Correlates of frailty phenotype and frailty index and their associations with clinical outcomes.

OBJECTIVES: Frailty is a predictor of adverse health outcomes and can be measured across the life course, including among people living with HIV. The purpose of this study was to examine two commonly used measures of frailty - the frailty index (FI) and frailty phenotype - to assess common characteristics and to describe associations with multimorbidity, falls, and disability in people aging with HIV. METHODS: This was a cross-sectional observational study including 482 consecutive HIV-infected patients (mean age 53.9 ± SD 6.9 years; 75% male) attending the multidisciplinary metabolic clinic at the University of Modena, Italy. Frailty was measured with the frailty phenotype and a 37-item FI. RESULTS: The mean FI score was 0.28±0.1 and frailty phenotype categories were: 3.1% frail, 51.9% pre-frail, and 45% robust. The duration of antiretroviral therapy was significantly different across levels of frailty as measured by both frailty tools (P < 0.01), but the nadir CD4 count was only significant for the FI (P = 0.01); current CD4 count was not significantly different across frailty levels using either tool. Both frailty measures were associated with multimorbidity; the FI was associated with Instrumental Activities of Daily Living impairment and falls history, whereas the frailty phenotype was not. CONCLUSIONS: The frailty phenotype and the FI demonstrated similar characteristics in patients at a tertiary-level HIV clinic. The FI had a stronger association with age, nadir CD4 count, comorbidities, falls, and disability. Integrating frailty assessments in clinical practice will be crucial for the development of interventions in age-related conditions, including disability and falls, in older persons living with HIV.

Body mass index versus waist circumference as predictors of mortality in Canadian adults.

BACKGROUND: Elevated body mass index (BMI) and waist circumference (WC) are associated with increased mortality risk, but it is unclear which anthropometric measurement most highly relates to mortality. We examined single and combined associations between BMI, WC, waist-hip ratio (WHR) and all-cause, cardiovascular disease (CVD) and cancer mortality. METHODS: We used Cox proportional hazard regression models to estimate relative risks of all-cause, CVD and cancer mortality in 8061 adults (aged 18-74 years) in the Canadian Heart Health Follow-Up Study (1986-2004). Models controlled for age, sex, exam year, smoking, alcohol use and education. RESULTS: There were 887 deaths over a mean 13 (SD 3.1) years follow-up. Increased risk of death from all-causes, CVD and cancer were associated with elevated BMI, WC and WHR (P<0.05). Risk of death was consistently higher from elevated WC versus BMI or WHR. Ascending tertiles of each anthropometric measure predicted increased CVD mortality risk. In contrast, all-cause mortality risk was only predicted by ascending WC and WHR tertiles and cancer mortality risk by ascending WC tertiles. Higher risk of all-cause death was associated with WC in overweight and obese adults and with WHR in obese adults. Compared with non-obese adults with a low WC, adults with high WC had higher all-cause mortality risk regardless of BMI status. CONCLUSION: [corrected] BMI and WC predicted higher all-cause and cause-specific mortality, and WC predicted the highest risk for death overall and among overweight and obese adults. Elevated WC has clinical significance in predicting mortality risk beyond BMI.

Role of the fractalkine receptor CX3CR1 polymorphisms V249I and T280M as risk factors for early-onset coronary artery disease in patients with no classic risk factors.

OBJECTIVES: CX3CR1 is a monocyte chemokine receptor and adhesion molecule. Two CX3CR1 mutations, V249I and T280M, reportedly decrease coronary artery disease (CAD) risk independent of established risk factors. An I249 protective effect is attributed to reducing CX3CR1 binding to fractalkine, its ligand. MATERIAL AND METHODS: We examined the frequencies of V249I and T280M among early-onset CAD patients (G1; n = 149; <50 years), late-onset CAD patients (G2; n = 150; >65 years) and healthy controls (HC; n = 149, 47-93 years) without known CAD risk factors. We compared plasma total cholesterol (TC)/high density lipoprotein-C (HDL-C) and apolipoprotein B (APOB)/apolipoprotein AI (APOAI) ratios among the groups and mutation carriers and non-carriers, and the prevalence of the mutations in G1 and G2 patients with multiple coronary vessel disease (MVD) and myocardial infarction (MI). RESULTS: G1 patients had non-significantly lower frequencies of I249 versus (vs.) G2 or controls (G1; 51 %, G2: 61 %, controls: 58 %, p = 0.19), with no difference in T280M (p = 0.8). TC/HDL-C and APOB/APOAI ratios were significantly higher in G1 patients vs. G2 and controls (p<0.0001) independently of either mutation. More G2 patients had MVD than younger ones (p<0.0001); however, more G1 patients were homozygous for V249 compared to G2 patients, who more often had the I249 allele (p<0.02). There was no such association with T280M (p = 0.38). Although more G1 patients had MI, this was not mutation related. CONCLUSIONS: There were significantly higher lipid ratios in G1 compared to G2 and HC (G1>G2>HC), but not in mutation prevalence. I249 mutation was associated with MVD in older patients, while V249 homozygosity was associated with the early-onset CAD. Neither allele affected MI or lipid levels.

Oral contraceptive use and bone mineral density in premenopausal women: cross-sectional, population-based data from the Canadian Multicentre Osteoporosis Study.

BACKGROUND: Positive and negative effects on bone mineral density (BMD) have been described as a result of the premenopausal use of oral contraceptives (OCs); increased fracture rates have also been reported. This study assessed the relation between OC use and BMD in a population-based, 9-centre, national sample of women aged 25-45 years. METHODS: Premenopausal women who had been enrolled in the Canadian Multicentre Osteoporosis Study were classified as having ever been OC users (> or = 3 months) or as having never been OC users (0 to < 3 months). Data were obtained through extensive questionnaires and measuring of participants' weight, height and the BMD of lumbar vertebrae and the proximal femur. RESULTS: Of the sample of 524 women, whose mean age was 36.3 (standard deviation [SD] 5.9) years, 454 had used OCs; their mean age when they started using OCs was 19.8 (SD 3.5) years and the mean duration of use was 6.8 (SD 4.8) years. Women who had ever and those who had never used OCs showed no differences in age, age at menarche, parity, current calcium intake, exercise, body mass index (BMI), education, past irregular cycles or amenorrhea. OC users reported more alcohol and cigarette use and more use of medications to create regular cycles. Mean BMD values (adjusted for age, BMI and height) were 0.02-0.04 g/cm2 (that is, 2.3%-3.7%) lower in OC users, and were significantly lower in the spine and trochanter. The BMD of the spine in OC users was 1.03 (SD 0.12) g/cm2 versus 1.07 (SD 0.12) g/cm2 (95% confidence interval [CI] of difference -0.07 to -0.001) in those who had never used OCs. BMD was neither related to the duration of OC use nor to gynecological age at first use. Current and past users had similar BMD values. INTERPRETATION: National, population-based data show lower BMD values for the trochanter and spine in premenopausal women who have used OCs compared with those who have never used OCs.

Relationship of the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and early-onset coronary artery disease.

BACKGROUND: The Glu298Asp polymorphism of endothelial nitric oxide synthase (eNOS) gene has been associated with coronary artery disease (CAD) in some but not all studies. To determine the impact of the mutant Asp298 eNOS allele on the development of premature CAD, we examined the prevalence of this mutation in patients with early-onset CAD compared with those manifesting CAD later in life. If this mutation confers an increased risk of premature CAD, we hypothesized that the frequency of the homozygous mutation (Asp298Asp298) would be greater among the younger patient group. METHODS: A total of 299 patients with a history of myocardial infarction (MI) or angina pectoris plus angiographically documented CAD were studied. Patients were divided into 2 groups: group 1 (149 patients) included patients with CAD before the age of 50 years and group 2 (150 patients) included patients with a first presentation of CAD at >65 years old. Prevalence of eNOS Glu298 and Asp298 alleles was assessed by molecular analysis and compared for the 2 groups. RESULTS: There was no significant difference in the frequency of the mutant Asp298 allele between the 2 groups (G1: 42% vs G2: 42.7%, P =.79). The frequencies of the Glu298Glu298, Glu298Asp298, and Asp298Asp298 genotypes were similar in both groups (34.9%, 46.3%, and 18.8% for G1 and 29.3%, 56%, and 14.7% for G2, respectively, P =.29). CONCLUSIONS: Our study does not support the conclusion that the eNOS Asp298 allele contributes to the development of premature CAD.

Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992.

BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification.

Knowledge and awareness of risk factors for cardiovascular disease among Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992.

BACKGROUND: Cardiovascular disease is the leading cause of death and disability in older people, who account for an increasing proportion of Canada's population. Knowledge and awareness of risk factors is essential for changes in behaviour, yet little is known about these issues in older people. The Canadian Heart Health Surveys database provides a unique resource to examine knowledge and awareness of cardiovascular risk factors in older Canadians. METHODS: This descriptive cross-sectional study used data from the Canadian provinces' Heart Health Surveys, for the years 1986 to 1992. Sampling within each province consisted of stratified, 2-stage, replicated probability samples; 4976 people 55 to 74 years of age were included in the present analysis. Knowledge and awareness of cardiovascular risk factors was determined from the survey question "Can you tell me what are the major causes of heart disease or heart problems?" Blood pressure was measured during a home visit; anthropometric and blood measurements were obtained during a clinic visit. Cardiovascular health status was determined by self-reporting. RESULTS: Smoking and stress or worry were mentioned as major causes of heart disease by the greatest proportion of participants (41% and 44% respectively); hypertension was mentioned by only 16%. Men and women did not differ in their awareness of high blood cholesterol (cited by 23% of participants), smoking (41%), excess weight (30%) or lack of exercise (28%) as causes of heart disease. A greater proportion of women than men were aware of hypertension (19% v. 12%) and heredity (31% v. 17%) as major causes of heart disease. Awareness of risk factors was consistently lower in the older age group (65-74 v. 55-64 years). Among women, there was greater awareness of the respective risk factors as causes of heart disease among those who were smokers (60% v. 35% of nonsmokers), those who had a body mass index (BMI) of 25 or greater (38% v. 24% of those with a BMI less than 25) and those who were hypertensive (22% v. 17% of those without hypertension). Those who had experienced a heart attack had greater awareness of the major causes of heart disease than those who had not; this pattern was stronger among women than among men. Of those in whom elevated cholesterol level was identified during the course of the study, 62% of men and 67% of women were unaware of their cholesterol status. Of those in whom high blood pressure was diagnosed, 43% of men and 33% of women were unaware of their hypertensive status. INTERPRETATION: Awareness of the major causes of cardiovascular disease is low among older Canadians, especially among men and in those 65 to 74 years of age.

Relation of genetic polymorphisms of apolipoprotein E, angiotensin converting enzyme, apolipoprotein B-100, and glycoprotein IIIa and early-onset coronary heart disease.

OBJECTIVE: Apolipoprotein E (APOE) E4, apolipoprotein B-100 (APOB) Q3611 allele, the angiotensin converting enzyme (ACE) deletion (D) allele and glycoprotein IIIa (GP3A) P33 mutant allele are reported to predispose to early-onset coronary heart disease (CHD). These associations were not all confirmed in more recent studies. To determine the impact of these alleles on CHD, we examined the prevalence of these mutations in patients presenting with early-onset CHD and compared them to those manifesting CHD later in life. The delayed-onset was considered a sign of longevity and would serve as a comparative group to assess prevalence of the biochemical and genetic risk factors. METHODS: 300 patients with a history of myocardial infarction or angina pectoris and angiographically documented CHD were studied. Patients were divided into two groups: group 1 (G1 = 150 patients) presenting with these findings under the age of 50 years; while group 2 (G2 = 150 patients) were patients presenting for the first time over the age of 65 years. Prevalence of the alleles of APOE, APOB, ACE and GP3A was assessed by molecular analysis. An association of any of these genotypes with early onset CHD could lead to a higher prevalence in the younger age group. RESULTS AND CONCLUSIONS: None of the suspected alleles namely APOB Q3611 [G1: 10.7% vs. G2: 9.0%, p = 0.57], ACE D (G1: 52.0% vs. G2: 49.7%, p = 0.57), or the GP3A P33 (G1: 17.3% vs. G2: 15.7%; p = 0.58) showed any significant difference between the two groups. Subjects with APOE E4 were more frequent in the younger age group (G1: 18.3% vs. G2: 13.7%; p = 0.047), while APOE E2 was more frequent in G2 (G2: 10.0% vs. G1: 2.7%; p = 0.0002). Multivariate analysis showed an odds ratio of APOE E2 allele in G1 of 0.27 with a confidence interval of 0.10-0.73.

Risk scoring, fetal fibronectin, and bacterial vaginosis to predict preterm delivery.

OBJECTIVE: To determine the value of markers for predicting spontaneous preterm birth. METHODS: One hundred forty asymptomatic gravidas were recruited from 20-24 weeks' gestation. Risk score was assessed, vaginal swabs were analyzed for bacterial vaginosis, and cervical and vaginal swab were tested for fetal fibronectin FDC-6, X18A4, and CAF. Univariate analysis was used to determine potential predictors (and combinations of predictors) of outcome. Multiple logistic regression was done to identify independent predictors of spontaneous preterm birth. Sensitivity, specificity, positive and negative predictive values; and odds and likelihood ratios were calculated for significant predictors. RESULTS: Predictors significantly associated with the primary outcome were preterm birth-risk score and vaginal fetal fibronection FDC-6 (logistic regression odds ratio [OR] 16.9 [95% confidence interval (CI) 3.1, 92.8]) and 8.0 ([95% CI 1.6, 38.2], respectively). Bacterial vaginosis, fetal fibronectin X18A4, fibronectin CAF, and cervical fetal fibronectin FDC-6 were not associated with spontaneous preterm birth; however, the statistical power to assess these variables was limited. The combination of positive preterm birth-risk score and vaginal fetal fibronectin FDC-6 had a sensitivity of 44.4%, specificity of 97.7%, positive predictive value of 57.1%, negative predictive value of 96.2%, and a significant likelihood ratio for a positive test of 19.4 (95% CI 5.1, 73.8). CONCLUSION: The combination of preterm birth-risk score and vaginal fetal fibronectin FDC-6 predicted spontaneous preterm birth. Intervention trials are required to determine whether a combination of screening tests will reduce rates of spontaneous preterm birth.

Relation of a common mutation in methylenetetrahydrofolate reductase to plasma homocysteine and early onset coronary artery disease.

OBJECTIVE: In the presence of low serum folate, mutant 5,20-methylenetetrahydrofolate reductase (MTHFR + [A223V/C677T]) in the homozygous state (+/+), may predispose to higher plasma homocysteine (tHct) levels and coronary artery disease (CAD). To determine the impact of this relationship on predisposition to early-onset CAD, we examined the prevalence of the mutation and plasma tHct in patients with early-onset CAD and compared them to patients manifesting CAD later in life. METHODS: Three hundred patients with history of acute myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients) presenting with these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation was assessed by molecular analysis, and plasma tHct and folate were measured. An association of the +/+ genotype with early onset CAD could lead to its higher prevalence in the younger age group. RESULTS: There was no significant difference in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2: 11.3%). However, patients with the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01). CONCLUSION: The mutant MTHFR genotype was not found to be a determining factor in early-onset CAD. Higher tHct values were obtained in the older age group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTHFR genotype and low folate status yielding high tHct levels in those with the (+/+) genotype. As this relation was seen in both groups, although to a lesser extent in the older G2, it does not explain the underlying cause of early-onset CAD.

Relation of HFE gene mutations, high iron stores and early onset coronary artery disease.

OBJECTIVE: To determine the impact of mutations in the HFE gene (human leukocyte antigen H) on predisposition to coronary artery disease (CAD) in patients not diagnosed with hereditary hemochromatosis. BACKGROUND: Elevated iron stores can predispose to acute myocardial infarction. Two mutations (C282Y and H63D) in the novel major histocompatibility complex (MHC) class 1 gene HFE were found in most patients with hereditary hemochromatosis causing high iron stores. The effect of these mutations on predisposition to CAD has not been investigated previously. METHODS: Three hundred patients with a history of myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients were divided into two groups: group 1 (150 patients), manifesting early onset CAD and presenting with these findings under age 50 years; and group 2 (150 patients), presenting for the first time over age 65 years. Prevalence of the C282Y and H63D mutations was assessed by molecular analysis, and plasma ferritin was measured immunochemically. RESULTS: There was no difference in the prevalence of homozygous, heterozygous or compound heterozygous (C282Y/H63D) states between the groups. Males in group 1 had higher plasma ferritin than those in group 2 (234 +/- 174 micrograms/L versus 136 +/- 103 micrograms/L, P < 0.0001), but this was not significantly different in females (75 +/- 54 micrograms/L versus 92 +/- 73 micrograms/L, P = 0.26). Ferritin remained higher in group 1 than in group 2 males after exclusion of mutation carriers (195 +/- 121 micrograms/L versus 109 +/- 76 micrograms/L, respectively, P < 0.0001), but did not change in females. CONCLUSIONS: Higher iron stores were found in males with early onset CAD. This association was not related to the C282Y or H63D mutation in HFE. It is suggested that association of the MHC locus with delayed onset CAD is probably unrelated to HFE in these patients, and that HFE mutations are not a major risk factor in the development of high iron stores in early onset CAD.

Wheelchair-related accidents caused by tips and falls among noninstitutionalized users of manually propelled wheelchairs in Nova Scotia.

The purpose of this study was to document what proportion of noninstitutionalized users of manually propelled wheelchairs are affected by wheelchair-related accidents caused by tips and falls, determine the nature and severity of the resulting injuries, and, by comparison with an unaffected group, identify factors associated with the risk of such accidents. We administered a postal questionnaire to as many as possible of the estimated 2055 members of the target population in the province of Nova Scotia. Among the 577 appropriate respondents, 57.4% reported they had completely tipped over or fallen from their wheelchairs at least once, and 66.0% reported having partially tipped. Of the falls and tips that were reported, 46.3% were forward in direction, 29.5% backward and 24.2% sideways. Many of the accidents occurred outdoors or on ramps. A total of 292 injuries were reported by 272 (47.1%) respondents. Most of the injuries (84.3%) were minor (e.g., abrasions, contusions, lacerations and sprains). Of the 15.8% of injuries that were serious, the most common were fractures (10.6%) and concussions (2.7%). Factors that appear to be associated with an increased risk of accidents and injuries included younger age, male gender, paraplegia or spina bifida as the reason for wheelchair use, having had a wheelchair prescribed, some wheelchair features (lightweight, camber, adjustable rear-axle positions, a knapsack), daily use of a wheelchair, propelling the chair with both hands, use of the wheelchair for recreation, use of a sideways transfer (without a transfer board) and doing repairs themselves or having them done by the dealer. Factors associated with a decreased risk include multiple sclerosis, stroke or arthritis as the reason for wheelchair use, attendant propulsion and the use of a one-person assist for transfers. The results of this study, that wheelchair-related accidents caused by tips and falls are very common, that serious injuries are not unusual and that there is a pattern of risk factors, should be useful to wheelchair users, clinicians, manufacturers and regulatory bodies.