The shared ancestry between the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles using haplotype sharing trees and HAPTK.

The C9orf72 hexanucleotide repeat expansion (HRE) is a common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The inheritance is autosomal dominant, but a high proportion of subjects with the mutation are simplex cases. One possible explanation is de novo expansions of unstable intermediate-length alleles (IAs). Using haplotype sharing trees (HSTs) with the haplotype analysis tool kit (HAPTK), we derived majority-based ancestral haplotypes of HRE samples and discovered that IAs containing ≥18-20 repeats share large haplotypes in common with the HRE. Using HSTs of HRE and IA samples, we demonstrate that the longer IA haplotypes are largely indistinguishable from HRE haplotypes and that several ≥18-20 IA haplotypes share over 5 Mb (>600 markers) haplotypes in common with the HRE haplotypes. These analysis tools allow physical understanding of the haplotype blocks shared with the majority-based ancestral haplotype. Our results demonstrate that the haplotypes with longer IAs belong to the same pool of haplotypes as the HRE and suggest that longer IAs represent potential premutation alleles.

Clinical trials in older people.

Randomised controlled trials (RCTs) usually provide the best evidence for treatments and management. Historically, older people have often been excluded from clinical medication trials due to age, multimorbidity and disabilities. The situation is improving, but still the external validity of many trials may be questioned. Individuals participating in trials are generally less complex than many patients seen in geriatric clinics. Recruitment and retention of older participants are particular challenges in clinical trials. Multiple channels are needed for successful recruitment, and especially individuals experiencing frailty, multimorbidity and disabilities require support to participate. Cognitive decline is common, and often proxies are needed to sign informed consent forms. Older people may fall ill or become tired during the trial, and therefore, special support and empathic study personnel are necessary for the successful retention of participants. Besides the risk of participants dropping out, several other pitfalls may result in underestimating or overestimating the intervention effects. In nonpharmacological trials, imperfect blinding is often unavoidable. Interventions must be designed intensively and be long enough to reveal differences between the intervention and control groups, as control participants must still receive the best normal care available. Outcome measures should be relevant to older people, sensitive to change and targeted to the specific population in the trial. Missing values in measurements are common and should be accounted for when designing the trial. Despite the obstacles, RCTs in geriatrics must be promoted. Reliable evidence is needed for the successful treatment, management and care of older people.

Plasma ceramides independently predict all-cause mortality in men aged 85.

BACKGROUND: assessing cardiovascular and mortality risk with conventional biomarkers is challenging in oldest-old due to multimorbidity and polypharmacy. Ceramides are bioactive lipids shown to predict mortality in late middle-aged cohorts. OBJECTIVE: to assess whether plasma ceramides have independent prognostic value for mortality among oldest-old (85+). DESIGN: longitudinal cohort study (Helsinki Businessmen Study, HBS) with a 3.5-year follow-up. SETTING AND SUBJECTS: survivors of HBS (125 men born in 1919-1934) visited the clinic for laboratory and clinical examination. METHODS: functional status including physical (short physical performance battery) and Montreal Cognitive Assessment (MoCA) cognitive performance was assessed and laboratory examinations included a large set of biomarkers. Plasma ceramide concentration (Cer(d18:1/16:0)) was measured using a targeted liquid chromatography-tandem mass spectrometry assay. Mortality was retrieved from national registers. RESULTS: median age was 88 years, two-thirds had multimorbidity and 59% were on statin treatment. During the follow-up, 22 (18%) men died. In a model adjusted for variables associated with mortality in the whole cohort at P < 0.20 (log glucose, SPPB, MoCA and statin use), Cer(d18:1/16:0) as a continuous trait was associated with increased mortality: hazard ratio (HR) per 1 SD 1.64 (95% confidence interval [CI] 1.23-2.18). Compared with the bottom tertile of Cer(d18:1/16:0), HR of mortality was 5.44-fold (95% CI 1.17-25.3) in the top tertile. CONCLUSIONS: these data raise the hypothesis that plasma ceramide concentrations and especially Cer(d18:1/1:60) may offer a clinically useful biomarker to evaluate prognosis in very old age. Such biomarkers are needed for geriatrics, where multimorbidity and pharmacotherapies, such as statins are prevalent hampering assessment of prognosis using conventional methods.

Retirement as a predictor of physical functioning trajectories among older businessmen.

BACKGROUND: Associations between retirement characteristics and consequent physical functioning (PF) are poorly understood, particularly in higher socioeconomic groups, where postponing retirement has had both positive and negative implications for PF. METHODS: Multiple assessments of PF, the first of which at the mean age of 73.3 years, were performed on 1709 men who were retired business executives and managers, using the RAND-36/SF-36 instrument, between 2000 and 2010. Questionnaire data on retirement age and type of pension was gathered in 2000. Five distinct PF trajectories were created using latent growth mixture modelling. Mortality- and covariate-adjusted multinomial regression models were used to estimate multinomial Odds Ratios (mOR) on the association between retirement characteristics and PF trajectories. RESULTS: A one-year increase in retirement age was associated with decreased likelihood of being classified in the 'consistently low' (fully adjusted mOR = 0.82; 95%CI = 0.70, 0.97; P = 0.007), 'intermediate and declining' (mOR = 0.89; 95%CI = 0.83, 0.96; P = 0.002), and 'high and declining' (mOR = 0.92; 95%CI = 0.87, 0.98; P = 0.006) trajectories, relative to the 'intact' PF trajectory. Compared to old age pensioners, disability pensioners were more likely to be classified in the 'consistently low' (mOR = 23.77; 95% CI 2.13, 265.04; P = 0.010), 'intermediate and declining' (mOR = 8.24; 95%CI = 2.58, 26.35; P < 0.001), and 'high and declining' (mOR = 2.71; 95%CI = 1.17, 6.28; P = 0.020) PF trajectories, relative to the 'intact' PF trajectory. CONCLUSIONS: Among executives and managers, older age at retirement was associated with better trajectories of PF in old age. Compared to old age pensioners, those transitioning into disability and early old age pensions were at risk of having consistently lower PF in old age.

Determinants of a sense of insecurity among home-dwelling older people.

Aims: A sense of insecurity may have an impact on older people's well-being and their courage to engage actively in meaningful activities. Studies on a sense of insecurity among older people are scarce. The aim of this study was to determine the extent to which home-dwelling older adults perceive their life as being insecure and how a sense of insecurity is associated with their health, functional status, active social engagement, well-being and perceptions of the societal treatment of older people. Methods: This study is part of the Helsinki Aging Study, a cohort study ongoing since 1989. Data were collected using a postal questionnaire that was mailed in 2019 to a random sample of home-dwelling older people ⩾75 years of age living in Helsinki (N=2917; response rate 74%). The questionnaire inquired about the respondents' sense of security/insecurity, and they were subcategorised into those feeling secure and those feeling insecure based on their answers. Results: Seven per cent of respondents felt insecure in their lives. In a stepwise logistic regression analysis, loneliness, living alone and perceived poor societal treatment of older people were associated with a sense of insecurity, while having good self-rated health, having children and meeting friends at least weekly were associated with lower odds of insecurity. Conclusions: Our findings highlight the importance of recognising and combating loneliness, social isolation and societal ageism in order to reduce insecurity among older people and to support their active engagement in life.

Association of plasma gelsolin with frailty phenotype and mortality among octogenarian community-dwelling men: a cohort study.

BACKGROUND: Biomarkers are needed for frailty, a common phenotype often associated with muscle loss in older people. Plasma gelsolin (pGSN) is a protein largely synthesized and secreted by skeletal muscle. AIMS: To investigate whether pGSN could be a biomarker of the frailty phenotype and predict mortality. METHODS: A homogenous cohort of males (born 1919-1934, baseline n = 3490) has been followed since the 1960s. In 2010/11, frailty phenotypes by modified Fried criteria were assessed. pGSN was measured in a convenience subset (n = 469, mean age 83) and re-measured in survivors (n = 127) in 2017. Mortality through December 31, 2018 was retrieved from national registers. Regression models were used for analyses. RESULTS: Of 469 males, 152 (32.4%) were robust, 284 (60.6%) prefrail, and 33 (7.0%) frail in 2010/11. There was a graded (p = 0.018) association between pGSN (mean 58.1 ug/mL, SD 9.3) and frailty. After multivariable adjustment, higher pGSN levels were associated with lower odds of having contemporaneous phenotypic prefrailty (OR per 1 SD 0.73, 95% CI 0.58-0.92) and frailty (OR per 1 SD 0.70, 95% CI 0.44-1.11). By 2018, 179 males (38.2%) had died, and higher baseline pGSN predicted a lower 7-year mortality rate (HR per 1 SD 0.85, 95% CI 0.72-1.00). pGSN concentrations in 2010/11 and 2017 were correlated (n = 127, r = 0.34, p < 0.001). DISCUSSION: Higher baseline pGSN concentrations were associated with a persistently robust phenotype and lower mortality rate over 7 years in a cohort of octogenarian males with high socioeconomic status and may be a promising laboratory biomarker for the development of a frailty phenotype.

Monetary value of informal caregiving in dementia from a societal perspective.

BACKGROUND: Dementia is a condition which results in a high cost of care, a significant proportion of which is the cost associated with informal care. In previous studies, informal caregiving has been challenging to assess due to difficulties in estimating the true time spent on caregiving work and how to value caregivers' time. The aim of this study was to compare the costs of dementia among patients living alone and among those living with a caregiver to show the monetary value of informal caregiving from a societal perspective. METHODS: Data from our four dementia trials using the same measures were combined, allowing the inclusion of 604 participants. Participants were followed up for 2 years or until death for their use of health and social services. Use of all services was retrieved from medical/social records. We also included the costs of lost productivity of those caregivers who were not retired. RESULTS: The total mean cost of services and lost productivity was €22,068/person-year (pyrs). Participants living alone had a mean cost of €45,156/pyrs, whereas those living with a spouse had a mean cost of €16,416/pyrs (mean cost ratio 2.99, 95% confidence interval 2.64-3.39). Participants living alone and having <15 Mini-Mental State Examination points had higher costs than people with dementia in institutional care. CONCLUSIONS: Detailed data of service use and characteristics of people with dementia showed that from a societal perspective, living alone is a very strong determinant of service use in dementia. Informal caregivers do invaluable work for society.

Associations of coffee drinking with physical performance in the oldest-old community-dwelling men The Helsinki Businessmen Study (HBS).

BACKGROUND: Habitual coffee drinking has been associated with lower risk of various chronic diseases linked to poor physical performance. OBJECTIVE: We explored cross-sectional associations between coffee consumption and physical performance among oldest-old community-dwelling men in the Helsinki Businessmen Study (HBS). METHODS: A random sample of HBS survivors (n = 126, mean age 87 years) attended a clinic visit in 2017/2018, including measurements of body composition, physical performance [Short Physical Performance Battery (SPPB)], and cognition. Coffee consumption was retrieved from 3-day food diaries. RESULTS: Coffee consumption was positively associated with higher gait speed (p = 0.003), SPPB score (p = 0.035), and chair rise points (p = 0.043). Association of coffee with gait speed remained after adjustment for age, waist circumference, physical activity, pulse rate, and high-sensitivity C-reactive protein. CONCLUSION: Higher coffee consumption was independently associated with better physical performance reflected as faster gait speed in oldest-old men.

Statin treatment, phenotypic frailty and mortality among community-dwelling octogenarian men: the HBS cohort.

BACKGROUND: statin treatment has increased also among people aged 80 years and over, but adverse effects potentially promoting frailty and loss of resilience are frequent concerns. METHODS: in the Helsinki Businessmen Study, men born in 1919-34 (original n = 3,490) have been followed up since the 1960s. In 2011, a random subcohort of home-living survivors (n = 525) was assessed using questionnaires and clinical (including identification of phenotypic frailty) and laboratory examinations. A 7-year mortality follow-up ensued. RESULTS: we compared 259 current statin users (median age 82 years, interquartile range 80-85 years) with 266 non-users (83; 80-86 years). Statin users had significantly more multimorbidity than non-users (prevalencies 72.1% and 50.4%, respectively, P < 0.0001) and worse glucose status than non-users (prevalencies of diabetes 19.0% and 9.4%, respectively, P = 0.0008). However, there was no difference in phenotypic frailty (10.7% versus 11.2%, P = 0.27), and statin users had higher plasma prealbumin level than non-users (mean levels 257.9 and 246.3 mg/L, respectively, P = 0.034 adjusted for age, body mass index and C-reactive protein) implying better nutritional status. Despite morbidity difference, age-adjusted 7-year mortality was not different between the two groups (98 and 103 men among users and non-users of statins, respectively, hazard ratio 0.96, 95% confidence interval 0.72-1.30). CONCLUSIONS: our study suggests that male octogenarian statin users preserved resilience and survival despite multimorbidity, and this may be associated with better nutritional status among statin users.

Future Perspectives on the Role of Frailty in Cardiovascular Diseases.

Frailty is a clinical concept which is gaining increased momentum not only in geriatrics, but in all specialties treating adult patients. In these Future Perspectives, the following roles of frailty in the field of cardiovascular diseases (CVD) will be discussed as a narrative review: (1) Frailty as an adjunct to assess CVD patients in addition to traditional risk scores; (2) bidirectional relationship between frailty and CVD; (3) widening the scope of endpoints in CVD trials-inclusion of frailty; (4) finally, the relationship between geriatrics and cardiology will be shortly discussed.

Impaired breathing, sleeping, vitality, and depression, and negative impact of L-T4 treatment characterize health-related quality of life in older people with stable CVD.

BACKGROUND: Cardiovascular disease (CVD) and thyroid dysfunction are common in older people, but little is known about how they affect health-related quality of life (HRQoL). METHODS: We assessed HRQoL with the 15D instrument in 329 home-dwelling patients aged ≥ 75 years with stable CVD and compared the results to those of an age- and gender-matched general population (n = 103). We also studied the impact of age, BMI, number of medications, thyroid-stimulating hormone (TSH) concentration, levothyroxine (L-T4) substitution and Mini-Mental State Examination (MMSE) on HRQoL. RESULTS: Overall HRQoL was impaired in older people with stable CVD (mean 15D score 0.777 vs 0.801, p = 0.001), and also on single dimensions of breathing, sleeping, discomfort and symptoms, distress, vitality (all p < 0.001), and depression (p = 0.016) compared to the age- and gender-matched general population. Furthermore, in the patients, L-T4 substitution associated with impaired sleeping (p = 0.018) and sexual activity (p = 0.030). Moreover, MMSE points, number of medications used, age (all p < 0.001) and BMI (p = 0.009) predicted impaired HRQoL. CONCLUSIONS: Older people with stable CVD are characterized by impaired HRQoL compared to age- and gender-matched controls. We demonstrate that this is the consequence of impaired breathing, sleeping, discomfort and symptoms, distress, vitality, and depression. L-T4 substitution has a negative impact on HRQoL in old patients with stable CVD. MMSE score, number of medications, age and BMI predict worse HRQoL.

The associations of body mass index, bioimpedance spectroscopy-based calf intracellular resistance, single-frequency bioimpedance analysis and physical performance of older people.

BACKGROUND: Bioimpedance skeletal muscle indices (SMI) are used as a surrogate for skeletal muscle mass, but their associations with physical functioning and obesity need further evaluation. AIMS: To compare the associations of body mass index (BMI), bioimpedance spectroscopy-based calf intracellular resistance (Cri-SMI), and single-frequency bioimpedance analysis (SF-SMI) indices with physical performance and the functioning of community-dwelling older people at risk of or already suffering from sarcopenia. METHODS: Pre-intervention measurements of the screened subjects and the participants of the Porvoo sarcopenia trial (N = 428) were taken. Cri-SMI, whole-body SF-SMI, and BMI were related to hand-grip strength, walking speed, short physical performance battery (SPPB), and the physical component of the RAND-36. RESULTS: Among the older people (aged 75-96), Cri-SMI correlated inversely with age (men r = - 0.113, p < 0.001; women r = - 0.287, p < 0.001), but positively with SPPB (r = 0.241, p < 0.001) and the physical component of the RAND-36 (r = 0.114, p = 0.024), whereas BMI was inversely associated with SPPB (r = - 0.133, p < 0.001) and RAND-36 (r = - 0.286, p < 0.001). After controlling for age, gender, and comorbidity, one unit of Cri-SMI (cm2/Ω) was associated with a 3.3-fold probability of good physical performance (SPPB ≥ 9 points, OR = 3.28, p < 0.001) and one unit of BMI (kg/m2) decreased the respective probability 4% (OR= 0.96, p = 0.065). Physical inactivity partly explained the negative association of BMI. When Cri-SMI and BMI were controlled for, a 1% difference in Cri-SMI was associated with a 0.7% (p < 0.001) higher probability of good performance, the respective figure being - 2.2% (p = 0.004) for BMI. The associations of SF-SMI with physical functioning indices were insignificant. CONCLUSIONS: Independent of each other, Cri-SMI was positively and BMI was inversely associated with the physical performance and functioning of community-dwelling older people who were at risk of or already suffering from sarcopenia. We found no association between SF-SMI and physical functioning.

Major cardiovascular disease (CVD) risk factors in midlife and extreme longevity.

BACKGROUND: The studies on the association of various midlife risk factors with reaching 90 years or more are scarce. We studied this association in a socioeconomically homogenous cohort of businessmen. METHODS: The study consists of men (n = 970) from the Helsinki Businessmen Study cohort (born 1919-1928). Five major cardiovascular disease (CVD) risk factors (smoking, BMI, blood pressure, serum lipids, fasting glucose), consumption of alcohol and coffee, self-rated health and self-rated fitness, were assessed in 1974, at an average age of 50 years. The number of major risk factors was tested as a risk burden. The Charlson Comorbidity Index and the RAND-36 (SF-36) Physical and Mental health summary scores were calculated from surveys in year 2000, at age of 73 years. Mortality dates were retrieved through 31 March 2018 from the Population Information System of Finland. RESULTS: 244 men survived to the age of 90 representing 25.2% of the study cohort. The survivors had less risk factor burden in midlife, and less morbidity and higher physical health summary score in 2000. Of those with five major risk factors only 7% survived up to 90 years, whereas 51% of those without any risk factors reached that age. Single risk factors reducing odds of reaching 90 years were smoking (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.34-0.67), glucose (0.66, 0.49-0.88), BMI (0.63, 0.46-0.86), and cholesterol (0.71, 0.53-0.96). CONCLUSION: Lack of five major CVD risk factors in midlife strongly increased odds of reaching 90 years of age and also predicted factors related to successful ageing in late life.

Sitagliptin does not reduce the risk of cardiovascular death or hospitalization for heart failure following myocardial infarction in patients with diabetes: observations from TECOS.

BACKGROUND: To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). METHODS: TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. RESULTS: During TECOS, 616 participants had ≥ 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. CONCLUSIONS: In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205.

Role of Statin Therapy in Primary Prevention of Cardiovascular Disease in Elderly Patients.

PURPOSE OF REVIEW: Hypercholesterolemia and statin treatment are nowadays common among people older than 75 years, but clinical heterogeneity in this increasing age group is wide, and treatment decisions may differ from those in younger patients. Aim is to discuss the presentation, modifying factors, and treatment decisions of hypercholesterolemia (usually with statins) in older persons and focusing on primary prevention. RECENT FINDINGS: There are no randomized controlled trials in persons older than 80 years at baseline. Randomized controlled trial findings in younger patients and 75+ subgroups and in observational studies support treatment in secondary prevention of atherosclerotic cardiovascular disease (ASCVD), but trial evidence in primary prevention is less clear. Available data do not imply specific harms in older patients, and, therefore, also, judicious primary prevention is possible. However, persons older than 75 years are biologically a very heterogeneous group with frequent frailty, comorbid conditions, and multiple concomitant drugs. All these, as well as personal preferences, must be taken into account in treatment decisions. Statin treatment is only one way to prevent ASCVD in older people. Treatment of hypercholesterolemia should be started far before 75-80 years, and there is no need to discontinue statin treatment due to chronological age alone. After 75 years, treatment should be started in patients with ASCVD and judiciously in primary prevention. Like all prevention, statin treatment should be discontinued when palliative treatment is started. Ongoing and planned trials in 70+ individuals will give more information about primary prevention in older persons.

Midlife predictors of active and healthy aging (AHA) among older businessmen.

BACKGROUND: Active and healthy aging (AHA) is an important phenomenon in aging societies. AIMS: Our aim was to investigate midlife predictors of AHA in a socioeconomically homogenous male cohort. METHODS: In 2010, AHA was defined in the Helsinki Businessmen Study (men born in 1919-1934) with six criteria: (1) being alive, (2) responding to the mailed survey, (3) no reported cognitive problems, (4) feeling of happiness, (5) no difficulties in activities of daily living (ADL), and (6) no significant chronic diseases. Midlife factors were assessed in 1974 (n = 1759, mean age 47 years). Of the survivors in 2010 (n = 839), 10.0% (n = 84) fulfilled all AHA criteria, whilst 13.7% (n = 115) had chronic diseases but fulfilled other five criteria. Midlife predictors of AHA were analyzed with logistic models. RESULTS: Of the midlife factors, smoking [Odds ratio (OR) 0.44, 95% confidence interval (CI) 0.25-0.77], higher body mass index (BMI) (OR 0.75, 0.59-0.96), and higher total cholesterol (OR 0.76, 0.60-0.97) prevented significantly full AHA criteria, whereas higher self-rated health (SRH) (OR 1.73, 1.07-2.80) predicted significantly of fulfilling all AHA criteria. Midlife smoking (OR 0.87, 0.84-0.91), higher BMI (OR 0.73, 0.61-0.86), and higher alcohol consumption (OR 0.73, 0.60-0.90) prevented significantly of fulfilling the five AHA criteria with chronic diseases, and higher SRH (OR 1.90, 1.37-2.63) predicted significantly the five AHA criteria (chronic diseases present). DISCUSSION: Our study suggests that midlife factors, especially good SRH and low levels of cardiovascular risk factors, are associated with AHA. CONCLUSIONS: The study emphasizes the importance of life-course predictors of healthy aging.

Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus: International Insights From the TECOS Trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin).

BACKGROUND: Intensive risk factor modification significantly improves outcomes for patients with diabetes mellitus and cardiovascular disease. However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown. METHODS: Attainment of 5 secondary prevention parameters-aspirin use, lipid control (low-density lipoprotein cholesterol <70 mg/dL or statin therapy), blood pressure control (<140 mm Hg systolic, <90 mm Hg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and nonsmoking status-was evaluated among 13 616 patients from 38 countries with diabetes mellitus and known cardiovascular disease at entry into TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Logistic regression was used to evaluate the association between individual and regional factors and secondary prevention achievement at baseline. Cox proportional hazards regression analysis was used to determine the association between baseline secondary prevention achievement and cardiovascular death, myocardial infarction, or stroke. RESULTS: Overall, 29.9% of patients with diabetes mellitus and cardiovascular disease achieved all 5 secondary prevention parameters at baseline, although 71.8% achieved at least 4 parameters. North America had the highest proportion (41.2%), whereas Western Europe, Eastern Europe, and Latin America had proportions of ≈25%. Individually, blood pressure control (57.9%) had the lowest overall attainment, whereas nonsmoking status had the highest (89%). Over a median 3.0 years of follow-up, a higher baseline secondary prevention score was associated with improved outcomes in a step-wise graded relationship (adjusted hazard ratio, 0.60; 95% confidence interval, 0.47-0.77 for those patients achieving all 5 measures versus those achieving ≤2). CONCLUSIONS: In an international trial population, significant opportunities exist to improve the quality of cardiovascular secondary prevention care among patients with diabetes mellitus and cardiovascular disease, which in turn could lead to reduced risk of downstream cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205.

Alcohol consumption in midlife and old age and risk of frailty: Alcohol paradox in a 30-year follow-up study.

Background: alcohol consumption has many harmful health effects, but also benefits of moderate consumption on frailty have been reported. We examined this relationship longitudinally from midlife to old age. Methods: data of reported alcohol consumption in midlife (year 1974) and in old age (years 2000 and 2003) were available of a socioeconomically homogenous sample of 2360 men (born 1919-34, the Helsinki Businessmen Study). Alcohol consumption was divided into zero (N = 131 at baseline), light (1-98 g/week, N = 920), moderate (99-196, N = 593), and high consumption (>196, n = 716). Incidence of phenotypic frailty and prefrailty was assessed in 2000 and 2003. Alcohol consumption (reference 1-98 g/week, adjusted for age, body mass index and smoking) was related to frailty both longitudinally (from 1974 to 2000, and from 2000 to 2003) and cross-sectionally in 2000 and 2003. Results: during a 30-year follow-up, high consumption clearly decreased whereas lighter consumption remained stable. High consumption in midlife predicted both frailty (odds ratio = 1.61, 95% confidence interval = 1.01-2.56) and prefrailty (1.42; 1.06-1.92) in 2000, association with zero and moderate consumption was insignificant. Cross-sectionally in 2000, both zero (2.08; 1.17-3.68) and high consumption (1.83; 1.07-3.13) were associated with frailty, while in 2003 only zero consumption showed this association (2.47; 1.25-4.88). Conclusion: the relationship between alcohol and frailty is a paradox during the life course. High, not zero, consumption in midlife predicts old age frailty, while zero consumption in old age is associated with frailty, probably reflecting reverse causality.

Association of midlife value priorities with health-related quality of life, frailty and mortality among older men: a 26-year follow-up of the Helsinki Businessmen Study (HBS).

PURPOSE: Personal values influence behavior and decision making, but their long-term associations with health-related quality of life (HRQoL), frailty, and mortality are less clear. We studied these associations from midlife to old age in a 26-year follow-up of the Helsinki Businessmen Study (HBS) cohort. METHODS: In 1974, 1320 clinically healthy men (born 1919-1934) reported in a 12-item questionnaire their personal values. In 2000, a mailed questionnaire, including assessment of HRQoL with RAND-36 (SF-36) instrument, was sent to survivors, and 1025 men responded. In 2000, the presence of phenotypic frailty was assessed using modified Fried criteria including indicators of shrinking, physical weakness, exhaustion, and physical inactivity. Mortality through December 31, 2000 was verified from national registries. RESULTS: Using a factor analysis, the data of the 12-item questionnaire of personal values were loaded in 3 factors: valuing health ("Health"), enjoyable and varying life ("Enjoyment"), and comfort and work-oriented life ("Work-life-balance"). Adjusted for age, we found a significant positive association between valuing "Health" in midlife and RAND-36 domains of Physical functioning (p = .032) and Vitality (p = .005) in old age. "Health" also predicted less frailty (p = .008), and "Enjoyment" was associated with higher mortality (p = .017). CONCLUSIONS: Value priorities of men assessed in midlife had long-term associations with HRQoL and frailty in old age, and they may also predict mortality.