Sex-specific associations of body composition measures with cardiac function and structure after 8 years of follow-up.

We investigated the prospective associations of body composition with cardiac structure and function and explored effect modification by sex and whether inflammation was a mediator in these associations. Total body (BF), trunk (TF) and leg fat (LF), and total lean mass (LM) were measured at baseline by a whole body DXA scan. Inflammatory biomarkers and echocardiographic measures were determined both at baseline and follow-up in the Hoorn Study (n = 321). We performed linear regression analyses with body composition measures as determinant and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) or left atrial volume index (LAVI) at follow-up as outcome. Additionally, we performed mediation analysis using inflammation at follow-up as mediator. The study population was 67.7 ± 5.2 years and 50% were female. After adjustment, BF, TF and LF, and LM were associated with LVMI with regression coefficients of 2.9 (0.8; 5.1)g/m2.7, 2.3 (0.6; 4.0)g/m2.7, 2.0 (0.04; 4.0)g/m2.7 and - 2.9 (- 5.1; - 0.7)g/m2.7. Body composition measures were not associated with LVEF or LAVI. These associations were not modified by sex or mediated by inflammation. Body composition could play a role in the pathophysiology of LV hypertrophy. Future research should focus on sex differences in regional adiposity in relation with diastolic dysfunction.

Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study.

BACKGROUND: This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex. METHODS: Biomarkers and echocardiographic measures were measured at both baseline and follow-up in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders. RESULTS: Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %. CONCLUSION: Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers.

Cardiovascular risk factors and lifestyle behaviours in relation to longevity: a Mendelian randomization study.

BACKGROUND: The American Heart Association introduced the Life's Simple 7 initiative to improve cardiovascular health by modifying cardiovascular risk factors and lifestyle behaviours. It is unclear whether these risk factors are causally associated with longevity. OBJECTIVES: This study aimed to investigate causal associations of Life's Simple 7 modifiable risk factors, as well as sleep and education, with longevity using the two-sample Mendelian randomization design. METHODS: Instrumental variables for the modifiable risk factors were obtained from large-scale genome-wide association studies. Data on longevity beyond the 90th survival percentile were extracted from a genome-wide association meta-analysis with 11,262 cases and 25,483 controls whose age at death or last contact was ≤ the 60th survival percentile. RESULTS: Risk factors associated with a lower odds of longevity included the following: genetic liability to type 2 diabetes (OR 0.88; 95% CI: 0.84;0.92), genetically predicted systolic and diastolic blood pressure (per 1-mmHg increase: 0.96; 0.94;0.97 and 0.95; 0.93;0.97), body mass index (per 1-SD increase: 0.80; 0.74;0.86), low-density lipoprotein cholesterol (per 1-SD increase: 0.75; 0.65;0.86) and smoking initiation (0.75; 0.66;0.85). Genetically increased high-density lipoprotein cholesterol (per 1-SD increase: 1.23; 1.08;1.41) and educational level (per 1-SD increase: 1.64; 1.45;1.86) were associated with a higher odds of longevity. Fasting glucose and other lifestyle factors were not significantly associated with longevity. CONCLUSION: Most of the Life's Simple 7 modifiable risk factors are causally related to longevity. Prevention strategies should focus on modifying these risk factors and reducing education inequalities to improve cardiovascular health and longevity.

Characteristics associated with polypharmacy in people with type 2 diabetes: the Dutch Diabetes Pearl cohort.

AIM: To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes. METHODS: We included people with type 2 diabetes from the Diabetes Pearl cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5-9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0-4 medications). RESULTS: Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3-7) in primary care and 7 (IQR 5-10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose-lowering and lipid-modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non-cardiovascular and non-glucose-lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease. CONCLUSIONS: Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes.

The prevalence and incidence of vertebral fractures in end-stage renal disease and the role of parathyroid hormone.

The risk of vertebral fracture is unclear in end-stage renal disease. We report a high vertebral fracture prevalence and incidence in transplantation-eligible patients on dialysis, suggesting that these patients may benefit from radiographic screening for vertebral fractures. Parathyroid hormone had a U-shaped association with vertebral fracture risk. INTRODUCTION: Vertebral fractures are often overlooked, but even undiagnosed vertebral fractures negatively impact physical functioning, quality of life, and mortality. The risk of vertebral fractures in end-stage renal disease (ESRD) patients is unclear, and parathyroid hormone (PTH) might play a role in the development of vertebral fractures. We therefore determined vertebral fracture prevalence and incidence in ESRD patients and assessed associations of vertebral trabecular bone mineral density (BMD) and PTH with vertebral fracture. METHODS: In 146 transplantation-eligible patients on dialysis, we determined vertebral fractures on lateral chest radiographs, which image the thoracic and upper lumbar spine. We determined incident vertebral fractures in 70 patients with follow-up radiographs (23 received a kidney transplant) after median 1.8 years. Vertebral trabecular BMD was measured with computed tomography, and PTH measured with 2-site immunoassays, categorized in tertiles with the middle tertile as reference. We used Poisson regression to assess associations of vertebral trabecular BMD and PTH with vertebral fracture. RESULTS: Mean age of the study population was 52 ± 13 years, and 98 (67%) were male. Median dialysis duration was 26 (IQR 13-55) months. Vertebral fractures were present in 50/146 patients (34%) and incident vertebral fractures occurred in 20/70 patients (29%). Vertebral trabecular BMD was not associated with vertebral fracture prevalence (relative risk 0.97, 95% CI 0.89 to 1.04). For the lowest PTH tertile (< 11 pmol/L), the relative risk of vertebral fracture was greater although not significant (2.28, 95% CI 0.97 to 5.97) and was significantly greater for the highest PTH tertile (≥ 30 pmol/L; 2.82, 95% CI 1.22 to 7.27) after adjustment for potential confounders. CONCLUSIONS: The prevalence and incidence of vertebral fractures is high even in relatively young and healthy ESRD patients. Vertebral trabecular BMD is not associated with vertebral fracture, and the association of PTH with vertebral fracture risk appears U-shaped. Nevertheless, our study did not measure vertebral BMD using DXA and assessed vertebral fractures using lateral chest radiographs and not spine radiographs.

The Role of Vitamin K Status in Cardiovascular Health: Evidence from Observational and Clinical Studies.

PURPOSE OF REVIEW: Vitamin K is a fat-soluble vitamin required for the activation of several vitamin K-dependent proteins to confer functioning. A growing body of evidence supports that vitamin K has beneficial effects on bone and cardiovascular health. This review summarizes key evidence on vitamin K status as measured by circulating measures and cardiovascular outcomes. RECENT FINDINGS: Overall, observational studies indicate that low vitamin K status as measured by high dephosphorylated uncarboxylated matrix gla protein concentrations plays a potential role in cardiovascular disease development, particularly in high-risk and chronic kidney disease populations. Very few vitamin K intervention trials have been conducted with cardiovascular-related outcomes. A couple of intervention trials studied the effect of the combination of vitamin D + K supplementation, which might have synergistic effects compared to vitamin K supplementation alone. SUMMARY: Assessing vitamin K status in prospective studies and well-designed randomized trials would provide important insight whether vitamin K is causally related to vascular calcification and cardiovascular disease.

Associations of serum n-3 and n-6 polyunsaturated fatty acids with echocardiographic measures among older adults: the Hoorn Study.

BACKGROUND/OBJECTIVES: Lower circulating polyunsaturated fatty acids (PUFAs) may induce loss of heart function. We investigated whether lower concentrations of n-3 and n-6 PUFAs were associated with less favourable echocardiographic measures and higher heart rate in older Caucasians, cross-sectionally and after 7 years of follow-up. SUBJECTS/METHODS: We used data from the Hoorn Study, a population-based cohort. Cross-sectional data were available for 621 participants and longitudinal data for 336 participants. Mean age was 68.6±6.8 years at baseline. We performed linear regression analyses using n-3 and n-6 PUFAs quartiles-assayed by gas liquid chromatography-with left ventricular ejection fraction (LVEF), left ventricular mass index, left atrial volume index and heart rate. RESULTS: In multivariable analyses (regression coefficient (95% confidence interval)), the lowest eicosapentaenoic acid and docosahexaenoic acid quartiles compared with the highest quartiles were cross-sectionally associated with lower LVEF. Lower eicosapentaenoic acid and docosahexaenoic acid concentrations were associated with higher heart rate: 3.7 b.p.m. (1.5, 6.0; P for trend <0.001) and 3.4 b.p.m. (1.2, 5.6; P for trend 0.001), respectively. Multivariate longitudinal analyses showed a significant trend across quartiles for alpha-linolenic acid in relation to LVEF. The lowest linoleic acid quartile was significantly associated with a decreased LVEF of -4.0% compared with the highest quartile. CONCLUSIONS: This study found no strong evidence of longitudinal associations of eicosapentaenoic acid and docosahexaenoic acid with echocardiographic measures, however, lower concentrations of alpha-linolenic acid and linoleic acid were associated with decreased LVEF. These results provide evidence for a potential protective role of alpha-linolenic acid and linoleic acid in relation to systolic function.

Serum vitamin D and parathyroid hormone in relation to cardiac structure and function: the ICELAND-MI substudy of AGES-Reykjavik.

CONTEXT: Emerging evidence suggests that vitamin D and PTH may play a role in the development of cardiac diseases. OBJECTIVE: We investigated whether 25-hydroxyvitamin D (25OHD) and PTH concentrations are cross-sectionally associated with cardiac structure and function using magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: ICELAND-MI is a substudy of the Age, Gene/Environment Susceptibility-Reykjavik Study, an older-aged community-dwelling cohort with oversampling of participants with diabetes (29%) and measurements between 2004 and 2007. Serum 25OHD concentrations were measured using an immunoassay (n = 992). Intact PTH concentrations were measured using a 2-site immunoassay (n = 203). We included 969 participants for this cross-sectional analysis (mean age 76 ± 5.3 years, 51% female). Mean 25OHD was 54.2 ± 25.5 nmol/L and the median PTH was 4.5 pmol/L (range 1.5-18). MAIN OUTCOMES: MRI to measure cardiac structure and function was the main outcome. RESULTS: The lowest 25OHD category (<25 nmol/L) compared with the highest category (≥75 nmol/L) was associated with a smaller left and right atrial area in unadjusted analyses; however, the associations became nonsignificant after adjustment for covariates. The highest PTH quartile compared with the lowest quartile was significantly associated with a 7.3 g (95% confidence interval 0.8, 13.8) greater left ventricular (LV) mass and a 5.1% (-9.1, -1.1) lower LV ejection fraction compared with the lowest PTH quartile in the fully adjusted model. CONCLUSIONS: Serum 25OHD concentrations were not associated with MRI measures in an older white population. Higher PTH concentrations were associated with greater LV mass and lower systolic function and may point to a potential role for PTH as a determinant of cardiac remodeling.

Serum parathyroid hormone in relation to all-cause and cardiovascular mortality: the Hoorn study.

CONTEXT: Higher PTH concentrations have been associated with fatal cardiovascular diseases (CVDs), but data in the general population are scarce. OBJECTIVE: We investigated whether higher PTH concentrations are prospectively associated with all-cause and CVD mortality. DESIGN, SETTING, PARTICIPANTS: This study used data from the Hoorn Study, a prospective population-based cohort with baseline measurements between 2000 and 2001. We included 633 participants, mean age 70.1 ± 6.6 years, 51% female. Serum intact PTH was measured using a 2-site immunoassay. MAIN OUTCOME MEASURES: Outcomes were all-cause and CVD mortality based on clinical files and coded according to the International Classification of Diseases, ninth revision. We used Kaplan-Meier plots to estimate survival curves and Cox regression to estimate hazard ratios (HRs) using season-specific PTH quartiles. RESULTS: During a median follow-up of 7.8 years, 112 participants died, of which 26 deaths (23%) were cardiovascular. Survival curves by PTH quartiles differed for all-cause mortality (log-rank P = .054) and CVD mortality (log-rank P = .022). In a multivariate model, the highest PTH quartile was associated with all-cause mortality; HR = 1.98 (1.08, 3.64). Kidney function slightly attenuated the PTH risk association, but risk persisted; HR = 1.93 (1.04, 3.58). The results for CVD mortality showed a similar pattern, although the association was significant only in a threshold model (quartile 4 vs quartile 1-3); HR = 2.56 (1.11, 5.94). CONCLUSIONS: Among a general older population, higher PTH concentrations were associated with higher all-cause mortality risk, mostly explained by fatal CVD events. We suggest to evaluate whether individuals with high PTH concentrations benefit from therapeutic approaches targeted to decrease PTH concentrations.

Determinants of adherence to heart failure medication: a systematic literature review.

A systematic literature review was conducted to summarize the existing evidence on presumed determinants of heart failure (HF) medication adherence. The aim was to assess the evidence and provide directions for future medication adherence interventions for HF patients. Based on a search in relevant databases and a quality assessment, eleven articles were included in the review. A best evidence synthesis was used to combine the results of presumed determinants that were found more than once in the literature. Results were classified according the World Health Organization's (WHO) multidimensional adherence model. Results demonstrated a relationship between having been institutionalized in the past (including hospitalizations and nursing home visits) and higher adherence levels. This finding is related to the healthcare system dimension of the WHO model. The presumed determinants related to the other dimensions, such as social and economic factors, condition-related, therapy-related, and patient-related factors of the multidimensional adherence model all had inconsistent evidence. However, there was also an indication that patients' educational level and the number of healthcare professionals they have visited are not related to higher adherence levels. Based on the current review, HF patients who have been institutionalized in the past are more adherent to HF medication. Many other presumed determinants were investigated, but displayed inconsistent evidence. Due to the lack of evidence, it was not possible to make recommendations for future interventions.

Vitamin D in relation to myocardial structure and function after eight years of follow-up: the Hoorn study.

BACKGROUND AND AIMS: To investigate associations between baseline serum 25-hydroxyvitamin D [25(OH)D] levels and myocardial structure and function after 8 years of follow-up in older Dutch subjects. METHODS: We included 256 subjects of the Hoorn Study, a population-based cohort. They underwent a standardized 2-dimensional echocardiogram at baseline between 2000 and 2001, and again between 2007 and 2009. We studied the association of 25(OH)D quartiles with echocardiographic measures of the left ventricular mass index (LVMI), left ventricular systolic function and markers of diastolic function using linear regression analyses. RESULTS: At baseline, subjects had a mean age of 67.4 ± 5.2 years and 41.4% had prior cardiovascular disease (CVD). Low serum 25(OH)D levels were only associated with higher LVMI at 8-year follow-up in subjects without prior CVD and in subjects with low kidney function (median estimated glomerular filtration rate ≤77.5 ml/min/1.73m(2)). The associations attenuated after adjustments for parathyroid hormone (PTH), which was associated with higher LVMI (g/m(2.7)) in subjects with low kidney function (regression coefficient highest quartile 6.3, 95% CI: 0.2, 12.5). CONCLUSION: This study showed no strong associations of 25(OH)D with myocardial structure and function. However, PTH - a possible modifiable mediator in the relation between 25(OH)D and myocardial structure - was positively associated with LVMI in subjects with low kidney function.

Determinants of heart failure self-care: a systematic literature review.

Self-care is an important aspect of heart failure (HF) management. Information on the determinants of self-care is necessary for the development of self-care promotion interventions. HF self-care includes self-care management, self-care maintenance, sodium, fluid and alcohol intake restriction, physical activity, smoking cessation, monitoring signs and symptoms and keeping follow-up appointments. To assess the evidence regarding presumed determinants of HF self-care and make recommendations for interventions to promote self-care behavior among HF patients, a systematic literature review was conducted. Based on inclusion and exclusion criteria and a quality assessment, twenty-six articles were included. A best evidence synthesis was used. Results showed that the length of time since patients' diagnosis with HF is positively related to their performance of self-care maintenance. Moreover, it was found that HF patients' perceived benefits and barriers are related to their restriction of sodium intake, and that patients with type-D personality are less likely to consult medical professionals. There was also evidence for a few non-significant relationships. All other evidence was inconsistent, mainly due to insufficient evidence. Interventions that aim to increase the performance of self-care maintenance can teach newly diagnosed patients the skills that are usually attained with experience acquired as a result of living with HF for a longer time. Perceived benefits and barriers of restricting sodium intake could be targeted in interventions for sodium intake reduction among HF patients. Finally, interventions for the promotion of adequate consulting of medical professionals can specifically target HF patients with a type-D personality.

Evidence for Alfvén waves in solar x-ray jets.

Coronal magnetic fields are dynamic, and field lines may misalign, reassemble, and release energy by means of magnetic reconnection. Giant releases may generate solar flares and coronal mass ejections and, on a smaller scale, produce x-ray jets. Hinode observations of polar coronal holes reveal that x-ray jets have two distinct velocities: one near the Alfvén speed ( approximately 800 kilometers per second) and another near the sound speed (200 kilometers per second). Many more jets were seen than have been reported previously; we detected an average of 10 events per hour up to these speeds, whereas previous observations documented only a handful per day with lower average speeds of 200 kilometers per second. The x-ray jets are about 2 x 10(3) to 2 x 10(4) kilometers wide and 1 x 10(5) kilometers long and last from 100 to 2500 seconds. The large number of events, coupled with the high velocities of the apparent outflows, indicates that the jets may contribute to the high-speed solar wind.

Training and experience of examiners.

Variation in the accuracy of examiner judgements is a source of measurement error in performance-based tests. In previous studies using doctor subjects, examiner training yielded marginal or no improvement in the accuracy of examiner judgments. This study reports an experiment on accuracy of scoring in which provision of training and background of examiners are systematically varied. Experienced teaching staff, medical students and lay subjects were randomly assigned to either training or no-training groups. Using detailed behavioural check-lists, they subsequently scored videotaped performance on two clinical cases, and accuracy of their judgments was appraised. Results indicated that the need for and effectiveness of training varied across groups: it was least needed and least effective for the teaching staff group, more needed and effective for medical students, and most needed and effective for the lay group. The accuracy of the lay group after training approached the accuracy of untrained teaching staff. Trained medical students were as accurate as trained teaching staff. For teaching staff and medical students training also influenced the nature of errors made by reducing the number of errors of commission. It was concluded that training varies in effectiveness as a function of medical experience and that trained lay persons can be utilized as examiners in performance-based tests.