The effect of long-term adherence to physical activity recommendations in midlife on plasma proteins associated with frailty in the Atherosclerosis Risk in Communities (ARIC) study.

Clinical trials have shown favorable effects of exercise on frailty, supporting physical activity (PA) as a treatment and prevention strategy. Proteomics studies suggest that PA alters levels of many proteins, some of which may function as molecules in the biological processes underlying frailty. However, these studies have focused on structured exercise programs or cross-sectional PA-protein associations. Therefore, the effects of long-term PA on frailty-associated proteins remain unknown. Among 14,898 middle-aged adults, we emulated a target trial that assigned individuals to either (i) achieve and maintain the recommended PA level (≥150 minutes/week of moderate-to-vigorous physical activity [MVPA]) through 6 (±0.3) years of follow-up or (ii) follow a "natural course" strategy, where all individuals engage in various amounts of habitual MVPA. We estimated the effects of long-term adherence to recommended MVPA versus the natural course strategy on 45 previously identified frailty-associated proteins (log 2 transformed and standardized) at the end of the follow-up using inverse probability of weighting (IPW) and iterative conditional expectations (ICE). We found that long-term adherence to recommended MVPA improved the population levels of many frailty-associated proteins (ranged from 0.04 to 0.11 standard deviation); the greatest benefits were seen in proteins involved in the nervous system (e.g., voltage-dependent calcium channel subunit alpha-2/delta-3 [CACNA2D3], contactin-1 [CNTN1], neural cell adhesion molecule 1 [NCAM1], and transmembrane protein 132D [TMEM132D]) and inflammation (e.g., high-temperature requirement serine protease A1 [HTRA1] and C-reactive protein [CRP]). Our findings suggest long-term engagement in adequate habitual PA may reduce frailty risk through specific nervous systems and inflammatory proteins.

Relation of Adult-Onset Asthma to Coronary Heart Disease and Stroke

Evidence exists that increased levels of physical activity decrease the population burden of cardiovascular disease (CVD). Although risk factors for CVD, including plasma lipids and lipoproteins, have been associated with physical activity, studies including a sizeable number of minority participants are lacking. Our purpose was to interrogate the longitudinal effect of physical activity on plasma lipids and lipoproteins in the African American and white participants of the Atherosclerosis Risk in Communities (ARIC) Study. Nine years of follow-up data on 8,764 individuals aged 45-64 years at baseline were used in linear mixed-effects models to estimate the association between increases in baseline physical activity on mean change in HDL, LDL, total cholesterol, and triglyceride levels. Increases in the level of activity were associated with increases in HDL in all strata and decreases in triglycerides among white participants. Physical activity was associated with LDL in all women, while the association with total cholesterol was limited to African American women. This study is one of the few to investigate the effect of physical activity on lipids and lipoproteins in a race- and sex-specific manner. Overall our results highlight the importance of physical activity on plasma lipid profiles and provide evidence for novel differential associations.

This report was derived from a workshop on cardiovascular risk assessment sponsored by the National Heart, Lung, and Blood Institute, which addressed whether risk equations developed in the Framingham Heart Study (FHS) for predicting new-onset coronary heart disease (CHD) apply to diverse population groups. Preparation for the workshop included a reanalysis and comparison of prospective studies in several different populations in which risk factors were related to cardiovascular outcomes. Some studies included fatal and nonfatal CHD end points, whereas others contained only CHD mortality. Extensive collaboration provided as much uniformity as possible with respect to both risk factors and CHD end points. The FHS has led in defining the quantitative impact of risk factors.1 Many potential risk factors were measured and related to cardiovascular outcomes. Several risk factors proved to be strong, largely independent predictors of cardiovascular disease (CVD). These factors—advancing age, cigarette smoking, blood pressure (particularly systolic), cholesterol in total serum and HDL, and diabetes—served as the basis for the development of risk prediction equations.1 If FHS risk estimates are to be widely used, they must apply widely in the US population. To document their transportability, they must be compared with prospective studies in other populations. Although the FHS is the longest running prospective study, there are other major studies. The cardiovascular end points of these other studies have varied. Some include cardiovascular morbidity and mortality; others have only cardiovascular mortality. Among the end points, CHD is the most extensively reported; for this reason, CHD was the primary focus of the workshop. ### Multivariate Relative Risk Comparisons In preparation for the workshop, multivariate regression coefficients for each risk factor were compared in different populations with those of the FHS. Adjusted relative risk estimates make it possible to determine whether each independent risk factor confers a similar or different relative risk among different …

Introduction: Engagement in leisure-time physical activity (PA) levels recommended by the American Heart Association (AHA) is inversely associated with ischemic stroke risk. PA level can fluctuate over time but the association between PA fluctuations and ischemic stroke risk is unknown. The extent that ischemic stroke risk could be attenuated by increasing PA among those who are inactive could inform stroke prevention. Hypothesis: We hypothesize that participants who remained active or increased their PA levels will have lower ischemic stroke risk relative to those who were persistently inactive. Methods: We included 12,611participants of the Atherosclerosis Risk in Communities (ARIC) cohort study ages 45-64 at visit 1 (1987-1989) who did not have a history of stroke at visit 3 (1993-1995). Leisure-time PA was assessed using the modified Baecke questionnaire at visits 1 and 3 and categorized according to the AHA guidelines for PA (ideal, intermediate, or poor). All adjudicated definite and probable incident ischemic strokes between visit 3 and end of year 2013 were included. Cox-proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ischemic stroke by cross-categories of PA at visits 1 and 3 using those with poor PA at both visits as the referent group. We adjusted for age, sex, race/center, smoking status, and alcohol intake at visit 3. Results: During a median of 18.6 years of follow-up, 777 incident ischemic stroke events occurred. Compared with those with poor PA at visits 1 and 3, participants with ideal PA at both visits had the lowest ischemic stroke risk (HR=0.64, 0.51, 0.80). Those whose PA increased from poor to ideal also had significantly lower ischemic stroke risk (HR = 0.70, 0.53, 0.94). Conclusion: Sustained ideal PA was associated with the lowest ischemic stroke risk. Increasing PA between visit 1 and visit 3 was also associated with significantly lower ischemic stroke risk. Increasing PA may be an important component of stroke prevention.

Orthostatic hypotension (OH) results from a failure of neural and circulatory mechanisms to compensate for the reduction in venous return that normally occurs on assuming the upright posture. OH is defined as a fall in systolic blood pressure of ≥20 mm Hg or diastolic blood pressure of ≥10 mm Hg measured within 3 minutes of standing.1 OH can result from side effects of medications, intravascular volume loss, systemic diseases that involve autonomic nerves (eg, diabetes mellitus or amyloidosis), and, in rare cases, it can be the initial sign of a primary autonomic failure syndrome (multiple system atrophy, pure autonomic failure, and Parkinson’s disease). Severe OH can be a dramatic medical condition, with affected patients unable to stand but for few seconds before disabling symptoms of cerebral hypoperfusion and syncope ensue. Asymptomatic OH is a far more common condition, but one that is often unrecognized. It is a frequent finding in the elderly, with prevalence reported between 6% and 35% or more, depending on the age group and associated comorbidities.2,3 During the past 2 decades, evidence from cross-sectional and longitudinal epidemiological studies has identified OH as an independent risk factor for cardiovascular morbidity and all-cause mortality.4 In prospective studies, the presence of OH at baseline increased the risk of subsequent adverse outcomes, including stroke,5 coronary heart disease,6 and all-cause mortality.2,4,7,8 In this …

TV viewing and venous thromboembolism: Risk or red herring?

Serum magnesium and the incidence of coronary artery disease over a median 27 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study and a meta-analysis

Secular changes in rates of coronary heart disease, fatal coronary heart disease, and out-of-hospital fatal coronary heart disease

Background: Chronic inflammation is related to carcinogenesis. Many studies reported a positive association between plasma CRP - a non-specific marker of systemic inflammation - and colorectal cancer (CRC) risk. In the ARIC study, hazard ratio (HR) for CRC was 1.97 (95% CI,1.13; 3.43) for the highest versus lowest CRP quartile, although it is unclear if the association is causal. The associations of CRP with other cancer types are inconsistent. Our goals were to prospectively 1) examine associations of plasma CRP with other cancer types and total cancer and 2) examine associations of a genetic risk score based on single nucleotide polymorphisms (SNPs), affecting CRP levels, with cancer risk. Methods: The ARIC cohort aged 45-64 y at Visit 1 in 1987-89 (55% women, 28% African-American and 72% Caucasian) was followed until 2006. Among 8,657 Caucasians, we examined the incidence of total (n=1,929), CRC (n=205), breast (n=371), lung (n=274), and prostate (n=395) cancers in relation to a weighted genetic CRP risk score (CRPRS) composed of 20 SNPs located in/near CRP, APOC1, GCKR, HNF1A, IL6R and 15 other genes. These SNPs were associated with CRP levels in a previous meta-analysis of genome-wide association studies. The CRPRS was created as a sum of risk alleles for each person by multiplying each SNP by the beta coefficient from the meta-analysis. Plasma CRP was measured at Visit 4 (1996-98). We examined associations of plasma CRP with the risk of total (n=1,481), breast (n=235), lung (n=185), and prostate (n=352) cancers among 9,857 Caucasians and African-Americans, followed from Visit 4 until 2006. Cox proportional hazards models were used to estimate HRs of cancers in relation to plasma CRP and the genetic score. Results: CRPRS was positively associated with CRC risk HR =1.18 (1.03; 1.36) per one standard deviation of the score but not with total or any other cancer in a multivariate analysis. Additional adjustment for plasma CRP only slightly attenuated the association. The HRs were similar for colon and rectal cancer. After multivariate adjustment, plasma CRP was associated positively with the risk of breast and lung cancers: 2.40 (95%CI, 1.25; 4.61) (p-trend=0.004) and 1.90 (95%CI, 1.12; 3.22)(p-trend=0.03), respectively, for the highest versus lowest quartiles. The association for breast cancer did not markedly change after excluding subjects with < 3 years of follow-up or CRP>10mg/L, whereas for lung cancer both exclusions resulted in weaker associations. Conclusions: This study provides the first evidence of a significant association of CRP polymorphisms with CRC risk suggesting a role of CRP and inflammation in colorectal carcinogenesis. CRP polymorphisms may be linked with CRC risk through plasma CRP or other mechanisms. We also found that not only colorectal but also breast and lung cancers are positively associated with plasma CRP in the ARIC study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1028. doi:1538-7445.AM2012-1028

The long-term effect of physical activity on incidence of coronary heart disease: A 12-year follow-up study

ObjectiveIn the majority of studies, the effect of physical activity (PA) on cardiovascular disease (CVD) and mortality is estimated at a single time point. The impact of long-term PA is...

A Clinical Risk Score for Atrial Fibrillation in a Biracial Prospective Cohort (from the Atherosclerosis Risk In Communities [ARIC] Study)

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