Yasuhiko Kubota

Physical activity and lifetime risk of cardiovascular disease and cancer

Purpose Although the World Health Organization has recommended moderate- to vigorous-intensity physical activity (MVPA) to prevent cardiovascular disease (CVD) and some cancers, there are no estimates of lifetime risk of these noncommunicable diseases according to PA levels. We aimed to estimate the lifetime risk of CVD and cancers according to PA levels. Methods We followed 5807 men and 7252 women in the United States, 45–64 yr old, initially free of CVD and cancer from 1987 through 2012, and used a life table approach to estimate lifetime risks of CVD (coronary heart disease, heart failure, and stroke) and total cancer according to PA levels: poor (0 min·wk−1 of MVPA), intermediate (1–74 min·wk−1 of VPA or 1–149 min·wk−1 of MVPA), or recommended (≥75 min·wk−1 of VPA or ≥150 min·wk−1 of MVPA). Results During the 246,886 person-years of follow-up, we documented 4065 CVD and 3509 cancer events and 2062 non-CVD and 2326 noncancer deaths. In men, the lifetime risks of CVD from 45 through 85 yr were 52.7% (95% confidence interval = 49.4–55.5) for poor PA and 45.7% (42.7–48.3) for recommended PA. In women, the respective lifetime risks of CVD were 42.4% (39.5–44.9) and 30.5% (27.5–33.1). Lifetime risks of total cancer were 40.1% (36.9–42.7) for poor PA and 42.6% (39.7–45.2) for recommended activity in men and 31.4% (28.7–33.8) and 30.4% (27.7–32.9), respectively, in women. Conclusions Compared with a poor PA level, the PA recommended by the World Health Organization was associated with lower lifetime risk of CVD, but not total cancer, in both men and women.

Association of Educational Attainment With Lifetime Risk of Cardiovascular Disease: The Atherosclerosis Risk in Communities Study

Importance Estimates of lifetime risk may help raise awareness of the extent to which educational inequalities are associated with risk of cardiovascular disease (CVD). Objective To estimate lifetime risks of CVD according to categories of educational attainment. Design, Setting, and Participants Participants were followed from 1987 through December 31, 2013. All CVD events (coronary heart disease, heart failure, and stroke) were confirmed by physician review and International Classification of Diseases codes. A total of 13 948 whites and African Americans who were 45 to 64 years old and free of CVD at baseline were included from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburbs of Minneapolis, Minnesota). The data analysis was performed from June 7 to August 31, 2016. Exposures Educational attainment. Main Outcomes and Measures We used a life table approach to estimate lifetime risks of CVD from age 45 through 85 years according to educational attainment. We adjusted for competing risks of death from underlying causes other than CVD. Results The sample of 13 948 participants was 56% female and 27% African American. During 269 210 person-years of follow-up, we documented 4512 CVD events and 2401 non-CVD deaths. Educational attainment displayed an inverse dose-response relation with cumulative risk of CVD, which became evident in middle age, with the most striking gap between those not completing vs completing high school. In men, lifetime risks of CVD were 59.0% (95% CI, 54.0%-64.1%) for grade school, 52.5% (95% CI, 47.7%-56.8%) for high school education without graduation, 50.9% (95% CI, 47.3%-53.9%) for high school graduation, 47.2% (95% CI, 41.5%-52.5%) for vocational school, 46.4% (95% CI, 42.8%-49.6%) for college with or without graduation, and 42.2% (95% CI, 36.6%-47.0%) for graduate/professional school; in women, 50.8% (95% CI, 45.7%-55.8%), 49.3% (95% CI, 45.1%-53.1%), 36.3% (95% CI, 33.4%-39.1%), 32.2% (95% CI, 26.0%-37.3%), 32.8% (95% CI, 29.1%-35.9%), and 28.0% (95% CI, 21.9%-33.3%), respectively. Educational attainment was inversely associated with CVD even within categories of family income, income change, occupation, or parental educational level. Conclusions and Relevance More than 1 in 2 individuals with less than high school education had a lifetime CVD event. Educational attainment was inversely associated with the lifetime risk of CVD, regardless of other important socioeconomic characteristics. Our findings emphasize the need for further efforts to reduce CVD inequalities related to educational disparities.

Lung function, respiratory symptoms and venous thromboembolism risk: the Atherosclerosis Risk in Communities Study

Essentials The association of lung function with venous thromboembolism (VTE) is unclear. Chronic obstructive pulmonary disease (COPD) patterns were associated with a higher risk of VTE. Symptoms were also associated with a higher risk of VTE, but a restrictive pattern was not. COPD may increase the risk of VTE and respiratory symptoms may be a novel risk marker for VTE.

Serum uric acid, gout, and venous thromboembolism: The atherosclerosis risk in communities study

INTRODUCTION Inflammatory diseases increase risk of venous thromboembolism (VTE). Whether gout, the most common rheumatologic inflammatory arthritis, or its cause, elevated serum uric acid (SUA), is associated with VTE incidence is unknown. MATERIALS AND METHODS The Atherosclerosis Risk in Communities Study measured SUA in 14126 participants aged 45-64, without a history of VTE or gout and not using anticoagulants/gout medications, and obtained information on incident gout between 1987 and 1998 from 10247. We followed them for VTE occurrence from 1987 to 2011. Hazard ratios (HRs) of VTE were estimated using Cox proportional hazards models. RESULTS We documented 632 incident cases of VTE (236 unprovoked and 396 provoked). Age, sex, and race-adjusted HRs for total VTE were 1, 1.40, 1.43, 1.91, 1.71, and 3.25 (P for trend<0.001) across levels of SUA (range mg/dL: ≤4.9, 5.0-5.9, 6.0-6.9, 7.0-7.5, 7.6-8.7, and ≥8.8). After adjustment for other VTE risk factors, those in the highest level of SUA had HRs [95% confidence interval] of 2.13 (1.47-3.07) for total VTE, 2.07 (1.17-3.67) for unprovoked VTE and 2.16 (1.33-3.50) for provoked VTE. Those with incident gout had a nonsignificantly increased risk of total VTE [HR (95% CI): 1.33 (0.95-1.86)]. CONCLUSIONS Elevated SUA was associated with an increased risk of VTE, suggesting that SUA might be a novel risk factor or marker for VTE. Further studies are needed to assess the association between gout and VTE.

TV viewing and incident venous thromboembolism: the Atherosclerotic Risk in Communities Study

TV viewing is associated with risk of arterial vascular diseases, but has not been evaluated in relation to venous thromboembolism (VTE) risk in Western populations. In 1987–1989, the Atherosclerosis Risk in Communities Study obtained information on the frequency of TV viewing in participants aged 45–64 and followed them prospectively. In individuals free of prebaseline VTE (n = 15, 158), we used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to frequency of TV viewing (“Never or seldom”, “Sometimes”, “Often” or “Very often”). During the 299,767 person-years of follow-up, we identified 691 VTE events. In a multivariable-adjusted model, the frequency of TV viewing showed a positive dose–response relation with VTE incidence (P for trend = 0.036), in which “very often” viewing TV carried 1.71 (95% CI 1.26–2.32) times the risk of VTE compared with “never or seldom” viewing TV. This association to some degree was mediated by obesity (25% mediation, 95% CI 10.7–27.5). Even among individuals who met a recommended level of physical activity, viewing TV “very often” carried 1.80 (1.04–3.09) times the risk of VTE, compared to viewing TV “never or seldom”. Greater frequency of TV viewing was independently associated with increased risk of VTE, partially mediated by obesity. Achieving a recommended physical activity level did not eliminate the increased VTE risk associated with frequent TV viewing. Avoiding frequent TV viewing as well as increasing physical activity and controlling body weight might be beneficial for VTE prevention.

β-Thromboglobulin and incident cardiovascular disease risk: The Atherosclerosis Risk in Communities study

INTRODUCTION Although it has been suggested that increased concentrations of activated platelet biomarkers are associated with increased risk of incident cardiovascular disease (CVD) in the general population, evidence for this association is still controversial. Thus, we tested the hypothesis that activated platelets, measured by higher concentrations of β-thromboglobulin, are associated with increased risk of incident CVD (coronary heart disease, heart failure ischemic stroke, and atrial fibrillation). MATERIALS AND METHODS We prospectively followed a cohort random sample of the Atherosclerosis Risk in Communities (ARIC) cohort, aged 45-64years, and free of CVD at baseline who had previous measurements of plasma β-thromboglobulin. We identified incident CVD from 1987 through 2013, and used a weighted Cox proportional hazard models to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs). RESULTS During the 14,387person-years of follow-up for the 746 participants, we identified 140 coronary heart diseases, 123 heart failures, 54 ischemic strokes, and 126 atrial fibrillations. The age-, sex-, and race-adjusted model showed no association between plasma β-thromboglobulin and CVD, regardless of subtypes. After further adjustment for other CVD risk factors, including antiplatelet agent use, β-thromboglobulin remained unassociated with CVD risk. CONCLUSIONS In the prospective population-based ARIC cohort, β-thromboglobulin was not associated with CVD risk. Our results do not support the hypothesis that a blood marker of higher platelet activity reflects increased future risk of CVD in the general population.

Diabetes-Related Factors and Abdominal Aortic Aneurysm (AAA) Events: The Atherosclerotic Risk in Communities Study

Diabetes-Related Factors and Abdominal Aortic Aneurysm (AAA) Events: The Atherosclerotic Risk in Communities Study Kubota Y, Folsom AR, Pankow JS, Wagenknecht LE, Tang W. Ann Epidemiol 2018;28:102-6. Study design: Longitudinal study of patients entered at baseline between 1987 and 1989 in the Atherosclerosis Risk in Communities (ARIC) study from four U.S. communities in Mississippi, Maryland, Minnesota, and North Carolina. Key findings: The study followed 13,736 men and women aged 45 to 64 for abdominal aortic aneurysm (AAA) occurrence through 2011. Although fasting serum glucose and plasma leptin were inversely associated with AAA risk, patients with metabolic syndrome had increased occurrence of AAA. Conclusion: Diabetes, fasting glucose, and plasma leptin were inversely associated with risk of AAA, but metabolic syndrome was associated with increased risk of AAA. Commentary: Although atherosclerosis, male sex, hypertension, dyslipidemia, and smoking have been identified as risk factors for AAA, diabetes has been shown to be inversely associated with AAA occurrence (this is a common vascular board question!). Hyperglycemia is associated with increased collagen synthesis, elevated formation of glycation end products, and decreased matrix metalloproteinases, all of which cause increased arterial stiffness by promoting cross-links between proteins such as elastin and collagen in the vessel wall and thus decreased risk of developing AAA. Metabolic syndrome is a precursor to diabetes in many people but nonetheless was associated with increased risk of AAA due to nonglucose metabolic syndrome components. This is the first study to show a positive association between metabolic syndrome and AAA.

Homocysteine and Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities Study and the Multi-Ethnic Study of Atherosclerosis

BACKGROUND Although many studies have investigated the association of blood homocysteine with major cardiovascular diseases such as coronary heart disease and stroke, research on its association with atrial fibrillation (AF) is scarce. METHODS We analysed data from Atherosclerosis Risk in Communities (ARIC) Study (n=492, age 45-64 years) and Multi-Ethnic Study of Atherosclerosis (MESA) (n=6,641, age 45-84 years). RESULTS During the 10,106 and 67,613 person-years of follow-up, we identified 85 and 351 AF events in ARIC and MESA, respectively. An age-, sex-, and race-adjusted model showed dose-response relations between plasma homocysteine concentrations and AF incidence in both ARIC and MESA. Further adjustments for other AF risk factors did not change the associations. In the fully adjusted model, a meta-analysis of both studies showed a significant association between homocysteine and AF [hazard ratio (95% confidence interval) per 1 unit increment in log2(homocysteine), 1.27 (1.01-1.61)]. Individuals with higher levels of all three B vitamins (vitamin B6 and B12, and folate) had a lower risk of AF, but those associations were not statistically significant. In the full ARIC cohort [n=12,686 (2079 AF events)], there was no association between the C677T methylenetetrahydrofolate reductase (MTHFR) mutation and AF. CONCLUSIONS In the prospective population-based ARIC and MESA cohorts, elevated homocysteine was modestly associated with an increased risk of incident AF, but the C677T MTHFR mutation was not associated with AF risk, suggesting that homocysteine may be a novel risk marker for AF rather than a causal risk factor.

Diabetes-related factors and abdominal aortic aneurysm events: the Atherosclerotic Risk in Communities Study

PURPOSE To test the hypothesis that diabetes-related factors (metabolic syndrome [MetS], glucose, insulin, and leptin) are inversely associated with abdominal aortic aneurysm (AAA) risk. METHODS We followed 13,736 participants, aged 45-64 years, without prior AAA surgery at baseline (1987-1989), for AAA occurrence through 2011. Hazard ratios (HRs) and their 95% confidence intervals (CIs) of AAA were calculated using Cox regression. RESULTS During 275,054 person-years of follow-up, we identified 518 AAA events. Fasting serum glucose was associated inversely with AAA risk (HR [95% CI] per one unit increment in log2(glucose), 0.54 [0.36-0.80]), but fasting insulin was not associated with AAA. Plasma leptin was also associated inversely with AAA occurrence (HR [95% CI] per one unit increment in log2(leptin), 0.83 [0.71-0.98]). Compared with individuals without MetS, those with MetS had increased risk of AAA (HR [95% CI], 1.24 [1.04-1.48]). Among individuals with or without diabetes, the HRs increased monotonically with a greater number of non-glucose MetS components. CONCLUSIONS Diabetes, fasting glucose, and plasma leptin were inversely associated with risk of AAA. In contrast, the MetS was associated with increased risk of AAA, due to the influence of the non-glucose MetS components.