high-sensitivity troponin T among cases using the 28% 14-year risk threshold (4.7%; 1.0%–9.2% and 2.6%; 0.0%–5.8%, respectively). In conclusion, the improvement in treatment allocation gained by adding cardiac biomarkers to risk scores seems to depend on the risk threshold chosen for commencing preventative treatments

Influence of neighborhood-level socioeconomic deprivation and individual socioeconomic position on risk of developing type 2 diabetes in older men: a longitudinal analysis in the British Regional Heart Study cohort

INTRODUCTION: Evidence from longitudinal studies on the influence of neighborhood socioeconomic deprivation in older age on the development of type 2 diabetes mellitus (T2DM) is limited. This study investigates the prospective associations of neighborhood-level deprivation and individual socioeconomic position (SEP) with T2DM incidence in older age. RESEARCH DESIGN AND METHODS: The British Regional Heart Study studied 4252 men aged 60-79 years in 1998-2000. Neighborhood-level deprivation was based on the Index of Multiple Deprivation quintiles for participants' 1998-2000 residential postcode. Individual SEP was defined as social class based on longest-held occupation. A cumulative score of individual socioeconomic factors was derived. Incident T2DM cases were ascertained from primary care records; prevalent cases were excluded. Cox proportional hazard models were used to examine the associations. RESULTS: Among 3706 men, 368 incident cases of T2DM were observed over 18 years. The age-adjusted T2DM risk increased from the least deprived quintile to the most deprived: HR per quintile increase 1.14 (95% CI 1.06 to 1.23) (p=0.0005). The age-adjusted T2DM HR in social class V (lowest) versus social class I (highest) was 2.45 (95% CI 1.36 to 4.42) (p=0.001). Both associations attenuated but remained significant on adjustment for other deprivation measures, becoming non-significant on adjustment for body mass index and T2DM family history. T2DM risk increased with cumulative individual adverse socioeconomic factors: HR per point increase 1.14 (95% CI 1.05 to 1.24). CONCLUSIONS: Inequalities in T2DM risk persist in later life, both in relation to neighborhood-level and individual-level socioeconomic factors. Underlying modifiable risk factors continue to need to be addressed in deprived older age populations to reduce disease burden

Associations between inflammation, coagulation, cardiac strain and injury, and subclinical vascular disease with frailty in older men: a cross-sectional study

BACKGROUND: Inflammation, coagulation activation, endothelial dysfunction and subclinical vascular disease are cross-sectionally associated with frailty. Cardiac-specific biomarkers are less-well characterised. We assessed associations between these and frailty, in men with, and without, cardiovascular disease (CVD). METHODS: Cross-sectional analysis of 1096 men without, and 303 with, CVD, aged 71–92, from the British Regional Heart Study. Multinominal logistic regression was performed to examine the associations between frailty status (robust/pre-frail/frail) and, separately, C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), D-dimer, von Willebrand factor (vWF), high-sensitivity cardiac troponin-T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) (all natural log-transformed), and, in men without CVD, carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), adjusted for age, renal function, BMI, social class, smoking, polypharmacy, cognition, multimorbidity and systolic blood pressure. Explanatory variables with p < 0.05 were carried forward into mutually-adjusted analysis. RESULTS: In men without CVD, higher CRP, IL-6, vWF, tPA, hs-cTnT, NT-proBNP, cfPWV, and lower DC were significantly associated with frailty; mutually-adjusted, log IL-6 (OR for frailty = 2.02, 95%CI 1.38–2.95), log hs-cTnT (OR = 1.95, 95%CI 1.24–3.05) and DC (OR = 0.92, 95%CI 0.86–0.99) retained associations. In men with CVD, higher CRP, IL-6, and hs-cTnT, but not vWF, tPA, NT-proBNP or D-dimer, were significantly associated with frailty; mutually-adjusted, log hs-cTnT (OR 3.82, 95%CI 1.84–7.95) retained a significant association. CONCLUSIONS: In older men, biomarkers of myocardial injury are associated with frailty. Inflammation is associated with frailty in men without CVD. Carotid artery stiffness is associated with frailty in men without CVD, independently of these biomarkers

Oral health problems and risk of incident disability in two studies of older adults in the United Kingdom and the United States

Background: Preventing oral health problems can be crucial for maintaining physical independence in older adults. We aimed to examine the associations of a range of oral health problems with incidence of disability in older adults. Methods: We used prospective data from the British Regional Health Study (BRHS) (N = 2147, 71–92 years), and the Health, Aging and Body Composition (HABC) study (USA) (N = 3075, 71–80 years). Oral health measures included tooth loss, periodontal disease, self-rated oral health, and self-reported dry mouth. Participants were followed for onset of disability over a follow-up period of 3 years. Onset of disability was assessed through new cases of mobility limitations, activities of daily living (ADL), and instrumental activities of daily living (IADL). Logistic regression was performed to calculate the odds of incident disability. Results: In the BRHS, tooth loss was associated with greater odds of mobility limitations and ADL difficulties. Periodontal disease was associated with greater incidence of mobility limitations. Self-report of ≥3 dry mouth symptoms was associated with increased odds of incident mobility limitations and ADL difficulties (OR = 2.08, 95% CI 1.27–3.42; OR = 1.73, 95% CI 1.03–2.90). Fair/poor self-rated oral health was associated with greater incidence of IADL difficulties. In the HABC study, complete tooth loss was associated with greater incidence of mobility limitations (OR = 1.86, 95% CI 1.13–3.06), and fair/poor self-rated oral health was associated with increased odds of incident ADL difficulties (OR = 1.42, 95% CI 1.04–1.94). Conclusions: Oral health problems in older adults, particularly tooth loss, self-reported dry mouth and self-rated oral health were associated with greater incidence of disability. Poor oral health plays a potentially important role in the development of disability in older populations, which in turn is an essential part of quality of life and healthy aging