Telehealth Cognitive Behavior Therapy to Reduce Anxiety in People Living with Cognitive Impairment: A Randomized Feasibility Pilot Study.

OBJECTIVES: To evaluate the feasibility of telehealth-based cognitive behavior therapy for people living with cognitive impairment experiencing anxiety (Tele-CBT), and to assess whether this leads to improvements in anxiety, depression, and quality of life post-intervention. METHODS: This was a single-blind randomized feasibility pilot trial of the Tele-CBT versus usual care. People living with mild cognitive impairment or dementia experiencing anxiety were recruited and randomized to receive Tele-CBT (n = 5) or continue usual care (n = 5). Feasibility data comprised recruitment uptake and retention, adherence, and ease of use. Outcomes of anxiety (primary outcome - Rating Anxiety in Dementia; RAID), depression, stress, and quality of life were measured pre- and post-intervention. RESULTS: Intervention feasibility was demonstrated through minimal attrition, acceptability, and ease of use via videoconferencing. Both groups showed a decrease of anxiety symptoms (RAID) from baseline to post-assessment. CONCLUSIONS: The Tele-CBT program was acceptable to use via videoconferencing. Reduced anxiety symptoms were observed in both groups at post-. An RCT with a larger sample is required to determine the efficacy and implementation of the intervention. CLINICAL IMPLICATIONS: This study indicates the feasibility of videoconference CBT to address anxiety experienced by people living with cognitive impairment with minimal assistance from support persons.

Feasibility and Acceptability of a Videoconferencing CBT Intervention for Anxiety in People with Parkinson's Disease.

OBJECTIVES: In people with Parkinson's disease (PwPD), non-motor symptoms such as anxiety are common and have negative impacts on their quality of life. There are currently few interventions that address anxiety in PwPD, and access to diagnosis and treatment is often limited for those living in rural areas. The aim of this study was to evaluate the feasibility and acceptability of a telehealth videoconferencing CBT intervention for anxiety in PwPD. METHODS: A pre- and post-test feasibility study (N = 10) was conducted and evaluated utilizing the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance). RESULTS: Lack of access to the internet and videoconferencing technology were identified as barriers to participation. Physical health issues also impacted recruitment and retention. Non-completers were significantly older and less likely to have a carer involved in the intervention. Clinician adoption of the intervention was low while participant acceptability of videoconferencing technology varied and required carer support. CONCLUSIONS: Providing access to technology and support to overcome technological issues, as well as telehealth training for clinicians, are recommended in future studies to improve recruitment, retention, and implementation. CLINICAL IMPLICATIONS: Identification of barriers and facilitators provides future studies with the knowledge to tailorize their program to better suit PwPD.

Phenomenology of anxiety in people living with mild to moderate dementia: A conceptual meta-ethnographic review.

OBJECTIVES: This conceptual review aims to integrate findings from published qualitative studies focusing on individual experiences of people living with dementia to generate a better understanding and conceptualisation of anxiety in dementia, including its subclinical manifestations. The review aims to inform the clinical practice to facilitate the development of targeted psychological interventions and provision of holistic support to people living with dementia. DESIGN: The review was conducted according to the guide for reporting meta-ethnographic qualitative syntheses eMERGe and the PRISMA guidelines. RESULTS: The search yielded a total of 2947 studies, out of which 13 were included in the final qualitative synthesis. The interpretive synthesis identified common experiences of people living with mild to moderate dementia, characterised by clusters of themes around worry, emotional experiences, and behavioural reactions in response to the diagnosis of dementia and its symptoms. These represent the components of a conceptual framework of anxiety in mild to moderate dementia, where anxiety is triggered by negative appraisals of living with an irreversible neurodegenerative disease. Stemming from these appraisals of dementia progression and its impact on the person's overall future, the content of worrisome thoughts and concerns include the loss of self and identity, losing independence and the ability to perform previous activities, concerns about being a burden to loved ones, and worry about the impact on interpersonal relationships. CONCLUSION: This conceptualisation of anxiety in dementia, including its subclinical manifestations facilitates the development of psychological interventions and provision of holistic support to people living with dementia.

A Copper Cage-Complex as Mimic of the pMMO CuC Site.

The active site of particulate methane monooxygenase (pMMO) and its mechanism of action are not known. Recently, the CuC site emerged as a potential active site, but to date it lacks any study on biomimetic resemblance of the coordination environment provided by the enzyme. Here, the synthesis of a cage ligand providing such an environment is reported. Copper is incorporated, and coordination occurs by the two imidazole and one carboxylate group offered by the ligand. Depending on the oxidation state, it can adopt different coordination modes, as evidenced by the solid-state structures and computational investigation. The copper(I) state readily reacts with dioxygen and thereby undergoes CH activation. Moreover, the catalytic aerobic oxidation of hydroquinones as ubiquinol mimics is shown. Clean one-electron oxidation occurs under mild conditions and EPR analysis of the copper(II) state in the presence of water reveals striking similarities to the data obtained from pMMO.

A Systematic Review of Psychotherapy Approaches for Anxiety in Parkinson's Disease.

OBJECTIVES: Anxiety is common in Parkinson's disease (PD), negatively impacting daily functioning and quality of life in PD patients and their families. This systematic review evaluates the effectiveness of different psychotherapeutic approaches for reducing anxiety in PD and provides recommendations for clinical practise. METHODS: Following PRISMA guidelines, 36 studies were included and risk of bias was evaluated. RESULTS: We identified cognitive behavioral therapy (CBT), mindfulness-based therapies, acceptance and commitment therapy, and psychodrama psychotherapies. There is good evidence-base for anxiety reduction using CBT approaches, but with mixed results for mindfulness-based therapies. Other therapeutic approaches were under researched. Most randomized control trials examined anxiety as a secondary measure. There was a paucity of interventions for anxiety subtypes. Secondarily, studies revealed the consistent exclusion of PD patients with cognitive concerns, an importance of care partner involvement, and a growing interest in remote delivery of psychotherapy interventions. CONCLUSIONS: Person-centered anxiety interventions tailored for PD patients, including those with cognitive concerns, and trials exploring modalities other than CBT, warrant future investigations. CLINICAL IMPLICATIONS: Practitioners should consider PD-specific anxiety symptoms and cognitive concerns when treating anxiety. Key distinctions between therapeutic modalities, therapy settings and delivery methods should guide treatment planning.

Caring for a loved one with Parkinson's disease: the role of coping styles and relationship quality.

OBJECTIVE: Informal carers play an essential role in the care of individuals with Parkinson's disease (PD). This role, however, is often fraught with difficulties, including emotional, physical, and financial. Coping styles and relationship quality have been hypothesized to influence the impact of stressors. The aim of this study is to examine the relationship between carers' coping style, relationship quality, and carer burden. DESIGN: Cross-sectional. PARTICIPANTS: Thirty-nine PD patient carer dyads were included in the study. MEASUREMENTS: Participants completed self-rated questionnaires including the Dyadic Adjustment Scale, Zarit Burden Interview, and Brief Coping Orientation to Problems Experienced Inventory. RESULTS: Correlational analyses found significant and positive correlation between carer burden and all three coping styles (problem-focused, emotion-focused, and dysfunctional). There was also a moderate association between carers' perceived relationship quality and satisfaction and carer burden. Regression analyses found that carer's gender, severity of PD, relationship quality, emotion-focused, and dysfunctional coping styles did not predict carer burden. Conversely, problem-focused coping style predicted carer burden. CONCLUSION: The results highlight that there is no perfect way to react and care for a loved one and serves as important information for practitioners who design and implement interventions.

Designing Virtual Reality Assisted Psychotherapy for Anxiety in Older Adults Living with Parkinson's Disease: Integrating Literature for Scoping.

Objective: This review integrates literature to discuss the potential use of virtual reality (VR) in treatment of anxiety in Parkinson's disease (PD) and inform next steps.Methods: A systematic search was performed to identify studies of VR use in PD, using four databases. Data were reported in accordance to the Preferred Reporting Items for Systematic reviews and Meta-Analyzes extension for Scoping Reviews (PRISMA-ScR).Results: Thirty-two studies met the inclusion criteria with four VR studies from the same study group directly assessing the effects of anxiety on motor symptoms in PD. Primary studies implementing a VR protocol in PD identified focus areas of understanding and alleviating freezing of gait (FOG), balance training, and cognitive and motor rehabilitation, and informed design considerations.Conclusion: VR in PD studies suggested established feasibility. With appropriate design considerations, a VR based protocol could improve anxiety outcomes in PD.Clinical implications: VR in PD provides control of a patient's field of view, which can be exploited to induce specific responses, provide visual feedback, analysis of patient actions, and introduce safe challenges in the context of training. VR assisted Cognitive Behavioral Therapy (CBT) tailored to suit subtypes of anxiety disorders in PD have the potential to improve the efficacy and effectiveness of psychotherapy in PD.

Anxiety disorders are associated with verbal memory impairment in patients with Parkinson's disease without dementia.

INTRODUCTION: Preliminary evidence has demonstrated a link between anxiety and memory impairment in Parkinson's disease (PD). This study further investigated this association using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for anxiety disorders and a standardized cognitive test battery. METHODS: A convenience sample of 89 PD patients without dementia was recruited from neurology outpatient clinics. A cross-sectional design was applied. Participants completed two semi-structured interviews. The first interview diagnosed DSM-5 anxiety disorders, unspecified anxiety disorder, and no anxiety. The second interview applied a neurocognitive test battery comprising two tests for each domain. Logistic regression models compared cognitive characteristics associated with anxiety disorders to no anxiety. RESULTS: Clinically significant anxiety was associated with immediate verbal memory impairment compared to the no anxiety group (OR, 95% CI 0.52, 0.30-0.89; p = 0.018), controlling for sex and age. The anxiety disorders group demonstrated immediate (OR, 95% CI 0.46, 0.26-0.83; p = 0.010) and delayed (OR, 95% CI 0.63, 0.40-0.99; p = 0.047) verbal memory impairments compared to those without anxiety, controlling for sex and age. This association remained for immediate (OR, 95% CI 0.43, 0.22-0.84; p = 0.013), but not delayed verbal memory impairment (OR, 95% CI 0.65, 0.39-1.06; p = 0.081) when additionally controlling for disease severity, education and levodopa dose. CONCLUSION: These findings present first evidence that anxiety disorders are associated with verbal memory impairment in PD and have implications for the management and treatment of anxiety in PD.

Interprofessional, student-led community health clinic: expanding service provision and clinical education capacity.

Student-led interprofessional health clinics offer valuable opportunities for student learning and meeting the health care needs of the community. This case study describes the operation of a new interprofessional student-led community health service over its initial 13-month period of operation. This case study also presents an overview of the service provision, student placement opportunities and focuses on the challenges associated with the service and the impact on future planning.

Circulating fatty acids in relation to alcohol consumption: Cross-sectional results from a cohort of 60-year-old men and women.

BACKGROUND & AIMS: Alcohol consumption is considered to affect circulating fatty acids (FAs) but knowledge about specific associations is limited. We aimed to assess the relation between alcohol consumption and serum FAs in 60-year-old Swedish men and women. METHODS: In a random sample of 1917 men and 2058 women residing in Stockholm county, cross-sectional associations between different categories of alcohol consumption and FAs were assessed using linear regression; ß1 coefficients with 95% confidence interval (CI) were calculated. Self-reported alcohol consumption was categorized as none, low (≤9.9 g/day) (reference), moderate (10-29.9 g/day) and high (≥30 g/day). Moderate alcohol consumption was further subdivided into consumption of beer, wine, liquor and their combinations. Thirteen serum cholesterol ester FAs were measured by gas chromatography and individual FAs were expressed as percentage of total FAs. RESULTS: Increasing alcohol consumption was associated to linear increase of saturated myristic acid, monounsaturated FAs and n-6 polyunsaturated (PUFA) arachidonic acid, whereas linear decrease was noted for saturated pentadecanoic acid and for n-6 PUFA linoleic acid. With non-linear associations, increasing alcohol consumption also associated to decreased saturated stearic acid, n-6 PUFA dihomo-gamma-linolenic acid, and n-3 PUFA docosahexaenoic acid and increased saturated palmitic acid, n-6 PUFA gamma-linolenic acid and n-3 PUFA eicosapentaenoic acid. Among types of beverages, wine consumption was associated with n-6 PUFA arachidonic acid (ß1 0.59; 95% CI: 0.30;0.88) and the n-3 PUFAs eicosapentaenoic acid (ß1 0.54; 95% CI: 0.30;0.78), and docosahexaenoic acid (ß1 0.06; 95% CI: 0.00;0.12). CONCLUSIONS: These findings may give important basis for further investigations to better understand biological mechanisms behind the dose-dependent associations between alcohol consumption and health outcomes observed in many previous studies.

Wisdom across the ages and its modern day relevance.

Wisdom is derived (in modern language terms) from the Old English words wis ("of a certainty, for certain"; "Wisdom," 2015) and dóm ("statute, judgment, jurisdiction"; "Wisdom," 2015); wisdom is, at its broadest, defined as the "Capacity of judging rightly in matters relating to life and conduct; soundness of judgement in the choice of means and ends; sometimes less strictly, sound sense, esp. in practical affairs" ("Wisdom," 2015). As a concept, wisdom has been acknowledged within our history since the time of the Sumerians (and estimated to have originated in around 2,500 BCE). However, in modern times, the relevance of the traditional wise person is less clear. Nonetheless, wisdom research has been on the rise since it emerged as a focus of researchers in the 1970's, and a part of that research focus has been to explore the significance of wisdom and its relevance in the current day (particularly with regards to how it is measured across cultures).

Cognitive Behavior Therapy for Anxiety in Parkinson's Disease: Outcomes for Patients and Caregivers.

OBJECTIVE: Anxiety negatively impacts the quality of life of Parkinson's disease (PD) patients and caregivers. Despite high prevalence, there is a paucity of trials investigating effective treatments for anxiety in PD. This uncontrolled study investigated the use of a manualized and tailored Cognitive Behavior Therapy (CBT) for anxiety in PD. METHODS: Participants completed 6 weekly CBT sessions. Pre-, post- and follow-up (3 and 6 months) assessments were made. Change in outcomes were analysed using t-tests and Reliability Change Index. Of 17 PD patients who agreed to CBT, 12 completed the intervention. RESULTS: This study showed a significant reduction in Hamilton Anxiety Rating Scale scores in PD immediately post CBT (t(11) = 3.59, p < .01), maintained at 3-month (t(8) = 2.83, p = .02) and 6-month (t(7) = 2.07, p = .04) follow-up. A reduction in caregiver burden (t(11) = 2.68, p = .03) was observed post intervention. Improvements in motor disability (t(11) = 2.41, p = .04) and cognitive scores (t(11) = -2.92, p = .01) were also observed post intervention and at follow-up. CONCLUSIONS: Tailored CBT can be used to treat anxiety in PD. CLINICAL IMPLICATIONS: This study provides preliminary evidence suggesting that tailored CBT reduces anxiety in PD with persisting benefits, and lowers caregiver burden.

Cross-sectional relationships between dietary fat intake and serum cholesterol fatty acids in a Swedish cohort of 60-year-old men and women.

BACKGROUND: The present study aimed to describe the relationship between self-reported dietary intake and serum cholesterol fatty acids (FAs) in a Swedish population of 60-year-old men and women. METHODS: Cross-sectional data collected in 1997-1998 from 4232 individuals residing in Stockholm County were used. Five diet scores were created to reflect the intake of saturated fats in general, as well as fats from dairy, fish, processed meat and vegetable oils and margarines. Gas chromatography was used to assess 13 FAs in serum cholesterol esters. The association between each diet score and specific FAs was assessed by percentile differences (PD) with 95% confidence intervals (CI) at the 10th, 25th, 50th, 75th and 90th percentile of each FA across levels of diet scores using quantile regression. RESULTS: Fish intake was associated with high proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). For each point increase in fish score, the 50th PD in EPA and DHA was 32.78% (95% CI = 29.22% to 36.35%) and 10.63% (95% CI = 9.52% to 11.74%), respectively. Vegetable fat intake was associated with a high proportion of linoleic acid and total polyunsaturated fatty acids (PUFA) and a low proportion of total saturated fatty acids (SFA). The intake of saturated fats in general and dairy fat was slightly associated with specific SFA, although the intake of fat from meat was not. CONCLUSIONS: In the present study population, using a rather simple dietary assessment method, the intake of fish and vegetable fats was clearly associated with serum PUFA, whereas foods rich in saturated fats in general showed a weak relationship with serum SFA. Our results may contribute to increased knowledge about underlying biology in diet-cardiovascular disease associations.

Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

Financial capacity in older adults: a growing concern for clinicians.

Older people with cognitive impairment and/or dementia may be particularly vulnerable to diminished financial decision-making capacity. Financial capacity refers to the ability to satisfactorily manage one's financial affairs in a manner consistent with personal self-interest and values. Impairment of financial capacity makes the older individual vulnerable to financial exploitation, may negatively affect their family's financial situation and places strain on relationships within the family. Clinicians are often on the front line of responding to queries regarding decision-making capacity, and clinical evaluation options are often not well understood. Assessment of financial capacity should include formal objective assessment in addition to a clinical interview and gathering contextual data. Development of a flexible, empirically supported and clinically relevant assessment approach that spans all dimensions of financial capacity yet is simple enough to be used by non-specialist clinicians is needed.

Prediction of cardiovascular disease by abdominal obesity measures is dependent on body weight and sex--results from two community based cohort studies.

AIM: To study waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), and waist-hip-height ratio (WHHR) as predictors of CVD, in men and women stratified by BMI (cut-off ≥25). METHODS AND RESULTS: A cohort of n = 3741 (53% women) 60-year old individuals without CVD was followed for 11-years (375 CVD cases). To replicate the results, we also assessed another large independent cohort; The Malmö Diet and Cancer study - cardiovascular cohort (MDCC, (n = 5180, 60% women, 602 CVD cases during 16-years). After adjustment for established risk factors in normal-weight women, the hazard ratio (HR) per one standard deviation (SD) were; WHR; 1.91 (95% confidence interval (CI) 1.35-2.70), WC; 1.81 (95% CI 1.02-3.20), SAD; 1.25 (95% CI 0.74-2.11), and WHHR; 1.97 (95% CI 1.40-2.78). In men the association with WHR, WHHR and WC were not significant, whereas SAD was the only measure that significantly predicted CVD in men (HR 1.19 (95% CI 1.04-1.35). After adjustments for established risk factors in overweight/obese women, none of the measures were significantly associated with CVD risk. In men, however, all measures were significant predictors; WHR; 1.24 (955 CI 1.04-1.47), WC 1.19 (95% CI 1.00-1.42), SAD 1.21 (95% CI 1.00-1.46), and WHHR; 1.23 (95% CI 1.05-1.44). Only the findings in men with BMI ≥ 25 were verified in MDCC. CONCLUSION: In normal weight individuals, WHHR and WHR were the best predictors in women, whereas SAD was the only independent predictor in men. Among overweight/obese individuals all measures failed to predict CVD in women, whereas WHHR was the strongest predictor after adjustments for CVD risk factors in men.

Reasons for non-participation in population-based abdominal aortic aneurysm screening.

BACKGROUND: A population-based screening programme for abdominal aortic aneurysm (AAA) started in 2010 in Stockholm County, Sweden. This present study used individual data from Sweden's extensive healthcare registries to identify the reasons for non-participation in the AAA screening programme. METHODS: All 65-year-old men in Stockholm are invited to screening for AAA; this study included all men invited from July 2010 to July 2012. Participants and non-participants were compared for socioeconomic factors, travel distance to the examination centre and healthcare use. The influence of these factors on participation was analysed using univariable and multivariable logistic regression models. RESULTS: The participation rate for AAA screening was 77·6 per cent (18 876 of 24 319 men invited). The prevalence of AAA (aortic diameter more than 2·9 cm) among participants was 1·4 per cent. The most important reasons for non-participation in the multivariable regression analyses were: recent immigration (within 5 years) (odds ratio (OR) 3·25, 95 per cent confidence interval 1·94 to 5·47), low income (OR 2·76, 2·46 to 3·10), marital status single or divorced (OR 2·23, 2·08 to 2·39), low level of education (OR 1·28, 1·16 to 1·40) and long travel distance (OR 1·23, 1·10 to 1·37). Non-participants had a higher incidence of stroke (4·5 versus 2·8 per cent; P < 0·001) and chronic pulmonary disease (2·9 versus 1·3 per cent; P < 0·001). Daily smoking was more common in residential areas where the participation rate for AAA screening was low. CONCLUSION: Efforts to improve participation in AAA screening should target the groups with low income, a low level of education and immigrants. The higher morbidity in the non-participant group, together with a higher rate of smoking, make it probable that this group also has a high risk of AAA.

Promoting the use of enduring powers of attorney in older adults: a literature review.

This review aims to identify factors that facilitate the establishment of enduring powers of attorney (EPOAs), and those that create a barrier to their establishment. The primary aim was to provide guidance about how to encourage future planning while people are cognitively able to make such important decisions. A detailed search of the literature was conducted to identify research looking at the motivating factors behind putting future-planning strategies in place. The literature highlighted a number of broad areas motivating the establishment of EPOAs, including: demographic factors; intrapersonal and personality factors; health and psychological factors; cognitive factors; and socio-emotional factors. While a number of factors play a role in determining whether or not a person establishes an EPOA, the factor most malleable to change is the awareness and knowledge of older adults and their families regarding the utility of EPOAs.

Predictors of financial capacity performance in older adults using the Financial Competence Assessment Inventory.

BACKGROUND: Declines in financial capacity in later life may arise from both neurocognitive and/or psychiatric disorders. The influence of socio-demographic, cognitive, health, and psychiatric variables on financial capacity performance was explored. METHODS: Seventy-six healthy community-dwelling adults and 25 older patients referred for assessment of financial capacity were assessed on pertinent cognitive, psychiatric, and financial capacity measures, including Addenbrooke's Cognitive Examination - Revised (ACE-R), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Geriatric Depression Scale (GDS), Geriatric Anxiety Inventory (GAI), selected Neuropsychiatric Inventory (NPI) items, Financial Competence Assessment Inventory (FCAI), and Social Vulnerability Scale (SVS). RESULTS: The internal consistency of the debt management subscale of the FCAI was relatively poor in our sample. Financial capacity performance differed between controls and patients. In our sample, performance on the FCAI was predicted by Mini-Mental State Examination, IQCODE, and GAI, but not by ACE-R, GDS, NPI items, or SVS (adjusted R(2) = 0.7059). CONCLUSIONS: Anxiety but not depression predicted financial capacity performance, possibly reflecting relatively low variance of depressive symptoms in this sample. Current cognitive decline as measured by the informant-rated IQCODE was more highly correlated to financial capacity than either educational attainment or ACE-R scores. Lack of significance of ACE-R data may reflect the instrument's decreased sensitivity to domains relevant to financial capacity, compared with more detailed neuropsychological assessment tools. The FCAI displayed fairly robust psychometric properties apart from the debt management subscale.

The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.

OBJECTIVE: An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism. DESIGN AND SETTING: Data from two case-control studies of first-time myocardial infarction (MI), Stockholm Heart Epidemiology Programme (SHEEP), and for MI and unstable angina, INTERGENE, were analysed in parallel. PATIENTS: THcy was determined in a total of 1150 cases and 1753 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The outcome comprised first-time MI and unstable angina, subsumed as CHD. Logistic regression was used to investigate the association between tHcy and CHD, and its modification by genotype. RESULTS: High tHcy was confirmed to be a risk factor for CHD in both studies. In SHEEP, the association between tHcy and MI was observed in MTHFR 677 C-homozygotes (OR=1.4, 95% CI 1.2 to 1.6, for a difference by 1 SD of log tHcy) and in heterozygotes (OR=1.3, 95% CI 1.1 to 1.6) but not in T-homozygotes, independent of smoking, physical activity and obesity. An effect modification of similar magnitude was observed but not statistically significant in the smaller INTERGENE study, and confirmed in a meta-analysis of both studies. CONCLUSIONS: Two Swedish case-control studies showed that the association between elevated tHcy and CHD was confined to carriers of the MTHFR 677 C-allele, which could have implications for the efficiency of tHcy-lowering treatment.