Osteoporosis and Its Association With Cardiovascular Disease,Respiratory Disease,and Cancer: Findings From the UK Biobank Prospective Cohort Study

ObjectiveTo investigate sex-specific associations of osteoporosis with incidence of and mortality from cardiovascular disease (CVD), respiratory disease, and cancer as well as with all-cause mortality.MethodsIn total, 305,072 participants (53% [161,383] women) of UK Biobank were included in this study (2007-2010). Self-reported diagnosis of osteoporosis at baseline was the exposure of interest. The outcomes were CVD, respiratory disease, chronic obstructive pulmonary disease (COPD), all cancer, and prostate and breast cancer incidence and mortality and all-cause mortality. Associations between osteoporosis and outcomes were investigated using Cox proportional hazards models.ResultsIn men, osteoporosis was associated with a higher incident risk of all respiratory diseases (hazard ratio [HR], 1.26; 95% CI, 1.06 to 1.50) including COPD (HR, 1.82; 95% CI, 1.38 to 2.40). Men with osteoporosis also had a higher mortality risk from all causes (HR, 1.71; 95% CI, 1.38 to 2.11), CVD (HR, 1.68; 95% CI, 1.19 to 2.37), respiratory disease (HR, 2.35; 95% CI, 1.70 to 3.24), and COPD (HR, 3.64; 95% CI, 2.24 to 5.91). These associations persisted after adjustment for age, body mass index, and comorbidities. Women with osteoporosis had a higher risk of incident CVD (HR, 1.24; 95% CI, 1.97 to 1.44), respiratory disease (HR, 1.23; 95% CI, 1.13 to 1.33), and COPD (HR, 1.29; 95% CI, 1.10 to 1.52). Women with osteoporosis also had a higher mortality risk from respiratory disease (HR, 1.31; 95% CI, 1.00 to 1.72) and breast cancer (HR, 1.60; 95% CI, 1.14 to 2.26).ConclusionCompared with women, men with osteoporosis had a higher risk of all-cause mortality, mortality from respiratory diseases including COPD, and cancer incidence. Osteoporosis was strongly associated with respiratory disease and COPD in both sexes, even after full adjustment for covariates, although men with osteoporosis experienced a higher risk of adverse outcomes.     

Association of Changes in Physical Activity and Adiposity With Mortality and Incidence of Cardiovascular Disease: Longitudinal Findings From the UK Biobank

ObjectiveTo examine the association of changes in physical activity and adiposity with all-cause mortality and incident cardiovascular disease (CVD).MethodsPhysical activity, body mass index (BMI), body fat percentage, waist circumference, and waist to hip ratio changes were categorized on the basis of public health and clinical guidelines. Among 29,610 participants (mean ± SD follow-up, 5.1±2.1 years), 545 deaths and 2970 CVD events occurred. Participants were observed from baseline (March 13, 2006, to October 10, 2010) and follow-up (August 1, 2012 to November 9, 2018) assessment through March 31, 2021.ResultsCompared with stable-insufficient physical activity, increasing physical activity to meet guidelines at follow-up was associated with lower all-cause mortality (hazard ratio, 0.64 [0.49 to 0.85]) and CVD (0.83 [0.72 to 0.96]) risk. This risk was similar to that of those who achieved physical activity guidelines at both time points (all-cause mortality, 0.74 [0.60 to 0.92]; CVD, 0.88 [0.79 to 0.99]). For obese and overweight participants, decreasing BMI category was associated with a lower CVD risk (0.70 [0.47 to 1.04]) similar to the risk of those who had a healthy weight at both time points (0.85 [0.76 to 0.96]). In the joint analyses, the only combination that lowered all-cause mortality and CVD risk was physical activity increase and adiposity decrease over time (eg, CVD risk: BMI, 0.64 [0.42 to 0.96]; body fat percentage, 0.76 [0.55 to 0.97]; waist circumference, 0.66 [0.48 to 0.89]; waist to hip ratio, 0.78 [0.62 to 0.97]) compared with the reference group (stable physical activity and adiposity).ConclusionIncreases in physical activity to meet guidelines lowered all-cause mortality and CVD risk equal to that of those who continually met guidelines. The risk was effectively eliminated in those who had concurrent adiposity decrease.     

Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials

ObjectivesTo quantify the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on cardiovascular disease (CVD) prevention and the effect of dosage.MethodsThis study is designed as a random effects meta-analysis and meta-regression of randomized control trials with EPA/DHA supplementation. This is an update and expanded analysis of a previously published meta-analysis which covers all randomized control trials with EPA/DHA interventions and cardiovascular outcomes published before August 2019. The outcomes included are myocardial infarction (MI), coronary heart disease (CHD) events, CVD events (a composite of MI, angina, stroke, heart failure, peripheral arterial disease, sudden death, and non-scheduled cardiovascular surgical interventions), CHD mortality and fatal MI. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.ResultsA total of 40 studies with a combined 135,267 participants were included. Supplementation was associated with reduced risk of MI (relative risk [RR], 0.87; 95% CI, 0.80 to 0.96), high certainty number needed to treat (NNT) of 272; CHD events (RR, 0.90; 95% CI, 0.84 to 0.97), high certainty NNT of 192; fatal MI (RR, 0.65; 95% CI, 0.46 to 0.91]), moderate certainty NNT = 128; and CHD mortality (RR, 0.91; 95% CI, 0.85 to 0.98), low certainty NNT = 431, but not CVD events (RR, 0.95; 95% CI, 0.90 to 1.00). The effect is dose dependent for CVD events and MI.ConclusionCardiovascular disease remains the leading cause of death worldwide. Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect probably increases with dosage.     

Association of Proton Pump Inhibitors With Higher Risk of Cardiovascular Disease and Heart Failure

ObjectiveTo examine associations of cumulative exposure to proton pump inhibitors (PPIs) with total cardiovascular disease (CVD; composed of stroke, coronary heart disease, and heart failure [HF]) and HF alone in a cohort study of White and African American participants of the Atherosclerosis Risk in Communities (ARIC) study.MethodsUse of PPIs was assessed by pill bottle inspection at visit 1 (January 1, 1987 to 1989) and up to 10 additional times before baseline (visit 5; 2011 to 2013). We calculated cumulative exposure to PPIs as days of use from visit 1 to baseline. Participants (n=4346 free of total CVD at visit 5; mean age, 75 years) were observed for incident total CVD and HF events through December 31, 2016. We used Cox regression to measure associations of PPIs with total CVD and HF.ResultsAfter adjustment for potential confounding variables, participants with a cumulative exposure to PPIs of more than 5.1 years had a 2.02-fold higher risk of total CVD (95% CI, 1.50 to 2.72) and a 2.21-fold higher risk of HF (95% CI, 1.51 to 3.23) than nonusers.ConclusionLong-term PPI use was associated with twice the risk of total CVD and HF compared with nonusers. Our findings are in concordance with other research and suggest another reason to be cautious of PPI overuse.     

Fitness and Mortality Among Persons 70 Years and Older Across the Spectrum of Cardiovascular Disease Risk Factor Burden: The FIT Project

ObjectiveTo determine whether fitness could improve mortality risk stratification among older adults compared with cardiovascular disease (CVD) risk factors.MethodsWe examined 6509 patients 70 years of age and older without CVD from the Henry Ford ExercIse Testing Project (FIT Project) cohort. Patients performed a physician-referred treadmill stress test between 1991 and 2009. Traditional categorical CVD risk factors (hypertension, hyperlipidemia, diabetes, and smoking) were summed from 0 to 3 or more. Fitness was grouped as low, moderate, and high (<6, 6 to 9.9, and ≥10 metabolic equivalents of task). All-cause mortality was ascertained through US Social Security Death Master files. We calculated age-adjusted mortality rates, multivariable adjusted Cox proportional hazards, and Kaplan-Meier survival models.ResultsPatients had a mean age of 75±4 years, and 3385 (52%) were women; during a mean follow-up of 9.4 years, there were 2526 deaths. A higher fitness level (P<.001), not lower CVD risk factor burden (P=.31), was associated with longer survival. The age-adjusted mortality rate per 1000 person-years was 56.7 for patients with low fitness and 0 risk factors compared with 24.9 for high fitness and 3 or more risk factors. Among patients with 3 or more risk factors, the adjusted mortality hazard was 0.68 (95% CI, 0.61 to 0.76) for moderate and 0.51 (95% CI, 0.44 to 0.60) for high fitness compared with the least fit.ConclusionAmong persons aged 70 years and older, there was no significant difference in survival of patients with 0 vs 3 or more risk factors, but a higher fitness level identified older persons with good long-term survival regardless of CVD risk factor burden.     

Nonlinear Associations Between Cumulative Dietary Risk Factors and Cardiovascular Diseases,Cancer, and All-Cause Mortality: A Prospective Cohort Study From UK Biobank

ObjectiveTo develop a score from cumulative dietary risk factors and examine its nonlinear associations with cardiovascular disease (CVD) and cancer incidence and mortality, as well as all-cause mortality.Patients and MethodsThere were 422,702 participants from UK Biobank included in this prospective study. Cumulative dietary risk factors were represented using a score ranging from 0 (healthiest) to 9 (least healthy). This was derived from 9 food items based on current UK guidelines using baseline data. Associations between the cumulative score and health outcomes were investigated using nonlinear penalized cubic splines fitted in Cox proportional hazard models. Follow-up was conducted until June 2020 for mortality, and for incidence, up to June 2020 in England and March 2017 in Wales and Scotland.ResultsThe median follow-up period was 9.0 years for incidence outcomes and 9.3 years for mortality outcomes. Each 1-point increment in the cumulative dietary risk factors score was associated with higher risk for incidence and mortality of the outcomes studied. The highest risks were identified for mortality due to heart failure (8.0% higher), CVD, and ischemic heart disease (both 7.0% higher). In addition, a higher diet score accounted for 18.8% of all deaths, 4.47% of incident cases of CVD, 25.5% of CVD deaths, 7.7% of incident cancers, and 18.2% of all cancer deaths.ConclusionOur findings show that dietary risk factors contributed to a large proportion of CVD and cancer events, as well as deaths, among those who did not meet most dietary recommendations.     

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study

ObjectiveTo prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes.Patients and MethodsPatients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health–AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non–current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020.ResultsA total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses.ConclusionThe international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.     

Association Between Personal Activity Intelligence and Mortality: Population-Based China Kadoorie Biobank Study

ObjectiveTo prospectively investigate the association between personal activity intelligence (PAI) — a novel metabolic metric which translates heart rate during physical activity into a simple weekly score — and mortality in relatively healthy participants in China whose levels and patterns of physical activity in addition to other lifestyle factors are different from those in high-income countries.Patients and MethodsFrom the population-based China Kadoorie Biobank study, 443,792 healthy adults were recruited between June 2004 and July 2008. Participant’s weekly PAI score was estimated and divided into four groups (PAI scores of 0, ≤50, 51–99, or ≥100). Using Cox proportional hazard analyses, we calculated adjusted hazard ratios (AHRs) for cardiovascular disease (CVD) and all-cause mortality related to PAI scores.ResultsDuring a median follow-up of 8.2 (interquartile range, 7.3 to 9.1) years, there were 21,901 deaths, including 9466 CVD deaths. Compared with the inactive group (0 PAI score), a baseline weekly PAI score greater than or equal to 100 was associated with a lower risk of CVD mortality, an AHR of 0.87 (95% CI, 0.81 to 0.94) in men, and an AHR of 0.84 (95% CI, 0.78 to 0.92) in women, after adjusting for multiple confounders. Participants with a weekly PAI score greater than or equal to 100 also had a lower risk of all-cause mortality (AHR, 0.93; 95% CI, 0.89 to 0.97 in men, and AHR, 0.93; 95%, 0.88 to 0.98 in women). Moreover, this subgroup gained 2.7 (95% CI, 2.4 to 3.0) years of life, compared with the inactive cohort.ConclusionAmong relatively healthy Chinese adults, the PAI metric was inversely associated with CVD and all-cause mortality, highlighting the generalizability of the score in different races, ethnicities, and socioeconomic strata.     

Plant-Based Diets and All-cause and Cardiovascular Mortality in a Nationwide Cohort in Spain: The ENRICA Study

ObjectiveTo investigate the associations of a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) with all-cause and cardiovascular disease (CVD) mortality in Spanish adults.Patients and MethodsWe analyzed data from 11,825 individuals 18 years of age or older, representative of the Spanish population, recruited between 2008 and 2010 and followed-up to 2020. Food consumption was collected at baseline using a validated dietary history, which served to calculate two plant-based diet indices based on 18 major food groups (range, 18-90 points). For (1) hPDI only the consumption of healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea/coffee) received positive scores; whereas for (2) uPDI, only the consumption of less healthy plant foods (fruit juices, sugar-sweetened beverages, refined grains, potatoes, and sweets/desserts) received positive scores. Multivariable-adjusted Cox models were used to estimate HRs and their 95% CIs.ResultsAfter a median follow-up of 10.9 and 9.8 years, 699 all-cause and 157 CVD deaths were ascertained, respectively. Each 10-point increase in hPDI was associated with 14% lower risk of all-cause death (HR, 0.86; 95% CI, 0.74 to 0.99), and 37% lower risk of CVD death (HR, 0.63; 95% CI, 0.46 to 0.85). No significant associations were found for uPDI.ConclusionHigher adherence to an hPDI diet, but not to a uPDI, was associated with lower all-cause and CVD mortality. This suggests that the quality of the plant food consumed is paramount to achieve diet-related benefits in mortality.Trial registrationclinicaltrials.gov Identifier: NCT02804672     

Role of Physical Activity in Lowering Risk of End-Stage Renal Disease

ObjectiveTo investigate the association between the amount and intensity of leisure-time physical activity (LTPA) and the risk of end-stage renal disease (ESRD).MethodsThe study examined a cohort of 543,667 participants aged 20 years and older who participated in a health screening program from January 1, 1996, through December 31, 2017. We identified 2520 individuals undergoing dialysis or who had a kidney transplant by linking participants’ encrypted personal identification with the registry for ESRD with a median follow-up of 13 years. We classified participants into 5 categories measured by metabolic equivalent of tasks. Within each category, we analyzed the effect of moderate- and vigorous-intensity LTPA in reducing risk of ESRD. We used a Cox proportional hazards model to calculate hazard ratios (HRs).ResultsWe observed a dose-response relationship between LTPA and the risk of ESRD. The fully active group had a 12% lower hazard of ESRD compared with the no reported LTPA group (HR, 0.88; 95% CI, 0.80 to 0.98) adjusting for covariates including baseline estimated glomerular filtration rate and proteinuria. Within the same category of LTPA, vigorous-intensity exercise carried a 35% lower HR for ESRD compared with moderate-intensity exercise (HR, 0.65; 95% CI, 0.52 to 0.81). The effect was observed stronger among men, younger participants, and participants with diabetes or hyperlipidemia.ConclusionSustained LTPA (≥ 150 minutes per week), particularly with vigorous intensity, significantly lowered the ESRD risk, even among individuals with comorbidities such as diabetes or hyperlipidemia. This finding suggested that patients with no reported LTPA with cardiovascular risks should engage in more LTPA to lower their risk of ESRD.     

Physical Activity and Mortality Across Levels of Adiposity: A Prospective Cohort Study From the UK Biobank

ObjectiveTo examine the combined and stratified associations of physical activity and adiposity measures, modelled as body mass index (BMI), abdominal adiposity (waist circumference), and body fat percentage (BF) with all-cause mortality.Patients and MethodsUsing the UK Biobank cohort, we extracted quintiles of self-reported weekly physical activity. Categories of measured BMI, waist circumference, and BF were generated. Joint associations between physical activity-adiposity categories and mortality were examined using Cox proportional hazards models adjusted for demographic, behavioral, and clinical covariates. Physical activity-mortality associations were also examined within adiposity strata. Participants were followed from baseline (2006 to 2010) through January 31, 2018.ResultsA total of 295,917 participants (median follow-up, 8.9 years, during which 6684 deaths occurred) were included. High physical activity was associated with lower risk of premature mortality in all strata of adiposity except for those with BMI ≥35 kg/m². Highest risk (HR, 1.54; 95% CI; 1.33 to 1.79) was observed in individuals with low physical activity and high BF as compared with the high physical activity–low BF referent. High physical activity attenuated the risk of high adiposity when using BF (HR, 1.24; 95% CI; 1.04 to 1.49), but the association was weaker with BMI (HR, 1.45; 95% CI; 1.21 to 1.73). Physical activity also attenuated the association between mortality and high waist circumference.ConclusionLow physical activity and adiposity were both associated with a higher risk of premature mortality, but high physical activity attenuated the increased risk with adiposity irrespective of adiposity metric, except in those with a BMI ≥35 kg/m².     

Cardiometabolic Health Outcomes Associated With Discordant Visceral and Liver Fat Phenotypes: Insights From the Dallas Heart Study and UK Biobank

ObjectiveTo evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts.Patients and MethodsParticipants in the Dallas Heart Study underwent baseline imaging from January 1, 2000, through December 31, 2002, and were followed for incident cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) through 2013. Associations between VAT-LF groups (low-low, high-low, low-high, and high-high) and outcomes were assessed using multivariable-adjusted regression and were replicated in the independent UK Biobank.ResultsThe Dallas Heart Study included 2064 participants (mean ± SD age, 44±9 years; 54% female; 47% black). High VAT–high LF and high VAT–low LF were associated with prevalent atherosclerosis, whereas low VAT–high LF was not. Of 1731 participants without CVD/T2DM, 128 (7.4%) developed CVD and 95 (5.5%) T2DM over a median of 12 years. High VAT–high LF and high VAT–low LF were associated with increased risk of CVD (hazard ratios [HRs], 2.0 [95% CI, 1.3 to 3.2] and 2.4 [95% CI, 1.4 to 4.1], respectively) and T2DM (odds ratios [ORs], 7.8 [95% CI, 3.8 to 15.8] and 3.3 [95% CI, 1.4 to 7.8], respectively), whereas low VAT–high LF was associated with T2DM (OR, 2.7 [95% CI, 1.1 to 6.7]). In the UK Biobank (N=22,354; April 2014-May 2020), only high VAT–low LF remained associated with CVD after multivariable adjustment for age and body mass index (HR, 1.5 [95% CI, 1.2 to 1.9]).ConclusionAlthough VAT and LF are each associated with cardiometabolic risk, these observations demonstrate the importance of separating their cardiometabolic implications when there is presence or absence of either or both in an individual.     

The Lifestyle-Related Cardiovascular Risk Is Modified by Sleep Patterns

ObjectiveTo prospectively assess whether sleep patterns modified lifestyle-associated cardiovascular disease (CVD) risk.Patients and MethodsThis study included 393,690 participants without CVD at baseline measurements between March 13, 2006, and October 1, 2010, from UK Biobank. A lifestyle score was calculated on the basis of the 4 lifestyle factors (smoking, alcohol consumption, physical activity, and diet), and sleep patterns were constructed based on sleep duration, chronotype, insomnia, snoring, and daytime dozing.ResultsDuring a median follow-up of 8.93 years, we observed 10,218 incident CVD events, including 6595 myocardial infarctions (MIs) and 3906 strokes. We found that sleep patterns significantly modified the relations of the lifestyle score with incident CVD (P for interaction =.007) and MI (P for interaction =.004). Among participants with a poor sleep pattern, unfavorable lifestyle (per score increase) was associated with 25% (95% CI, 13% to 39%) and 29% (95% CI, 13% to 47%) increased risks for CVD and MI, while among participants with a healthy sleep pattern, unfavorable lifestyle was associated with 18% (95% CI, 15% to 21%) and 17% (95% CI, 13% to 21%) increased risks for CVD and MI.ConclusionOur results indicate that adherence to a healthy sleep pattern may attenuate the CVD risk associated with an unfavorable lifestyle.     

U-Shaped Association Between Duration of Sports Activities and Mortality: Copenhagen City Heart Study

ObjectiveTo investigate the association between the duration of weekly leisure-time sports activity and all-cause mortality.MethodsAs part of the prospective Copenhagen City Heart Study, 8697 healthy adults completed a comprehensive questionnaire about leisure-time sports activities. Duration (minutes per week) of leisure-time sports activities was recorded for tennis, badminton, soccer, handball, cycling, swimming, jogging, calisthenics, health club activities, weightlifting, and other sports. The primary end point was all-cause mortality, and the median follow-up was 25.6 years. The association between duration of leisure-time sports activities and all-cause mortality was studied using multivariable Cox proportional hazards regression analysis.ResultsCompared with the reference group of 2.6 to 4.5 hours of weekly leisure-time sports activities, we found an increased risk for all-cause mortality for those with 0 hours (hazard ratio [HR], 1.51; 95% CI, 1.29 to 1.76), for those with 0.1 to 2.5 hours (HR, 1.24; 95% CI, 1.05 to 1.46), and for those with more than 10 hours (HR, 1.18; 95% CI, 1.00 to 1.39) of weekly leisure-time sports activities. These relationships were generally consistent with additional adjustments for potential confounders among subgroups of age, sex, education, smoking, alcohol intake, and body mass index, when the first 5 years of follow-up were excluded, and for cardiovascular disease mortality.ConclusionWe observed a U-shaped association between weekly duration of leisure sports activities and cardiovascular and all-cause mortality, with lowest risk for those participating in 2.6 to 4.5 weekly hours, being consistent across subgroups. Participation in sport activities should be promoted, but the potential risk of very high weekly hours of sport participation should be considered for inclusion in guidelines and recommendations.     

Lower Extremity Arterial Disease as a Predictor of Incident Atrial Fibrillation and Cardiovascular Events

ObjectiveTo evaluate the relationship between peripheral arterial disease (PAD) and incident atrial fibrillation (AF) and its clinical and pathophysiologic implications on ischemic stroke and all-cause mortality.Patients and MethodsWe identified all adult patients in the Mayo Clinic Health System without a previous diagnosis of AF undergoing ankle-brachial index (ABI) testing for any indication from January 1, 1996, to June 30, 2018. Retrospective extraction of ABI data and baseline echocardiographic data was performed. The primary outcome of interest was incident AF. The secondary outcomes of interest were incident ischemic stroke and all-cause mortality.ResultsA total of 33,734 patients were included in the study. After adjusting for demographic and comorbidity variables, compared with patients who had normal ABI (1.0 to 1.39), there was an increased risk of incident AF in patients with low ABI (<1.0) (adjusted hazard ratio, 1.14; 95% CI, 1.06 to 1.22) and elevated ABI (≥1.4) (adjusted hazard ratio, 1.18; 95% CI, 1.06 to 1.31). The risk was greater in patients with increasing severity of PAD. Patients with abnormal ABIs had an increased risk of ischemic stroke and all-cause mortality. We found that patients with PAD and incident AF have certain baseline echocardiographic abnormalities.ConclusionIn this large cohort of ambulatory patients undergoing ABI measurement, patients with PAD were at increased risk for incident AF, ischemic stroke, and mortality. In these high-risk patients with abnormal ABI, particularly severe PAD and cardiac structural abnormalities, routine monitoring for AF and management of cardiovascular risk factors may be warranted.     

Relative Predictive Value of Circulating Immune Markers in US Adults Without Cardiovascular Disease: Implications for Risk Reclassification

ObjectiveTo investigate the relative predictive value of circulating immune cell markers for cardiovascular mortality in ambulatory adults without cardiovascular disease.MethodsWe analyzed data of participants enrolled in the National Health and Nutrition Examination Survey from January 1, 1999, to December 31, 2010, with the total leukocyte count within a normal range (4000-11,000 cells/μL [to convert to cells ×10⁹/L, multiply by 0.001]) and without cardiovascular disease. The relative predictive value of circulating immune cell markers measured at enrollment—including total leukocyte count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio, and C-reactive protein—for cardiovascular mortality was evaluated. The marker with the best predictive value was added to the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to estimate net risk reclassification indices for 10-year cardiovascular mortality.ResultsAmong 21,599 participants eligible for this analysis, the median age was 47 years (interquartile range, 34-63 years); 10,651 (49.2%) participants were women, and 10,713 (49.5%) were self-reported non-Hispanic white. During a median follow-up of 9.6 years (interquartile range, 6.8-13.1 years), there were 627 cardiovascular deaths. MLR had the best predictive value for cardiovascular mortality. The addition of elevated MLR (≥0.3) to the 10-year ASCVD risk score improved the classification by 2.7%±1.4% (P=.04). Elevated MLR had better predictive value than C-reactive protein and several components of the 10-year ASCVD risk score.ConclusionAmong ambulatory US adults without preexisting cardiovascular disease, we found that MLR had the best predictive value for cardiovascular mortality among circulating immune markers. The addition of MLR to the 10-year risk score significantly improved the risk classification of participants.     

Association of Cardiovascular Disease Risk Factors With Sociodemographic Characteristics and Health Beliefs Among a Community-Based Sample of African American Adults in Minnesota

ObjectiveTo assess cardiovascular disease (CVD) and CVD risk factors and their association with sociodemographic characteristics and health beliefs among African American (AA) adults in Minnesota.MethodsA cross-sectional analysis was conducted of a community-based sample of AA adults enrolled in the Minnesota Heart Health Program Ask About Aspirin study from May 2019 to September 2019. Sociodemographic characteristics, health beliefs, and self-reported CVD and CVD risk factors were collected. Prevalence ratio (PR) estimates were calculated using Poisson regression modeling to assess the association between participants’ characteristics and age- and sex-adjusted CVD risk factors.ResultsThe sample included 644 individuals (64% [412] women) with a mean age of 61 years. Risk factors for CVD were common: hypertension (67% [434]), hyperlipidemia (47% [301]), diabetes (34% [219]), and current cigarette smoking (25% [163]); 19% (119) had CVD. Those with greater perceived CVD risk had a higher likelihood of prevalent hyperlipidemia (PR, 1.34; 95% CI, 1.14 to 1.57), diabetes (PR, 1.61; 95% CI, 1.30 to 1.98), and CVD (PR 1.61; 95% CI, 1.16 to 2.23) compared with those with lower perceived risk. Trust in health care provider was high (83% [535]) but was not associated with CVD or CVD risk factors.ConclusionIn this community sample of AAs in Minnesota, CVD risk factors were high, as was trust in health care providers. Those with greater CVD risk perceptions had higher CVD prevalence. Consideration of sociodemographic and psychosocial influences on CVD and CVD risk factors could inform development of effective cardiovascular health promotion interventions in the AA Minnesota community.     

Repeat Coronary Bypass Surgery or Percutaneous Coronary Intervention After Previous Surgical Revascularization

ObjectiveTo assess long-term survival with repeat coronary artery bypass grafting (RCABG) or percutaneous coronary intervention (PCI) in patients with previous CABG.MethodsFrom January 1, 2000, through December 31, 2013, 1612 Mayo Clinic patients underwent RCABG (n=215) or PCI (n=1397) after previous CABG. The RCABG cohort was grouped by use of saphenous vein grafts only (n=75), or with additional arterial grafts (n=140); the PCI cohort by, bare metal stents (BMS; n=628), or drug-eluting stents (DES; n=769), and by the treated target into native coronary artery (n=943), bypass grafts only (n=338), or both (n=116). Multivariable regression and propensity score analysis (n=280 matched patients) were used.ResultsIn multivariable analysis, the 30-day mortality was increased in RCABG versus PCI patients (hazard ratio [HR], 5.32; 95%CI, 2.34-12.08; P<.001), but overall survival after 30 days improved with RCABG (HR, 0.72; 95% CI, 0.55-0.94; P=.01). Internal mammary arteries were used in 61% (129 of 215) of previous CABG patients and improved survival (HR, 0.82; 95% CI, 0.69-0.98; P=.03). Patients treated with drug-eluting stent had better 10-year survival (HR, 0.74; 95% CI, 0.59-0.91; P=.001) than those with bare metal stent alone. In matched patients, RCABG had improved late survival over PCI: 48% vs 33% (HR, 0.57; 95% CI, 0.35-0.91; P=.02). Compared with RCABG, patients with PCI involving bypass grafts (n=60) had increased late mortality (HR, 1.62; 95% CI, 1.10-2.37; P=.01), whereas those having PCI of native coronary arteries (n=80) did not (HR, 1.09; 95% CI, 0.75-1.59; P=.65).ConclusionRCABG is associated with improved long-term survival after previous CABG, especially compared with PCI involving bypass grafts.     

Tricuspid Regurgitation Impact on Outcomes (TRIO): A Simple Clinical Risk Score

ObjectiveTo determine which clinical variables infer the highest risk for mortality in patients with notable tricuspid regurgitation (TR) and to develop a clinical assessment tool (the Tricuspid Regurgitation Impact on Outcomes [TRIO] score).Patients and MethodsA single-center retrospective cohort of 13,608 patients with undifferentiated moderate to severe TR at the time of index echocardiography between January 1, 2005, and December 31, 2016, was included. Baseline demographic and clinical data were obtained. Patients were randomly assigned to a training (N=10,205) and a validation (N=3403) cohort. Median follow-up was 6.5 years (interquartile range, 0.8 to 11.0 years). Variables associated with mortality were identified by Cox proportional hazards methods. A geographically distinct cohort of 7138 patients was used for further validation. The primary end point was all-cause mortality over 10 years.ResultsThe 5-year probability of death was 53% for moderate TR, 63% for moderate-severe TR (hazard ratio [HR], 1.24 [95% CI, 1.17 to 1.31]; P<.001 vs moderate), and 71% for severe TR (HR, 1.55 [95% CI, 1.47 to 1.64]; P<.001 vs moderate). Factors associated with all-cause mortality on multivariate analysis included age 70 years or older, male sex, creatinine level greater than 2 mg/dL, congestive heart failure, chronic lung disease, aspartate aminotransferase level of 40 U/L or greater, heart rate of 90 beats/min or greater, and severe TR. Variables were assigned 1 or 2 points (HR, >1.5) and added to compute the TRIO score. The score was associated with all-cause mortality (C statistic = 0.67) and was able to separate patients into risk categories. Findings were similar in the second, independent and geographically distinct cohort.ConclusionThe TRIO score is a simple clinical tool for risk assessment in patients with notable TR. Future prospective studies to validate its use are warranted.     

Peripheral Artery Disease and Subsequent Risk of Infectious Disease in Older Individuals: The ARIC Study

ObjectiveTo quantify the association of peripheral artery disease (PAD) with infection risk because PAD has been understudied despite recognition of atherosclerotic cardiovascular disease as a risk factor for infection.MethodsAmong 5082 participants of the Atherosclerosis Risk in Communities study (aged 71 to 90 years during 2011-2013), we assessed the association of PAD status, based on clinical history and ankle-brachial index (ABI), with infection-related hospitalization (through December 2019) using multivariable Cox regression. We also cross-classified participants by PAD and coronary heart disease (CHD)/stroke status at baseline, with implications for polyvascular disease.ResultsDuring the median follow-up of 6.5 years, there were 1677 infection-related hospitalizations. Peripheral artery disease (clinical history or ABI ≤0.90) was independently associated with the risk of overall infection (adjusted hazard ratio [HR], 1.66 [95% CI, 1.42 to 1.94] vs ABI of 1.11 to 1.20), as was borderline low ABI of 0.91 to 1.00 (adjusted HR, 1.75 [95% CI, 1.47 to 2.07]). Results were consistent across major types of infection (ie, cellulitis, bloodstream infection, pneumonia, and urinary tract infection). For overall infection, PAD plus CHD/stroke had the highest HR of hospitalized infection (1.9), and PAD alone and CHD/stroke alone showed similar HRs of 1.6. For subtypes of infection, PAD alone had the highest HR of approximately 2 for bloodstream infection; PAD alone and PAD plus CHD/stroke had a similar risk of urinary tract infection with HR of approximately 1.7.ConclusionPeripheral artery disease and borderline low ABI were robustly associated with infection-related hospitalization of older adults. The contribution of PAD to infection risk was comparable to that of CHD/stroke, warranting clinical attention to PAD for the prevention of infectious diseases.