Synergistic and Non-synergistic Associations for Cigarette Smoking and Non-tobacco Risk Factors for Cardiovascular Disease Incidence in the Atherosclerosis Risk In Communities (ARIC) Study

Cigarette smoking, various metabolic and lipid-related factors and hypertension are well-recognized cardiovascular disease (CVD) risk factors. Since smoking affects many of these factors, use of a single imprecise smoking metric, e.g., ever or never smoked, may allow residual confounding and explain inconsistencies in current assessments of interactions. Using a comprehensive model in pack-years and cigarettes/day for the complex smoking-related relative risk (RR) of CVD to reduce residual confounding, we evaluated interactions with non-tobacco risk factors, including additive (non-synergistic) and multiplicative (synergistic) forms. Data were from the prospective Atherosclerosis Risk in Communities (ARIC) Study from four areas of the U.S. recruited in 1987-89 with follow-up through 2008. Analyses included 14,127 participants, 207,693 person-years and 2,857 CVD events. Analyses revealed distinct interactions with smoking: including statistical consistency with additive (body mass index, waist to hip ratio, diabetes mellitus, glucose, insulin, high density lipoproteins [HDL] and HDL(2)); and multiplicative (hypertension, total cholesterol, low density lipoproteins, apolipoprotein B, total cholesterol to HDL ratio and HDL(3)) associations, as well as indeterminate (apolipoprotein A-I and triglycerides) associations. The forms of the interactions were revealing but require confirmation. Improved understanding of joint associations may help clarify the public health burden of smoking for CVD, links between etiologic factors and biological mechanisms, and the consequences of joint exposures, whereby synergistic associations highlight joint effects and non-synergistic associations suggest distinct contributions. Joint associations for cigarette smoking and non-tobacco risk factors were distinct, revealing synergistic/multiplicative (hypertension, TC, LDL, apoB, TC/HDL, HDL(3)), non-synergistic/additive (BMI, WHR, DM, glucose, insulin, HDL, HDL(2)) and indeterminate (apoA-I and TRIG) associations. If confirmed, these results may help better define the public health burden of smoking on CVD risk and identify links between etiologic factors and biologic mechanisms, where synergistic associations highlight joint impacts and non-synergistic associations suggest distinct contributions from each factor

Dietary intake and peripheral arterial disease incidence in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Peripheral arterial disease (PAD) is a costly source of morbidity and mortality among older persons in the United States. Dietary intake plays a role in the development of atherosclerotic cardiovascular disease; however, few studies have examined the relation of food intake or dietary patterns with PAD

Inpatient and Outpatient Infection as a Trigger of Cardiovascular Disease: The ARIC Study

Background Acute infections are known cardiovascular disease (CVD) triggers, but little is known regarding how CVD risk varies following inpatient versus outpatient infections. We hypothesized that in‐ and outpatient infections are associated with CVD risk and that the association is stronger for inpatient infections. Methods and Results Coronary heart disease (CHD) and ischemic stroke cases were identified and adjudicated in the ARIC (Atherosclerosis Risk in Communities Study). Hospital discharge diagnosis codes and Medicare claims data were used to identify infections diagnosed in in‐ and outpatient settings. A case‐crossover design and conditional logistic regression were used to compare in‐ and outpatient infections among CHD and ischemic stroke cases (14, 30, 42, and 90 days before the event) with corresponding control periods 1 and 2 years previously. A total of 1312 incident CHD cases and 727 incident stroke cases were analyzed. Inpatient infections (14‐day odds ratio [OR]=12.83 [5.74, 28.68], 30‐day OR=8.39 [4.92, 14.31], 42‐day OR=6.24 [4.02, 9.67], and 90‐day OR=4.48 [3.18, 6.33]) and outpatient infections (14‐day OR=3.29 [2.50, 4.32], 30‐day OR=2.69 [2.14, 3.37], 42‐day OR=2.45 [1.97, 3.05], and 90‐day OR=1.99 [1.64, 2.42]) were more common in all CHD case periods compared with control periods and inpatient infection was a stronger CHD trigger for all time periods (P Conclusions In‐ and outpatient infections are associated with CVD risk. Patients with an inpatient infection may be at particularly elevated CVD risk and should be considered potential candidates for CVD prophylaxis

Inpatient versus outpatient acute venous thromboembolism management: Trends and postacute healthcare utilization from 2011 to 2018

Background - Acute outpatient management of venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is perceived to be as safe as inpatient management in some settings. How widely this strategy is used is not well documented. Methods and Results - Using MarketScan administrative claims databases for years 2011 through 2018, we identified patients with International Classification of Diseases (ICD) codes indicating incident VTE and trends in the use of acute outpatient management. We also evaluated healthcare utilization and hospitalized bleeding events in the 6 months following the incident VTE event. A total of 200 346 patients with VTE were included, of whom 50% had evidence of PE. Acute outpatient management was used for 18% of those with PE and 57% of those with DVT only, and for both DVT and PE its use increased from 2011 to 2018. Outpatient management was less prevalent among patients with cancer, higher Charlson comorbidity index scores, and whose primary treatment was warfarin as compared with a direct oral anticoagulant. Healthcare utilization in the 6 months following the incident VTE event was generally lower among patients managed acutely as outpatients, regardless of initial presentation. Acute outpatient management was associated with lower hazard ratios of incident bleeding risk for both patients who initially presented with PE (0.71 [95% CI, 0.61, 0.82]) and DVT only (0.59 [95% CI, 0.54, 0.64]). Conclusions - Outpatient management of VTE is increasing. In the present analysis, it was associated with lower subsequent healthcare utilization and fewer bleeding events. However, this may be because healthier patients were managed on an outpatient basis

Autoimmune disease and risk of postpartum venous thromboembolism

Background - The risk of pregnancy-related mortality in the United States has nearly doubled since 1990, with venous thromboembolism (VTE) accounting for approximately 10% of these deaths. Objectives - The objective of this study was to assess whether preexisting autoimmune disease is a risk factor for postpartum VTE. Methods - Using the MarketScan Commercial and Medicare Supplemental administrative databases, a retrospective cohort study analyzed whether postpartum persons with autoimmune disease had a higher risk of postpartum VTE incidence than postpartum persons without autoimmune disease. Using International Classification of Diseases codes, we identified 757,303 individuals of childbearing age who had a valid delivery date with at least 12 weeks of follow-up. Results - Individuals were, on average, 30.7 years old (SD, 5.4), and 3.7% (N = 27,997 of 757,303) of them had evidence of preexisting autoimmune disease. In covariate-adjusted models, postpartum persons with preexisting autoimmune disease had higher rates of postpartum VTE than postpartum persons without autoimmune disease (hazard ratio [HR], 1.33; 95% CI, 1.07-1.64). When analyzed by individual autoimmune disease, those with systemic lupus erythematosus (HR, 2.49; 95% CI, 1.47-4.21) and Crohn’s disease (HR, 2.49; 95% CI, 1.34-4.64) were at an elevated risk of postpartum VTE compared with those without autoimmune disease. Conclusion - Autoimmune disease was associated with a higher rate of postpartum VTE, with evidence that the association was most pronounced among individuals with systemic lupus erythematosus and Crohn’s disease. These findings suggest that postpartum persons of childbearing age with autoimmune disease may require more monitoring and prophylactic care after delivery to prevent potentially fatal VTE events

Community Prevalence of Ideal Cardiovascular Health, by the AHA Definition, and Relation to Cardiovascular Disease Incidence

To estimate the prevalence of ideal cardiovascular health and its relation to incident cardiovascular disease (CVD)

Life’s Simple 7’s Cardiovascular Health Metrics are Associated with Hispanic/Latino Neurocognitive Function: HCHS/SOL Results

Hispanics/Latinos are purportedly at increased risk for neurocognitive decline and dementias. Without dementia cures, low-cost, well-tolerated public health means for mitigating neurocognitive decline are needed

Serum magnesium, phosphorus, and calcium are associated with risk of incident heart failure: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Heart failure (HF) is a major source of morbidity and mortality, particularly among the elderly. Magnesium, phosphorus, and calcium are micronutrients traditionally viewed in relation to bone health or chronic kidney disease. However, they also may be associated with risk of cardiovascular disease through a broad range of physiologic roles

Ideal Cardiovascular Health During Adult Life and Cardiovascular Structure and Function Among the Elderly.

BACKGROUND: A higher American Heart Association cardiovascular health score (CVHS) predicts a lower incidence of cardiovascular disease (CVD). However, the relationship of CVHS attainment through midlife to late life with CVD prevalence and cardiovascular structure and function in late life is not well described. METHODS AND RESULTS: The following 6 ideal cardiovascular health metrics were assessed in the Atherosclerosis Risk in Communities (ARIC) study participants at 5 examination visits between 1987 and 2013: nonsmoking, body mass index <25 kg/m(2), untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, fasting blood glucose <100 mg/dL, and ideal physical activity. Attainment over time was assessed as the percentage of maximum possible CVHS metrics achieved at visits 1 through 5, the slope of change in CVHS per decade of follow-up, and CVHS trajectory through follow-up. At visit 5, participant groups were characterized with respect to CVD prevalence (n=6520) and echocardiographic measures of cardiac structure and function (n=5903 free of CVD). CVHS was low at baseline and declined with age. Both greater CVHS attainment and improvement in CVHS during follow-up were associated with a lower prevalence of CVD and better left ventricular structure and systolic and diastolic function at visit 5. CONCLUSIONS: Greater attainment of, and improvements in, ideal cardiovascular health through midlife to late life are associated with lower CVD prevalence and better cardiovascular structure and function when elderly. These findings highlight the importance of consistent primordial and primary prevention efforts throughout midlife to late life as a potential intervention to decrease the burden of CVD among the elderly