The Importance of Mid-to-Late-Life Body Mass Index Trajectories on Late-Life Gait Speed

Background: Prior studies suggest being overweight may be protective against poor functional outcomes in older adults. Methods: Body mass index (BMI, kg/m2) was measured over 25 years across five visits (1987-2011) among Atherosclerosis Risk in Communities Study participants (baseline Visit 1 n = 15,720, aged 45-64 years). Gait speed was measured at Visit 5 ("late-life", aged ≥65 years, n = 6,229). BMI trajectories were examined using clinical cutpoints and continuous mixed models to estimate effects of patterns of BMI change on gait speed, adjusting for demographics and comorbidities. Results: Mid-life BMI (baseline visit; 55% women; 27% black) was associated with late-life gait speed 25 years later; gait speeds were 94.3, 89.6, and 82.1 cm/s for participants with baseline normal BMI (<25), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30) (p < .001). In longitudinal analyses, late-life gait speeds were 96.9, 88.8, and 81.3 cm/s for participants who maintained normal, overweight, and obese weight status, respectively, across 25 years (p < .01). Increasing BMI over 25 years was associated with poorer late-life gait speeds; a 1%/year BMI increase for a participant with a baseline BMI of 22.5 (final BMI 28.5) was associated with a 4.6-cm/s (95% confidence interval: -7.0, -1.8) slower late-life gait speed than a participant who maintained a baseline BMI of 22.5. Conclusion: Being overweight in older age was not protective of mobility function. Maintaining a normal BMI in mid- and late-life may help preserve late-life mobility

Physical activity trajectories and subsequent fall risk: ARIC Study

To examine the impact of moderate to vigorous intensity physical activity (MVPA) trajectories during midlife and older adulthood with subsequent fall risk in later life. Cross-temporal analyses were conducted in 15,792 participants (27% black, 55% women) aged 45 to 64 years enrolled in the Atherosclerosis Risk in Communities (ARIC) Study. MVPA was collected at Exams 1 (1987–89), 3 (1993–95) and 5 (2011–13) using the ARIC/Baecke questionnaire. Latent class growth analysis was used to identify the MVPA trajectory groups. Reported falls outcomes were collected in 2013–14, 2015–16, and 2016–17. Generalized Linear Models were used to estimate associations of baseline predictors with trajectory class membership, as well as associations of trajectory classes with any falling (adjusted incident relative risks, aIRR) and with number of falls (adjusted relative rates, aRR). Four primary trajectory classes emerged, reflecting longitudinal patterns of maintained high (48%), maintained low (22%), increasing (14%) and decreasing (15%) MVPA. After adjustment for covariates, the decreasing MVPA trajectory group had a 14% higher risk of reporting any falling compared to the maintained high MVPA group [aIRR = 1.14 (1.01, 1.28)]. When compared to the maintained high MVPA group, the maintained low and decreasing group had a 28% [aRR = 1.28 (1.14, 1.44)] and 27% [aRR = 1.27 (1.17, 1.38)] higher rate in the reported number of falls, respectively. Findings support public health campaigns targeting habitual MVPA or exercise for fall prevention and suggest that interventions should be initiated in midlife; a time when individuals may be more able and willing to change behavior

Electrocardiographic Predictors of Coronary Heart Disease and Sudden Cardiac Deaths in Men and Women Free From Cardiovascular Disease in the Atherosclerosis Risk in Communities Study

BackgroundWe evaluated predictors of coronary heart disease (CHD) death and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) study.Methods and ResultsThe study population included 13 621 men and women 45 to 65 years of age free from manifest cardiovascular disease at entry. Hazard ratios from Cox regression with 95% confidence intervals were computed for 18 dichotomized repolarization‐related ECG variables. The average follow‐up was 14 years. Independent predictors of CHD death in men were TaVR‐ and rate‐adjusted QTend (QTea), with a 2‐fold increased risk for both, and spatial angles between mean QRS and T vectors and between Tpeak (Tp) and normal R reference vectors [θ(Rm|Tm) and θ(Tp|Tref), respectively], with a >1.5‐fold increased risk for both. In women, independent predictors of the risk of CHD death were θ(Rm|Tm), with a 2‐fold increased risk for θ(Rm|Tm), and θ(Tp|Tref), with a 1.7‐fold increased risk. Independent predictors of SCD in men were θ(Tp|Tref) and QTea, with a 2‐fold increased risk, and θ(Tinit|Tterm), with a 1.6‐fold increased risk. In women, θ(Tinit|Tterm) was an independent predictor of SCD, with a >3‐fold increased risk, and θ(Rm|Tm) and TV1 were >2‐fold for both.Conclusionsθ(Rm|Tm) and θ(Tp|Tref), reflecting different aspects of ventricular repolarization, were independent predictors of CHD death and SCD, and TaVR and TV1 were also independent predictors. The risk levels for independent predictors for both CHD death and SCD were stronger in women than in men, and QTea was a significant predictor in men but not in women

Blood-stage antiplasmodial activity and oocyst formation-blockage of metallo copper-cinchonine complex

In the fight against malaria, the key is early treatment with antimalarial chemotherapy, such as artemisinin-based combination treatments (ACTs). However, Plasmodium has acquired multidrug resistance, including the emergence of P. falciparum strains with resistance to ACT. The development of novel antimalarial molecules, that are capable of interfering in the asexual and sexual blood stages, is important to slow down the transmission in endemic areas. In this work, we studied the ability of the mettalo copper-cinchonine complex to interfere in the sexual and asexual stages of Plasmodium. The tested compound in the in vitro assay was a cinchonine derivative, named CinCu (Bis[Cinchoninium Tetrachlorocuprate(II)]trihydrate). Its biological functions were assessed by antiplasmodial activity in vitro against chloroquine-resistant P. falciparum W2 strain. The mice model of P. berghei ANKA infection was used to analyze the antimalarial activity of CinCu and chloroquine and their acute toxicity. The oocyst formation-blocking assay was performed by experimental infection of Anopheles aquasalis with P. vivax infected blood, which was treated with different concentrations of CinCu, cinchonine, and primaquine. We found that CinCu was able to suppress as high as 81.58% of parasitemia in vitro, being considered a molecule with high antiplasmodial activity and low toxicity. The in vivo analysis showed that CinCu suppressed parasitemia at 34% up to 87.19%, being a partially active molecule against the blood-stage forms of P. berghei ANKA, without inducing severe clinical signs in the treated groups. The transmission-blocking assay revealed that both cinchonine and primaquine were able to reduce the infection intensity of P. vivax in A. aquasalis, leading to a decrease in the number of oocysts recovered from the mosquitoes’ midgut. Regarding the effect of CinCu, the copper-complex was not able to induce inhibition of P. vivax infection; however, it was able to induce an important reduction in the intensity of oocyst formation by about 2.4 times. It is plausible that the metallo-compound also be able to interfere with the differentiation of parasite stages and/or ookinete-secreted chitinase into the peritrophic matrix of mosquitoes, promoting a reduction in the number of oocysts formed. Taken together, the results suggest that this compound is promising as a prototype for the development of new antimalarial drugs. Furthermore, our study can draw a new pathway for repositioning already-known antimalarial drugs by editing their chemical structure to improve the antimalarial activity against the asexual and sexual stages of the parasite

Prognostic Variation Among Very High-Risk and High-Risk Individuals With Atherosclerotic Cardiovascular Disease

Given the availability of an effective but expensive lipid-lowering medication, proprotein convertase subtilisin/kexin type 9 inhibitors, the American Heart Association and the American College of Cardiology 2018 cholesterol guideline introduced a new classification of “very high-risk” (i.e., multiple major atherosclerotic cardiovascular diseases [ASCVDs] or a major ASCVD þ multiple high-risk conditions) versus “high-risk” for patients with prior ASCVD. A few recent studies reported risk variation within very high-risk ASCVD, with multiple ASCVDs conferring higher risk than 1 ASCVD þ $2 high-risk conditions. However, these studies did not evaluate whether the constellation of high-risk conditions in 1 ASCVD may equate to the risk of multiple ASCVDs or whether the new classification has implications for heart failure

Albuminuria and Prognosis Among Individuals With Atherosclerotic Cardiovascular Disease: The ARIC Study

The American College of Cardiology and the American Heart Association 2018 Cholesterol Guideline proposed the new classification of “very high-risk” atherosclerotic cardiovascular disease (ASCVD) (multiple ASCVDs or 1 ASCVD plus $2 high-risk conditions) to guide intensive secondary prevention. This guideline takes into account reduced glomerular filtration rate (GFR) as a high-risk condition, but not albuminuria, a measure of kidney damage, that is more strongly associated with cardiovascular outcomes than reduced GFR. Importantly, the assessment of albuminuria is already recommended in patients with diabetes and hypertension, and thus, data of albuminuria are readily available in many patients with ASCVD. We explored whether urine albumin-to-creatinine ratio (ACR) is independently associated with adverse outcomes and can improve risk prediction in persons with ASCVD beyond the high-risk conditions in the guideline

Cardiovascular Health and Incident Cardiovascular Disease and Cancer

The American Heart Association's “Simple 7” offers a practical public health conceptualization of cardiovascular health (CVH). CVH predicts incident cardiovascular disease (CVD) in younger populations, but has not been studied in a large, diverse population of aging postmenopausal women. The extent to which CVH predicts cancer in postmenopausal women is unknown

Hospital recruitment for a pragmatic cluster-randomized clinical trial: Lessons learned from the COMPASS study

Abstract Background Pragmatic randomized clinical trials are essential to determine the effectiveness of interventions in “real-world” clinical practice. These trials frequently use a cluster-randomized methodology, with randomization at the site level. Despite policymakers’ increased interest in supporting pragmatic randomized clinical trials, no studies to date have reported on the unique recruitment challenges faced by cluster-randomized pragmatic trials. We investigated key challenges and successful strategies for hospital recruitment in the Comprehensive Post-Acute Stroke Services (COMPASS) study. Methods The COMPASS study is designed to compare the effectiveness of the COMPASS model versus usual care in improving functional outcomes, reducing the numbers of hospital readmissions, and reducing caregiver strain for patients discharged home after stroke or transient ischemic attack. This model integrates early supported discharge planning with transitional care management, including nurse-led follow-up phone calls after 2, 30, and 60 days and an in-person clinic visit at 7–14 days involving a functional assessment and neurological examination. We present descriptive statistics of the characteristics of successfully recruited hospitals compared with all eligible hospitals, reasons for non-participation, and effective recruitment strategies. Results We successfully recruited 41 (43%) of 95 eligible North Carolina hospitals. Leading, non-exclusive reasons for non-participation included: insufficient staff or financial resources (n = 33, 61%), lack of health system support (n = 16, 30%), and lack of support of individual decision-makers (n = 11, 20%). Successful recruitment strategies included: building and nurturing relationships, engaging team members and community partners with a diverse skill mix, identifying gatekeepers, finding mutually beneficial solutions, having a central institutional review board, sharing published pilot data, and integrating contracts and review board administrators. Conclusions Although we incorporated strategies based on the best available evidence at the outset of the study, hospital recruitment required three times as much time and considerably more staff than anticipated. To reach our goal, we tailored strategies to individuals, hospitals, and health systems. Successful recruitment of a sufficient number and representative mix of hospitals requires considerable preparation, planning, and flexibility. Strategies presented here may assist future trial organizers in implementing cluster-randomized pragmatic trials. Trial registration Clinicaltrials.gov, NCT02588664 . Registered on 23 October 2015

Differences in incident and recurrent myocardial infarction among White and Black individuals aged 35 to 84: Findings from the ARIC community surveillance study

Background: No previous study has examined racial differences in recurrent acute myocardial infarction (AMI) in a community population. We aimed to examine racial differences in recurrent AMI risk, along with first AMI risk in a community population. Methods: The community surveillance of the Atherosclerosis Risk in Communities Study (2005-2014) included 470,000 people 35 to 84 years old in 4 U.S. communities. Hospitalizations for recurrent and first AMI were identified from ICD-9-CM discharge codes. Poisson regression models were used to compare recurrent and first AMI risk ratios between Black and White residents. Results: Recurrent and first AMI risk per 1,000 persons were 8.8 (95% CI, 8.3-9.2) and 20.7 (95% CI, 20.0-21.4) in Black men, 6.8 (95% CI, 6.5-7.0) and 14.1 (95% CI, 13.8-14.5) in White men, 5.3 (95% CI, 5.0-5.7) and 16.2 (95% CI, 15.6-16.8) in Black women, and 3.1 (95% CI, 3.0-3.3) and 8.8 (95% CI, 8.6-9.0) in White women, respectively. The age-adjusted risk ratios (RR) of recurrent AMI were higher in Black men vs White men (RR, 1.58 95% CI, 1.30-1.92) and Black women vs White women (RR, 2.09 95% CI, 1.64-2.66). The corresponding RRs were slightly lower for first AMI: Black men vs White men, RR, 1.49 (95% CI, 1.30-1.71) and Black women vs White women, RR, 1.65 (95% CI, 1.42-1.92) Conclusions: Large disparities exist by race for recurrent AMI risk in the community. The magnitude of disparities is stronger for recurrent events than for first events, and particularly among women