SD Increase Research Articles

Nontargeted Metabolomics Revealed Novel Association Between Serum Metabolites and Incident Acute Coronary Syndrome: A Mendelian Randomization Study.

Background This study was performed to identify metabolites associated with incident acute coronary syndrome (ACS) and explore causality of the associations. Methods and Results We performed nontargeted metabolomics in a nested case-control study in the Dongfeng-Tongji cohort, including 500 incident ACS cases and 500 age- and sex-matched controls. Three metabolites, including a novel one (aspartylphenylalanine), and 1,5-anhydro-d-glucitol (1,5-AG) and tetracosanoic acid, were identified as associated with ACS risk, among which aspartylphenylalanine is a degradation product of the gut-brain peptide cholecystokinin-8 rather than angiotensin by the angiotensin-converting enzyme (odds ratio [OR] per SD increase [95% CI], 1.29 [1.13-1.48]; false discovery rate-adjusted P=0.025), 1,5-AG is a marker of short-term glycemic excursions (OR per SD increase [95% CI], 0.75 [0.64-to 0.87]; false discovery rate-adjusted P=0.025), and tetracosanoic acid is a very-long-chain saturated fatty acid (OR per SD increase [95% CI], 1.26 [1.10-1.45]; false discovery rate-adjusted P=0.091). Similar associations of 1,5-AG (OR per SD increase [95% CI], 0.77 [0.61-0.97]) and tetracosanoic acid (OR per SD increase [95% CI], 1.32 [1.06-1.67]) with coronary artery disease risk were observed in a subsample from an independent cohort (152 and 96 incident cases, respectively). Associations of aspartylphenylalanine and tetracosanoic acid were independent of traditional cardiovascular risk factors (P-trend=0.015 and 0.034, respectively). Furthermore, the association of aspartylphenylalanine was mediated by 13.92% from hypertension and 27.39% from dyslipidemia (P<0.05), supported by its causal links with hypertension (P<0.05) and hypertriglyceridemia (P=0.077) in Mendelian randomization analysis. The association of 1,5-AG with ACS risk was 37.99% mediated from fasting glucose, and genetically predicted 1,5-AG level was negatively associated with ACS risk (OR per SD increase [95% CI], 0.57 [0.33-0.96], P=0.036), yet the association was nonsignificant when further adjusting for fasting glucose. Conclusions These findings highlighted novel angiotensin-independent involvement of the angiotensin-converting enzyme in ACS cause, and the importance of glycemic excursions and very-long-chain saturated fatty acid metabolism.

Elevated Chinese visceral adiposity index increases the risk of stroke in Chinese patients with metabolic syndrome.

Patients with Metabolic Syndrome (MetS) are considered at high-risk for incident stroke. An indicator of visceral adiposity dysfunction, the Chinese Visceral Adiposity Index (CVAI) is used to evaluate the dysfunction of visceral fat. Given the impact of visceral adiposity dysfunction on elevating cardiovascular hazards, this study aimed to examine the association between CVAI and stroke risk in MetS patients. Between November 2017 and December 2018, a total of 18,974 individuals aged ≥40 underwent standardized in-person clinical interviews in Hunan Province, with 6,732 meeting the criteria for MetS. After the baseline survey was completed, subsequent surveys were conducted biennially. The study was split into two stages performed at baseline and after two years. During the former, receiver-operating characteristic curves were used to assess the accuracy of using baseline CVAI in diagnosing MetS. After two years, we examined the association between CVAI and incident stroke in MetS patients using logistic regression, subgroup analysis, and restricted cubic spline (RCS) analysis. As evidenced by a higher AUC (AUC:0.741), CVAI demonstrated superior diagnostic performance relative to body mass index (AUC:0.631) and waist circumference (AUC:0.627) in diagnosing MetS. After a 2-year follow-up, 72 MetS patients had a stroke event. There was a robust positive correlation between incident stroke and CVAI in patients with MetS. Each 1 SD increase in CVAI was associated with a 1.52-fold higher risk of stroke after adjustment for confounding factors (aOR=1.52, 95%CI: 1.18-1.95). The RCS demonstrated a reduced risk of stroke for MetS patients when the CVAI was below 110.91. However, no significant correlation was detected between CVAI and stroke in non-MetS patients. Our findings recommend CVAI as a superior screening tool for detecting MetS and suggest that reducing CVAI can mitigate the risk of stroke in patients with MetS.

The associations of ferritin, serum lipid and plasma glucose levels across pregnancy in women with gestational diabetes mellitus and newborn birth weight

BackgroundWomen with gestational diabetes mellitus (GDM) are at greater risk of abnormal birth weight. Since the level of biochemical indicators could often affect the intrauterine growth and development of the fetus, it is of great practical significance to understand the changes of biochemical levels across pregnancy in women with GDM and to find out the indicators that play an important role in predicting birth weight.MethodsThe data source of this study was from the Xi'an Longitudinal Mother–Child Cohort study (XAMC), in which women with GDM with normal and high pre-pregnancy body mass index (BMI) and their newborns between January 1st and March 31st in 2018 were included. The data of ferritin, serum lipid profile and fasting plasma glucose (FPG) of mothers in the three trimesters of pregnancy, as well as birth weight of newborns were all collected from medical records. Multiple linear regression and multivariate logistic regression analyses were used to explore the association of the biochemical indexes and birth weight. A P value < 0.05 was considered statistically significant.ResultsA total of 782 mother-infant pairs were finally included and divided into normal weight group (NG) (n = 530, 67.8%) and overweight/obesity group (OG) (n = 252, 32.2%) according to maternal pre-pregnancy BMI. The level of ferritin in both NG and OG decreased during pregnancy (P for trend < 0.001 for all), whereas the levels of total cholesterol (TC), high density cholesterol (HDL-C), low density cholesterol (LDL-C) and triglycerides (TG) all showed an upward trend (P for trend < 0.05 for all). The levels of FPG in the two groups remained in a relatively stable during the whole pregnancy even though it was higher in OG during the 2nd and 3rd trimesters, whilst HbAlc levels in NG women increased (P for trend = 0.043) during pregnancy. Meanwhile, the risk of macrosomia and large-for-gestational-age (LGA) increased with the increase of FPG level (P for trend < 0.05). Multivariate logistic regression analyses results showed that only FPG level in the 3rd trimester was correlated with birth weight, with birth weight increased by 44.9 g for each SD increase in FPG level.ConclusionMaternal FPG in the 3rd trimester is an independent predictor of newborn birth weight, and a higher level of that is associated with an increased risk of macrosomia and LGA.

Lung function and nonalcoholic fatty liver disease: a Mendelian randomization study

IntroductionAssociations of pulmonary function as evaluated by forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) with non-alcoholic fatty liver disease (NAFLD) have been reported in observational studies. Nevertheless, observational studies are susceptible to bias and reverse causality, making it difficult to infer the existence and direction of causality. We aimed to evaluate the causal effect of pulmonary function on NAFLD using the Mendelian randomization (MR) method.Material and methodsWe performed univariate MR, multivariate MR, and bidirectional two-sample MR analyses to jointly assess the causal relationship between pulmonary function and NAFLD. In addition to the inverse variance weighting method as the primary MR analysis, three complementary methods were also performed. A series of sensitivity analyses were carried out to rule out pleiotropy.ResultsWe found that each genetically predicted (standard deviation) SD increase in FEV1 and FVC was associated with decreased NAFLD risk. However, after adjusting for height in the multivariate MR, only the effect of FEV1 on NAFLD risk remained significant. Furthermore, we found no causal effect of NAFLD on lung function in the reverse MR analysis.ConclusionsOur findings indicated that reduced lung function, especially FEV1, is causally associated with the risk of NAFLD. Although the mechanism remains unclear, FEV1 could be considered when assessing NAFLD risk and as a potential target for NAFLD prevention.

Physical Activity, Sedentary Behavior, and Type 2 Diabetes: Mendelian Randomization Analysis.

The causality and pathways of the associations between physical activity and inactivity and the risk of type 2 diabetes remain inconclusive. We conducted an updated mendelian randomization (MR) study to explore the associations of moderate-to-vigorous physical activity (MVPA) and leisure screen time (LST) with type 2 diabetes mellitus (T2DM). Genetic variants strongly associated with MVPA or LST with low linkage disequilibrium were selected as instrumental variables from a genome-wide meta-analysis including more than 600 000 individuals. Summary-level data on T2DM were obtained from the DIAbetes Genetics Replication And Meta-analysis consortium including 898 130 individuals. Data on possible intermediates (adiposity indicators, lean mass, glycemic traits, and inflammatory biomarkers) were extracted from large-scale genome-wide association studies (n = 21 758-681 275). Univariable and multivariable MR analyses were performed to estimate the total and direct effects of MVPA and LST on T2DM. Methylation MR analysis was performed for MVPA in relation to diabetes. The odds ratio of T2DM was 0.70 (95% CI, 0.55-0.88; P = .002) per unit increase in the log-odds ratio of having MVPA and 1.45 (95% CI, 1.30-1.62; P = 7.62 × 10-11) per SD increase in genetically predicted LST. These associations attenuated in multivariable MR analyses adjusted for genetically predicted waist-to-hip ratio, body mass index, lean mass, and circulating C-reactive protein. The association between genetically predicted MVPA and T2DM attenuated after adjusting for genetically predicted fasting insulin levels. Two physical activity-related methylation biomarkers (cg17332422 in ADAMTS2 and cg09531019) were associated with the risk of T2DM (P < .05). The study suggests causal associations of MVPA and LST with T2DM that appear to be mediated by obesity, lean mass, and chronic low-grade inflammation.

Incremental value of epicardial fat volume on predicting obstructive coronary artery disease with myocardial ischemia

Objective: This study aimed to investigate the association between epicardial fat volume (EFV) and obstructive coronary artery disease (CAD) with myocardial ischemia, and evaluate the incremental value of EFV on top of traditional risk factors and coronary artery calcium (CAC) in predicting obstructive CAD with myocardial ischemia. Methods: This study was a retrospective cross-sectional study. Patients with suspected CAD who underwent coronary angiography (CAG) and single photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) at the Third Affiliated Hospital of Soochow University from March 2018 to November 2019 were consecutively enrolled. EFV and CAC were measured by non-contrast chest computed tomography (CT) scan. Obstructive CAD was defined as coronary artery stenosis≥50% in at least one of the major epicardial coronary arteries, and myocardial ischemia was defined as reversible perfusion defects in stress and rest MPI. Obstructive CAD with myocardial ischemia was defined in patients with coronary stenosis severity≥50% and reversible perfusion defects in the corresponding areas of SPECT-MPI. Patients with myocardial ischemia bot without obstructive CAD were defined as none-obstructive CAD with myocardial ischemia group. We collected and compared the general clinical data, CAC and EFV between the two groups. Multivariable logistic regression analysis was performed to identify the relationship between EFV and obstructive CAD with myocardial ischemia. ROC curves were performed to determine whether addition of EFV improved predictive value beyond traditional risk factors and CAC for obstructive CAD with myocardial ischemia. Results: Among the 164 patients with suspected CAD, 111 patients were males, and average age was (61.4±9.9) years old. 62 (37.8%) patients were included into the obstructive CAD with myocardial ischemia group. 102 (62.2%) patients were included into the none-obstructive CAD with myocardial ischemia group. EFV was significantly higher in obstructive CAD with myocardial ischemia group than in none-obstructive CAD with myocardial ischemia group ((135.63±33.29)cm3 and (105.18±31.16)cm3, P<0.01). Univariate regression analysis showed the risk of obstructive CAD with myocardial ischemia increased by 1.96 times for each SD increase in EFV(OR 2.96; 95%CI, 1.89-4.62; P<0.01). After adjustment for traditional risk factors and CAC, EFV remained as an independent predictor for obstructive CAD with myocardial ischemia (OR, 4.48, 95%CI, 2.17-9.23; P<0.01). Addition of EFV to CAC and traditional risk factors was related to larger AUC for predicting obstructive CAD with myocardial ischemia (0.90 vs. 0.85, P=0.04, 95%CI: 0.85-0.95) and the global chi-square increased by 21.81 (P<0.05). Conclusions: EFV is an independent predictor for obstructive CAD with myocardial ischemia. Addition of EFV to traditional risk factors and CAC has incremental value for predicting obstructive CAD with myocardial ischemia in this patient cohort.

Association of Polyunsaturated Fatty Acids and Clinical Progression in Patients With ALS: Post Hoc Analysis of the EMPOWER Trial.

Polyunsaturated fatty acids (PUFAs) have neuroprotective and anti-inflammatory effects and could be beneficial in amyotrophic lateral sclerosis (ALS). Higher dietary intake and plasma levels of PUFAs, in particular alpha-linolenic acid (ALA), have been associated with a lower risk of ALS in large epidemiologic cohort studies, but data on disease progression in patients with ALS are sparse. We examined whether plasma levels of ALA and other PUFAs contributed to predicting survival time and functional decline in patients with ALS. We conducted a study among participants in the EMPOWER clinical trial who had plasma samples collected at the time of randomization that were available for fatty acid analyses. Plasma fatty acids were measured using gas chromatography. We used Cox proportional hazards models and linear regression to evaluate the association of individual fatty acids with risk of death and joint rank test score of functional decline and survival. Fatty acid analyses were conducted in 449 participants. The mean (SD) age of these participants at baseline was 57.5 (10.7) years, and 293 (65.3%) were men; 126 (28.1%) died during follow-up. Higher ALA levels were associated with lower risk of death (age-adjusted and sex-adjusted hazard ratio comparing highest vs lowest quartile 0.50, 95% CI 0.29-0.86, p-trend = 0.041) and higher joint rank test score (difference in score according to 1 SD increase 10.7, 95% CI 0.2-21.1, p = 0.045), consistent with a slower functional decline. The estimates remained similar in analyses adjusted for body mass index, race/ethnicity, symptom duration, site of onset, riluzole use, family history of ALS, predicted upright slow vital capacity, and treatment group. Higher levels of the n-3 fatty acid eicosapentaenoic acid and the n-6 fatty acid linoleic acid were associated with a lower risk of death during follow-up. Higher levels of ALA were associated with longer survival and slower functional decline in patients with ALS. These results suggest that ALA may have a favorable effect on disease progression in patients with ALS.

Greater intramuscular adipose tissue of the quadriceps in older inpatients at post-acute hospital admission is more strongly related to a low rate of home discharge than a loss of muscle mass

This study aimed to examine the relationships between intramuscular adipose tissue and muscle mass of the quadriceps at post-acute hospital admission and the low rate of home discharge. This prospective study included 389 inpatients aged ≥ 65 years. Patients were divided into two groups according to the destination: home discharge (n = 279) and no-home discharge (n = 110) groups. The primary outcome was hospital discharge destination (home discharge or not). Intramuscular adipose tissue and muscle mass of the quadriceps were assessed at post-acute hospital admission using echo intensity and muscle thickness on ultrasound images, respectively. Logistic regression analysis was used for determining whether quadriceps echo intensity is related to home discharge. Quadriceps echo intensity was significantly and independently associated with home discharge (odds ratio [per 1 SD increase] = 1.43, p = 0.045). Quadriceps thickness was not associated with home discharge (odds ratio [per 1 SD increase] = 1.00, p = 0.998). Our study indicates that greater intramuscular adipose tissue of the quadriceps in older inpatients at post-acute hospital admission is more strongly related to a low rate of home discharge than a loss of muscle mass.

342-OR: The Impact of Insulin Secretion and Insulin Sensitivity on Cognition in Adults with Prediabetes—The Diabetes Prevention Program Outcomes Study (DPPOS)

Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant of dysglycemia, impaired insulin sensitivity (ISens) or insulin secretion (ISecr), or both, contributes to poorer cognitive function is not established. Among 1,054 adults with prediabetes (PreD) from the DPPOS, who did not develop diabetes, we investigated the relationship between ISecr, ISens and cognitive function, hypothesizing that lower ISens and/or lower ISecr is associated with worse cognition. Early ISecr was estimated by the mean insulinogenic index (IGI; pmol/mmol) from repeated annual oral glucose tolerance tests and ISens was estimated by the mean 1/fasting insulin from repeated fasting blood draws. ISecr and ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and processing speed (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Separate linear regression models were run for each cognitive outcome. Models included both mean ISecr and mean ISens as the main predictor variables and were adjusted for demographic, lifestyle, cardiovascular factors, and medications. Contrary to our hypothesis and to prior studies, higher mean ISecr was associated with poorer performance on the DSST (-0.74 points per SD increase in IGI, 95% CI: -1.43, -0.05; p=0.03). Mean ISens was not associated with DSST, nor were mean ISecr or mean ISens associated with SEVLT. These results suggest that higher insulin secretion in people with longstanding PreD may negatively impact processing speed, a critical component of executive control. This relationship could reflect a compensatory response of insulin in people with worsening metabolic dysregulation, who may also have poorer cognition. Further study is needed to replicate these findings and to understand the role of insulin in cognitive function. Disclosure A. Shapiro: None. A.H. Tjaden: None. S. Edelstein: None. S.E. Kahn: Advisory Panel; Anji Pharmaceuticals, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck &amp; Co., Inc. Other Relationship; Novo Nordisk. P. Srikanthan: None. W.C. Knowler: None. E.M. Venditti: None. S. Golden: Advisory Panel; Abbott Diabetes, Medtronic. O. Carmichael: Research Support; Eli Lilly and Company. Advisory Panel; Novo Nordisk. Research Support; Nestlé Health Science. K.M. Gadde: Research Support; BioKier, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. J.A. Luchsinger: Consultant; Merck KGaA. Other Relationship; Wolters Kluwer Health. D. Research Group: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UDK048489, UDK048339, UDK048377, UDK048349, UDK048381, UDK048468, UDK048434, UDK048485, UDK048375, UDK048514, UDK048437, UDK048413, UDK048411, UDK048406, UDK048380, UDK048397, UDK048412, UDK048404, UDK048387, UDK048407, UDK048443, UDK048400)

The relation between left atrial and left ventricular size in a healthy population

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The project was funded by grants from The Liaison Committee for Education, Research and Innovation in Central Norway, St. Olavs University Hospital (Trondheim, Norway), Nord-Trøndelag Hospital Trust (Levanger, Norway), and Simon Fougner Hartmann's Family Fund (Copenhagen, Denmark). Background The left atrium (LA) and ventricle (LV) are closely linked and adapt to meet metabolic demands. Reduced LV end-diastolic volume (LVEDV) and increased LA end-systolic volume (LAESV) is common in patients with diastolic dysfunction and with higher age. The remodeling of LA and LV in response to endurance exercise is thought to be balanced, and thus, the LA:LV ratio could help discriminate pathologic from physiologic LA enlargement. Purpose We aimed to describe the relative LA and LV chamber remodeling associated with the clinical characteristics age, sex, maximal oxygen consumption (VO2peak), HbA1C, body mass index, systolic blood pressure, and diastolic dysfunction. Methods Healthy participants included in a large longitudinal population study underwent clinical evaluation and cardiopulmonary exercise testing (CPET) in 2006–2008, followed by comprehensive echocardiography and CPET in 2017–18. Exclusion criteria were: 1) submaximal performance during CPET, 2) atrial fibrillation, or 3) presence of heart failure or a history of myocardial infarction. All examinations were performed by highly experienced personnel. All echocardiographic exams and analyses were performed by personnel affiliated a European Association of Cardiovascular Imaging accredited echo-laboratory. Results In total, 1,349 participants were included. Mean (SD) age was 58 (12) years, and 52% were women. The LA:LV ratio was higher with higher age due to lower LVEDV and stable LAESV (Figure 1). Age alone explained 12% (p&amp;lt;0.001) of variance for the LA:LV ratio and men had higher LA:LV ratios than women (0.55 vs. 0.50, p &amp;lt;0.001). All examined clinical characteristics showed significant associations with LA:LV ratios in univariate regression analyses. In adjusted analyses, increased VO2peak was significantly associated with increased LA:LV ratio, but with a small effect-size without clinical significance. In the subsample with indexed LAESV &amp;gt;34mL/m2, increased VO2peak was significantly associated with increased LA:LV-ratio in adjusted analyses (p &amp;lt;0.001). Ten-year change in VO2peak was not significantly associated with LA:LV ratio in adjusted models for the total population, nor in the subgroup with indexed LAESV &amp;gt;34 mL (p = 0.181). Multiple logistic regression showed that higher LA:LV ratio was associated with increased risk of diastolic dysfunction with an OR (95% CI) of 2.4 (1.5, 4.0) per SD increase in LA:LV-ratio, adjusted for age, sex, systolic blood pressure, HbA1c, and BMI (p &amp;lt; 0.001). LA strain measures, E/e’ ratio, and TR velocity were significantly associated with the LA:LV ratio, while other diastolic function parameters were not. Conclusion The LA:LV ratio increases with higher age due to reduced LVEDV and stable LAESV. VO2peak was not a robust predictor of LA:LV ratio in this population. Future studies should evaluate the relative remodeling of LA and LV with repeated measurements of echocardiographic indices and CPET to better define the role of this ratio.

Prospective Study of Associations Between Testosterone, Mortality, and Health Outcomes Among Adults Undergoing Hemodialysis

Prospective Study of Associations Between Testosterone, Mortality, and Health Outcomes Among Adults Undergoing Hemodialysis

Association between family caregivers' primary care experience when they report as patients and their stress related to caregiving: A pilot cross-sectional study.

Few studies have examined whether family caregivers' own primary care providers can affect caregiving-specific well-being, such as caregiver stress. In this pilot study, we explored whether primary care experiences when family caregivers report as patients were associated with the stress of caregiving. We used cross-sectional data from a survey conducted in Japan between November and December 2020. We recruited family caregivers aged 40-74 years who were caring for community-dwelling adults with chronic conditions. We assessed primary care experience using the Japanese version of the Primary Care Assessment Tool Short Form (JPCAT-SF) and caregiver stress using the Japanese short version of the Zarit Caregiver Burden Interview. In total, 406 family caregivers were included in the analysis. The mean JPCAT-SF total score was 42.1 out of 100 points. The proportion of caregivers who had higher caregiver stress was 48.8%. After adjusting for possible confounders, the JPCAT-SF score was found to be significantly associated with caregiver stress (lower stress = 0 vs. higher stress = 1; adjusted prevalence ratio per 1 SD increase in JPCAT-SF score = 0.89; 95% CI 0.80-0.98). Among the subscales of the JPCAT-SF, longitudinality, and comprehensiveness (services available) were associated with caregiver stress. Better primary care experiences when family caregivers reported as patients were associated with lower caregiver stress. Longitudinality, which includes focusing attention on the individual as a whole person, and comprehensiveness in the context of building provider-patient relationships that make consultation easier when needed, were associated with lower stress.

Development of a Breast Cancer Risk Prediction Model Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Korean Women.

To develop a breast cancer prediction model for Korean women using published polygenic risk scores (PRS) combined with nongenetic risk factors (NGRF). Thirteen PRS models generated from single or multiple combinations of the Asian and European PRSs were evaluated among 20,434 Korean women. The AUC and increase in OR per SD were compared for each PRS. The PRSs with the highest predictive power were combined with NGRFs; then, an integrated prediction model was established using the Individualized Coherent Absolute Risk Estimation (iCARE) tool. The absolute breast cancer risk was stratified for 18,142 women with available follow-up data. PRS38_ASN+PRS190_EB, a combination of Asian and European PRSs, had the highest AUC (0.621) among PRSs, with an OR per SD increase of 1.45 (95% confidence interval: 1.31-1.61). Compared with the average risk group (35%-65%), women in the top 5% had a 2.5-fold higher risk of breast cancer. Incorporating NGRFs yielded a modest increase in the AUC of women ages >50 years. For PRS38_ASN+PRS190_EB+NGRF, the average absolute risk was 5.06%. The lifetime absolute risk at age 80 years for women in the top 5% was 9.93%, whereas that of women in the lowest 5% was 2.22%. Women at higher risks were more sensitive to NGRF incorporation. Combined Asian and European PRSs were predictive of breast cancer in Korean women. Our findings support the use of these models for personalized screening and prevention of breast cancer. Our study provides insights into genetic susceptibility and NGRFs for predicting breast cancer in Korean women.

Carotid geometry is independently associated with complicated carotid artery plaques.

Complicated carotid artery plaques (cCAPs) are associated with an increased risk of rupture and subsequent stroke. The geometry of the carotid bifurcation determines the distribution of local hemodynamics and could thus contribute to the development and composition of these plaques. Therefore, we studied the role of carotid bifurcation geometry in the presence of cCAPs. We investigated the association of individual vessel geometry with carotid artery plaque types in the Carotid Plaque Imaging in Acute Stroke (CAPIAS) study. After excluding arteries without plaque or with insufficient MRI quality, 354 carotid arteries from 182 patients were analyzed. Individual parameters of carotid geometry [i.e., internal carotid artery (ICA)/common carotid artery (CCA) ratio, bifurcation angle, and tortuosity) were derived from time-of-flight MR images. The lesion types of carotid artery plaques were determined according to the American Heart Association classification of lesions by multi-contrast 3T-MRI. The association between carotid geometry and a cCAP was studied using logistic regression after adjusting for age, sex, wall area, and cardiovascular risk factors. Low ICA/CCA ratios (OR per SD increase 0.60 [95%CI: 0.42-0.85]; p = 0.004) and low bifurcation angles (OR 0.61 [95%CI: 0.42-0.90]; p = 0.012) were significantly associated with the presence of cCAPs after adjusting for age, sex, cardiovascular risk factors, and wall area. Tortuosity had no significant association with cCAPs. Only ICA/CCA ratio remained significant in a model containing all three geometric parameters (OR per SD increase 0.65 [95%CI: 0.45-0.94]; p = 0.023). A steep tapering of the ICA relative to the CCA and, to a lesser extent, a low angle of the carotid bifurcation were associated with the presence of cCAPs. Our findings highlight the contribution of bifurcation geometry to plaque vulnerability. Thus, assessment of carotid geometry could be helpful in identifying patients at risk of cCAPs.

The association between brachial-ankle pulse-wave velocity and adverse cardiovascular events in 5719 community participants a prospective cohort study.

The brachial-ankle pulse-wave velocity (baPWV) is regarded as the gold standard in the evaluation of arterial stiffness. Its prognostic significance for major adverse cardiovascular events (MACE) has been demonstrated. However, the factors influencing the association between baPWV and MACE risk have not been determined. In this study, we investigated the association of baPWV and MACE risk and whether it is affected by the risk factors for different cardiovascular diseases (CVDs). This was a prospective cohort study that initially enrolled 6850 participants from 12 communities in Beijing. The participants were divided into three subgroups according to their baPWV values. The primary outcome was the first occurrence of MACE, defined as hospitalization from cardiovascular diseases, first occurrence of a nonfatal myocardial infarction, or nonfatal stroke. Cox proportional hazards regression and restricted cubic spline analyses were used to examine the association between baPWV and MACE. The effect of CVD risk factors on the relationship between baPWV and MACE was explored in subgroup analyses. The final study population consisted of 5719 participants. During a median follow-up of 34.73 months, MACE occurred in 169 participants. The restricted cubic spline analysis indicated a positive linear relationship between baPWV and MACE risk. After adjustment for cardiovascular risk factors, the hazard ratio (HR) for MACE risk per SD increase in baPWV was 1.272 [95% confidence interval (CI): 1.149-1.407, P < 0.001], and the HR for MACE in the high-baPWV vs. the low-baPWV group was 1.965 (95% CI: 1.296-2.979, P = 0.001). Adding baPWV to the conventional cardiovascular risk factors significantly improved the model's prediction performance and the net reclassification (NRI) [NRI: 0.379 (95% CI: 0.072-0.710), P = 0.025] in MACE discrimination. However, in the subgroup analysis, two CVD risk factors, stable coronary heart disease and hypertension, showed significant interaction effects (Pinteraction both < 0.05). This result indicated that the effect of CVD risk factors must be taken into account when assessing the relationship between baPWV and MACE. baPWV is a potential marker to improve the identification of MACE risk in the general population. A positive linear correlation was firstly determined between baPWV and MACE risk, but it may not be valid in participants with stable coronary heart disease and hypertension.

Racial and ethnic differences in the availability of community medical services after leaving prison

IntroductionIncarcerated individuals experience increased health problems, presenting additional challenges as they leave prison and re-enter the community. These challenges are disproportionally experienced by racial and ethnic minorities. Despite these trends,...

Cumulative Genetic Score and C9orf72 Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies.

Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores. Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion. Final cohort size was 219 ALS and 223 healthy controls after genotyping and participant filtering. Polygenic scores excluding the C9 region were generated using an independent ALS genome-wide association study (20,806 cases, 59,804 controls). Adjusted logistic regression and receiver operating characteristic curves evaluated the association and classification between polygenic scores and ALS status, respectively. Population attributable fractions and pathway analyses were conducted. An independent Spanish study sample (548 cases, 2,756 controls) was used for replication. Polygenic scores constructed from 275 single-nucleotide variation (SNV) had the best model fit in the Michigan cohort. An SD increase in ALS polygenic score associated with 1.28 (95% CI 1.04-1.57) times higher odds of ALS with area under the curve of 0.663 vs a model without the ALS polygenic score (p value = 1 × 10-6). The population attributable fraction of the highest 20th percentile of ALS polygenic scores, relative to the lowest 80th percentile, was 4.1% of ALS cases. Genes annotated to this polygenic score enriched for important ALS pathomechanisms. Meta-analysis with the Spanish study, using a harmonized 132 single nucleotide variation polygenic score, yielded similar logistic regression findings (odds ratio: 1.13, 95% CI 1.04-1.23). ALS polygenic scores can account for cumulative genetic risk in populations and reflect disease-relevant pathways. If further validated, this polygenic score will inform future ALS risk models.

Heart rate variability is associated with global cognition and cognitive impairment: Results from the einstein aging study

AbstractBackgroundThe role of autonomic function in cognitive impairment is unclear. Heart rate variability (HRV) provides a feasible, non‐invasive measure of cardiac autonomic control. We examined whether HRV is associated with global cognition and cognitive impairment using 7‐day ambulatory ECG assessments in the Einstein Aging Study.MethodAnalyses included 84 participants free of dementia (mean age 78.1 (± 5.2) years; 82% female; 39% non‐Hispanic White, 44% non‐Hispanic Black, mean education 14.7 (± 3.3 years)). Participants wore a small, single lead ECG device continuously over 7 days. Power spectral analyses were applied to determine HRV over 5‐minute epochs in the high (0.15‐0.40 Hz, hfHRV) and low (0.04‐0.15 Hz, lfHRV) frequency bands, and values were log transformed. Demographics, comorbidities, and cognition were assessed during clinic visits. Two tests per domain evaluated memory, executive function, language, visuo‐spatial and attention with impairment defined as performance ≥ 1.5 SD below the age, sex, education standardized norm on at least one test. Global cognition was assessed using the MoCA, and Mild Cognitive Impairment (MCI) was defined using Jak‐Bondi criteria. Associations of HRV with cognition were examined using logistic (MCI, domain specific impairment) and linear (MoCA) regression adjusting for age, sex, race/ethnicity and education, diabetes, and hypertension.ResultMean MoCA score was 24 (SD 3.5), 21 (25%) had MCI and impairment was identified in 25% (memory), 28.6% (executive function), 21.4% (attention), 17.9% (language) and 27.4% (visuospatial). Both hfHRV and lfHRV were inversely associated with MCI (OR per 1 SD increase in log HRV: 0.47, p = 0.02 for hfHRV and 0.42, p = 0.01 for lfHRV) and with memory impairment (OR per 1 SD increase in log HRV: 0.52, p = 0.03 for hfHRV and 0.43, p = 0.01 for lfHRV). Higher hfHRV and lfHRV were each associated with better MoCA score (β for 1 SD increase in log HRV: 0.65, p = 0.046 for hfHRV; 0.80, p = 0.02).ConclusionWhether HRV is associated with cognitive impairment remains unclear, particularly the role of hfHRV, indicative of parasympathetic control. Findings suggest that hfHRV is related to cognitive performance and impairment. Results for lfHRV also suggest joint effects of the sympathetic and parasympathetic systems.

Integrated actigraphy‐based biomarker for Alzheimer’s dementia progression

AbstractBackgroundActigraphy derived measures including amplitude, regularity, and variability of daily rhythm, have been shown to predict incident Alzheimer’s dementia. Here we developed an integrated actigraphy biomarker (IAB) for Alzheimer’ risk and investigated whether the IAB predicted the conversion from mild cognitive impairment (MCI) to Alzheimer’ dementia.MethodWe studied 1195 participants (age 80.8±7.2yrs [SD]) from the Rush Memory and Aging Project who had finished baseline actigraphy assessment (∼10 days), were free from Alzheimer’s dementia at actigraphy baseline and had been followed for up to 15 years with annual cognitive assessment and clinical diagnoses. Ten sleep/circadian related features were derived from baseline actigraphy recordings and were fed into a random forest survival model for prediction of time and incident Alzheimer’s dementia. IAB was derived from the model as the relative risk. Cox proportional hazards and logistic regression models were used to evaluate the performance of IAB in predicting incident Alzheimer’s dementia (all 1195 participants) or MCI (858 without MCI at baseline) and predicting the conversion from MCI to Alzheimer’s dementia. Demographic variables including age, sex, and education were controlled in all Cox and logistic regression models.ResultTotal 287 participants developed Alzheimer’s dementia during the follow‐up. The derived IAB was 0.6 SD larger in the participants developed Alzheimer’s dementia as compared with the controls. Larger IAB was associated with increased risk of AD with a hazard ratio (HR) = 1.63 (95% CI = 1.46‐1.81, P&lt;0.0001) for 1‐SD increase in IAB. IAB did not predict incident MCI (P = 0.8). Within participants with MCI (337 at baseline and 308 developed), larger IAB was associated with a higher risk for AD, i.e., HR = 1.34 for 1 SD increase (95% CI = 1.18‐1.51, P&lt;0.0001). The logistic model using the cutoff of 3 years for the MCI‐Alzheimer’s dementia conversion gives the odd ratio = 1.56 for 1 SD increase of IAB, and results in AUC = 0.68, with a sensitivity = 0.68 and specificity = 0.61.ConclusionDerived actigraphy biomarker was predictive of Alzheimer’s risk at preclinical stages, and the conversion from MCI. Actigraphy provides useful information for early prediction and detection of AD thought its performance needs to be improved.

Plasma Neurofilament Light (NfL) associated with retest learning effects on ambulatory cognitive assessments of processing speed: Results from the Einstein Aging Study (EAS)

AbstractBackgroundMeasurement burst designs, using ambulatory cognitive assessments facilitate the dissociation of retest effects from optimal (“asymptotic”) performance. Dissociating these features via cognitive process modeling may reveal indices of subtle cognitive impairment that signal risk for neurocognitive decline. We investigated cross‐sectional associations between plasma NfL (a biomarker of neurodegeneration), retest improvements, and optimal performance on the Symbol Match task, which assesses processing speed by response time (RT), in a racially/ethnically diverse community‐based EAS Study cohort.MethodAnalyses included 283 EAS participants free of dementia (Mean age = 77.4 years, SD = 4.8, Range = 70‐91; 67% Female; 46% Non‐Hispanic White, 40% Non‐Hispanic Black). Among them, 82 met the Jak/Bondi criteria of mild cognitive impairment (MCI). Participants completed a smartphone cognitive battery, resulting in up to 96 assessment sessions (six times per day for 16 days). Plasma NfL concentration was measured using a Single molecule array assay. A mixed‐effect negative exponential model was used to examine the associations between plasma NfL and indices of subtle cognitive impairment adjusting for covariates including age, gender, education, and race/ethnicity. Retest improvement was measured by the exponential decrease in RT across sessions and optimal performance was measured by asymptotic RT (fastest performance).ResultOn average, the RT of the Symbol Match task was 3.4 seconds (SD = 0.9). Mean plasma NfL level was 23.9 pg/mL (SD = 17.5). Higher plasma NfL levels were associated with a reduced retest improvement rate per session (estimate = ‐0.011, 95% confidence interval (‐0.013, ‐0.008) corresponding to one SD increase in plasma NfL, p&lt;0.001). No significant association between plasma NfL and optimal cognitive performance was found. Stratified analyses showed NfL’s association with retest improvement was larger in non‐Hispanic Whites than in non‐Hispanic Blacks (‐0.009 vs ‐0.002), although formal testing of the interaction between NfL and race was not significant. Results remained very similar excluding participants with MCI.ConclusionHigher plasma NfL was associated with a reduced retest improvement rate on a smartphone processing speed task, highlighting its potential value for identifying subtle cognitive impairment. Longitudinal data from larger samples, a broader array of biomarkers and of ambulatory cognitive tests, are required to fully explore these issues.