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Background: Inflammation and coagulation may contribute to the increased risk for atherosclerotic cardiovascular disease (ASCVD) associated with high lipoprotein(a). The association of lipoprotein(a) with ASCVD is stronger in individuals with high versus low high-sensitivity C-reactive protein (hs-CRP), a marker of inflammation., Objectives: Determine the association of lipoprotein(a) with incident ASCVD by levels of coagulation Factor VIII controlling for hs-CRP., Methods: We analyzed data from 6,495 men and women 45 to 84 years of age in the Multi-Ethnic Study of Atherosclerosis (MESA) without prevalent ASCVD at baseline (2000-2002). Lipoprotein(a) mass concentration, Factor VIII coagulant activity, and hs-CRP were measured at baseline and categorized as high or low (≥75 th or <75 th percentile of the distribution). Participants were followed for incident coronary heart disease (CHD) and ischemic stroke through 2015., Results: Over a median follow-up of 13.9 years, there were 390 CHD and 247 ischemic stroke events. The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) (≥40.1 versus <40.1 mg/dL) including adjustment for hs-CRP among participants with low and high Factor VIII was 1.07 (0.80-1.44) and 2.00 (1.33-3.01), respectively (p-value for interaction 0.016). The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) including adjustment for Factor VIII was 1.16 (0.87-1.54) and 2.00 (1.29-3.09) among participants with low and high hs-CRP, respectively (p-value for interaction 0.042). Lp(a) was not associated with ischemic stroke regardless of Factor VIII or hs-CRP levels., Conclusion: High lipoprotein(a) is a risk factor for CHD in adults with high levels of hemostatic or inflammatory markers., (Copyright © 2023. Published by Elsevier Inc.)

Background: Individual inflammation biomarkers are associated with incident coronary heart disease (CHD) events. However, there is limited research on whether the risk for incident CHD is progressively higher with a higher number of inflammation biomarkers in abnormal levels., Methods: We used data from 15,758 Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants aged ≥45 years without a history of CHD at baseline in 2003-2007. Abnormal levels of baseline high-sensitivity C-reactive protein, leukocyte count and serum albumin were defined as ≥3.8 mg/L (3rd tertile), ≥6.3 x 10 9 cells/L (3rd tertile), and <4.0 g/dL (1st tertile), respectively. The outcome was a composite of incident myocardial infarction or CHD death., Results: Overall, 38.9% (n = 6,123) had 0, 36.6% (n = 5,774) had 1, 19.8% (n = 3,113) had 2 and 4.7% (n = 748) had 3 biomarkers of inflammation in abnormal levels. Over a median follow-up of 11.4 years, 954 (6.1%) participants had incident CHD. The rate of incident CHD per 1000 person-years for individuals with 0, 1, 2, and 3 biomarkers of inflammation in abnormal levels was 4.4 (95% confidence interval [CI]: 3.9-5.0), 6.3 (95% CI: 5.6-6.9), 8.8 (95% CI: 7.8-9.9), and 10.6 (95% CI: 8.1-13.1), respectively. Multi-variable adjusted hazard ratios for incident CHD associated with 1, 2 and 3 versus no inflammation biomarker in abnormal levels were 1.26 (95% CI: 1.07-1.49), 1.72 (95% CI: 1.43-2.07), and 1.84 (95% CI: 1.37-2.47), respectively (P-trend < .001)., Conclusions: The number of inflammation markers in abnormal levels was associated with increased risk of incident CHD after multi-variable adjustment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background It is unclear whether lipoprotein(a) is associated with coronary heart disease (CHD) and ischemic stroke events in White and Black adults with atherosclerotic cardiovascular disease (ASCVD). Methods and Results We conducted a case-cohort analysis, including Black and White REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants ≥45 years of age with prevalent ASCVD (ie, CHD or stroke) at baseline between 2003 and 2007. Baseline lipoprotein(a) molar concentration was measured in participants with ASCVD who experienced a CHD event by December 2017 (n=1166) or an ischemic stroke by September 2019 (n=492) and in a random subcohort of participants with prevalent ASCVD (n=1948). The hazard ratio (HR) for CHD events per 1 SD (1.5 units) higher log-transformed lipoprotein(a) was 1.26 (95% CI, 1.02-1.56) among Black participants and 1.16 (95% CI, 1.02-1.31) among White participants ( P value comparing HRs, 0.485). The HR for CHD events per 1 SD higher log-lipoprotein(a) within subgroups with hs-CRP (high-sensitivity C-reactive protein) ≥2 and <2 mg/L was 1.31 (95% CI, 0.99-1.73) and 1.23 (95% CI, 0.85-1.80), respectively ( P value comparing HRs, 0.836), among Black participants, and 1.07 (95% CI, 0.91-1.27) and 1.36 (95% CI, 1.10-1.70), respectively ( P value comparing HRs, 0.088), among White participants. There was no evidence that the association between lipoprotein(a) and CHD events differed by statin use. There was no evidence of an association between lipoprotein(a) and ischemic stroke events among Black or White participants. Conclusions Higher lipoprotein(a) levels were associated with an increased risk for CHD events in Black and White adults with ASCVD.

Objective: To determine the association of serum urate (SU) levels with sudden cardiac death and incident coronary heart disease (CHD), separately, among adults without a history of CHD., Methods: We conducted a case-cohort analysis of Black and White participants aged ≥ 45 years enrolled in the REason for Geographic And Racial Differences in Stroke (REGARDS) study without a history of CHD at baseline between 2003 and 2007. Participants were followed for sudden cardiac death or incident CHD (i.e., myocardial infarction [MI] or death from CHD excluding sudden cardiac death) through December 31, 2013. Baseline SU was measured in a random sample of participants (n = 840) and among participants who experienced sudden cardiac death (n = 235) or incident CHD (n = 851) during follow-up., Results: Participants with higher SU levels were older and more likely to be male or Black. The crude HR (95% CI) per 1 mg/dL higher SU level was 1.26 (1.14-1.40) for sudden cardiac death and 1.17 (1.09-1.26) for incident CHD. After adjustment for age, sex, race, and cardiovascular risk factors, the HR (95% CI) per 1 mg/dL higher SU level was 1.19 (1.03-1.37) for sudden cardiac death and 1.05 (0.96-1.15) for incident CHD. HRs for sudden cardiac death were numerically higher among participants aged 45-64 vs ≥ 65 years, without vs with diabetes, and among those of White vs Black race, although P values for effect modification were all ≥ 0.05., Conclusion: Higher SU levels were associated with an increased risk for sudden cardiac death but not with incident CHD., (Copyright © 2021 by the Journal of Rheumatology.)

Background: Migraine has been associated with cardiovascular disease (CVD) events among middle-aged adults. The objective of this study was to determine the risk for ischemic stroke and coronary heart disease (CHD) events among older adults with versus without migraine., Methods: This retrospective cohort study was conducted using data from US adults ≥66 years of age with Medicare health insurance between 2008 and 2017. After stratification by history of CVD, patients with a history of migraine were matched 1:4 to those without a history of migraine, based on calendar year, age, and sex. Patients were followed through December 31, 2017 for ischemic stroke and CHD events including myocardial infarction or coronary revascularization. All analyses were done separately for patients with and without a history of CVD., Results: Among patients without a history of CVD (n = 109,950 including n = 21,990 with migraine and n = 87,960 without migraine), 1789 had an ischemic stroke and 3552 had a CHD event. The adjusted hazard ratio (HR) among patients with versus without migraine was 1.20 (95% confidence interval [95%CI], 1.07-1.35) for ischemic stroke and 1.02 (95%CI, 0.93-1.11) for CHD events. Compared to patients without migraine, those with migraine who were taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.43 [95%CI, 1.20-1.69]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.79 [95%CI, 0.67-0.93]). Among patients with a history of CVD (n = 79,515 including n = 15,903 with migraine and n = 63,612 without migraine), 2960 had an ischemic stroke and 7981 had a CHD event. The adjusted HRs (95%CI) for ischemic stroke and CHD events associated with migraine were 1.27 (1.17-1.39) and 0.99 (0.93-1.05), respectively. Patients with migraine taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.21 [95%CI, 1.07-1.36]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.83 [95%CI, 0.72-0.95]), each versus those without migraine., Conclusions: Older adults with migraine are at increased risk for ischemic stroke. The risk for ischemic stroke among older adults with migraine may differ by migraine medication classes., (© 2021. The Author(s).)

Background: Rates for recurrent coronary heart disease (CHD) events have declined in the United States. However, few studies have assessed whether this decline has been similar among women and men., Methods: Data were used from 770 408 US women and 700 477 US men <65 years of age with commercial health insurance through MarketScan and ≥66 years of age with government health insurance through Medicare who had a myocardial infarction (MI) hospitalization between 2008 and 2017. Women and men were followed up for recurrent MI, recurrent CHD events (ie, recurrent MI or coronary revascularization), heart failure hospitalization, and all-cause mortality (Medicare only) in the 365 days after MI., Results: From 2008 to 2017, age-standardized recurrent MI rates per 1000 person-years decreased from 89.2 to 72.3 in women and from 94.2 to 81.3 in men (multivariable-adjusted P interaction by sex <0.001). Recurrent CHD event rates decreased from 166.3 to 133.3 in women and from 198.1 to 176.8 in men ( P interaction <0.001). Heart failure hospitalization rates decreased from 177.4 to 158.1 in women and from 162.9 to 156.1 in men ( P interaction=0.001). All-cause mortality rates decreased from 403.2 to 389.5 in women and from 436.1 to 417.9 in men ( P interaction=0.82). In 2017, the multivariable-adjusted rate ratios comparing women with men were 0.90 (95% CI, 0.86-0.93) for recurrent MI, 0.80 (95% CI, 0.78-0.82) for recurrent CHD events, 0.99 (95% CI, 0.96-1.01) for heart failure hospitalization, and 0.82 (95% CI, 0.80-0.83) for all-cause mortality., Conclusions: Rates of recurrent MI, recurrent CHD events, heart failure hospitalization, and mortality in the first year after an MI declined considerably between 2008 and 2017 in both men and women, with proportionally greater reductions for women than men. However, rates remain very high, and rates of recurrent MI, recurrent CHD events, and death continue to be higher among men than women.

Background: Highly fragmented ambulatory care (i.e., care spread across many providers without a dominant provider) has been associated with excess tests, procedures, emergency department visits, and hospitalizations. Whether fragmented care is associated with worse health outcomes, or whether any association varies with health status, is unclear., Objective: To determine whether fragmented care is associated with the risk of incident coronary heart disease (CHD) events, overall and stratified by self-rated general health., Design and Participants: We conducted a secondary analysis of the nationwide prospective Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study (2003-2016). We included participants who were ≥ 65 years old, had linked Medicare fee-for-service claims, and had no history of CHD (N = 10,556)., Main Measures: We measured fragmentation with the reversed Bice-Boxerman Index. We used Cox proportional hazards models to determine the association between fragmentation as a time-varying exposure and adjudicated incident CHD events in the 3 months following each exposure period., Key Results: The mean age was 70 years; 57% were women, and 34% were African-American. Over 11.8 years of follow-up, 569 participants had CHD events. Overall, the adjusted hazard ratio (HR) for the association between high fragmentation and incident CHD events was 1.14 (95% confidence interval (CI) 0.92, 1.39). Among those with very good or good self-rated health, high fragmentation was associated with an increased hazard of CHD events (adjusted HR 1.35; 95% CI 1.06, 1.73; p = 0.01). Among those with fair or poor self-rated health, high fragmentation was associated with a trend toward a decreased hazard of CHD events (adjusted HR 0.54; 95% CI 0.29, 1.01; p = 0.052). There was no association among those with excellent self-rated health., Conclusion: High fragmentation was associated with an increased independent risk of incident CHD events among those with very good or good self-rated health.

Background: Women have lower age-specific rates of incident coronary heart disease (CHD) than men. It is unclear whether women remain at lower risk for CHD events versus men following a myocardial infarction (MI)., Objectives: This study assessed sex differences in recurrent MI, recurrent CHD events, and mortality among patients with MI and compared these associations with sex differences in a control group without a history of CHD., Methods: This study analyzed data for 171,897 women and 167,993 men age 21 years or older with health insurance in the United States who had a MI hospitalization in 2015 or 2016. Patients with a MI were frequency matched by age and calendar year to 687,588 women and 671,972 men without CHD. Beneficiaries were followed until December 2017 for MI, CHD (i.e., MI or coronary revascularization), and in Medicare for all-cause mortality., Results: Age-standardized rates of MI per 1,000 person-years were 4.5 in women and 5.7 in men without CHD (hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.62 to 0.67) and 60.2 in women and 59.8 in men with MI (HR: 0.94; 95% CI: 0.92 to 0.96). CHD rates in women versus men were 6.3 versus 10.7 among those without CHD (HR: 0.53; 95% CI: 0.51 to 0.54) and 84.5 versus 99.3 among those with MI (HR: 0.87; 95% CI: 0.85 to 0.89). All-cause mortality rates in women versus men were 63.7 versus 59.0 among those without CHD (HR: 0.72; 95% CI: 0.71 to 0.73) and 311.6 versus 284.5 among those with MI (HR: 0.90; 95% CI: 0.89 to 0.92)., Conclusions: The lower risk for MI, CHD, and all-cause mortality in women versus men is considerably attenuated following a MI., (Copyright © 2020. Published by Elsevier Inc.)

Background: High-intensity statins, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and antiplatelet agents (ie, intensive medical management) reduce coronary heart disease (CHD) risk after myocardial infarction (MI)., Objective: The objective of the study was to determine the risk of CHD events or death despite receiving intensive medical management after MI., Methods: We studied 16,853 United States adults with health insurance in the MarketScan and Medicare databases who underwent percutaneous coronary intervention while hospitalized for MI between January 1, 2014 and June 30, 2015 and received intensive medical management within 30 days after hospital discharge. MI, CHD, and all-cause mortality rates from 30 days after hospital discharge through December 31, 2015 were compared with 67,412 individuals in each of three groups: (1) the general MarketScan and Medicare populations, (2) with diabetes, and (3) with a CHD history., Results: Among beneficiaries intensively medically managed after their MI, recurrent MI, CHD events, and all-cause mortality rates were 47.1, 72.0, and 57.5 per 1000 person-years, respectively. The multivariable-adjusted hazard ratio (95% CI) comparing intensively medically managed beneficiaries after MI to the general population, those with diabetes, and those with a history of CHD were 8.54 (7.52-9.70), 7.40 (6.61-8.28), and 5.45 (4.92-6.05), respectively, for recurrent MI; 7.82 (7.07-8.64), 6.27 (5.74-6.86), and 4.45 (4.10-4.82), respectively, for CHD events; and 1.15 (1.05-1.25), 1.05 (0.97-1.14), and 1.06 (0.97-1.15), respectively, for all-cause mortality., Conclusion: Substantial residual risk for MI and CHD events remains despite intensive medical management after MI., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline provides updated recommendations for antihypertensive medication initiation and intensification., Objectives: Determine the risk for cardiovascular disease (CVD) events among adults recommended and not recommended antihypertensive medication initiation or intensification by the 2017 ACC/AHA BP guideline., Methods: The authors analyzed data for black and white REGARDS (REasons for Geographic And Racial Differences in Stroke) study participants (age ≥45 years). Systolic BP (SBP) and diastolic BP (DBP) were measured twice at baseline (2003 to 2007) and averaged. Participants not taking (n = 14,039) and taking (n = 15,179) antihypertensive medication were categorized according to their recommendations for antihypertensive medication initiation and intensification by the 2017 ACC/AHA guideline. Overall, 4,094 CVD events (stroke, coronary heart disease, and heart failure) occurred by December 31, 2014., Results: Among participants not taking antihypertensive medication, 34.4% were recommended pharmacological antihypertensive treatment initiation. The CVD event rate per 1,000 person-years among participants recommended antihypertensive medication initiation with SBP/DBP ≥140/90 mm Hg was 22.7 (95% confidence interval [CI]: 20.3 to 25.0). Among participants with SBP/DBP 130 to 139/80 to 89 mm Hg, the CVD event rate was 20.5 (95% CI: 18.5 to 22.6) and 3.4 (95% CI: 2.4 to 4.4) for those recommended and not recommended antihypertensive medication initiation, respectively. Among participants taking antihypertensive medication, 62.8% were recommended treatment intensification. The CVD event rate per 1,000 person-years among participants recommended treatment intensification was 33.6 (95% CI: 31.5 to 35.6) and 22.4 (95% CI: 20.8 to 23.9) for those with SBP/DBP ≥140/90 mm Hg and 130 to 139/80 to 89 mm Hg, respectively., Conclusions: Implementing the 2017 ACC/AHA guideline would direct antihypertensive medication initiation and intensification to adults with high CVD risk., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Blacks have higher coronary heart disease (CHD) mortality compared with whites. However, a previous study suggests that nonfatal CHD risk may be lower for black versus white men., Methods: We compared fatal and nonfatal CHD incidence and CHD case-fatality among blacks and whites in the Atherosclerosis Risk in Communities study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS) by sex. Participants 45 to 64 years of age in ARIC (men=6479, women=8488) and REGARDS (men=5296, women=7822), and ≥65 years of age in CHS (men=1836, women=2790) and REGARDS (men=3381, women=4112), all without a history of CHD, were analyzed. Fatal and nonfatal CHD incidence was assessed from baseline (ARIC=1987-1989, CHS=1989-1990, REGARDS=2003-2007) through up to 11 years of follow-up., Results: Age-adjusted hazard ratios comparing black versus white men 45 to 64 years of age in ARIC and REGARDS were 2.09 (95% confidence interval, 1.42-3.06) and 2.11 (1.32-3.38), respectively, for fatal CHD, and 0.82 (0.64-1.05) and 0.94 (0.69-1.28), respectively, for nonfatal CHD. After adjustment for social determinants of health and cardiovascular risk factors, hazard ratios in ARIC and REGARDS were 1.19 (95% confidence interval, 0.74-1.92) and 1.09 (0.62-1.93), respectively, for fatal CHD, and 0.64 (0.47-0.86) and 0.67 (0.48-0.95), respectively, for nonfatal CHD. Similar patterns were present among men ≥65 years of age in CHS and REGARDS. Among women 45 to 64 years of age in ARIC and REGARDS, age-adjusted hazard ratios comparing blacks versus whites were 2.61 (95% confidence interval, 1.57-4.34) and 1.79 (1.06-3.03), respectively, for fatal CHD, and 1.47 (1.13-1.91) and 1.29 (0.91-1.83), respectively, for nonfatal CHD. After multivariable adjustment, hazard ratios in ARIC and REGARDS were 0.67 (95% confidence interval, 0.36-1.24) and 1.00 (0.54-1.85), respectively, for fatal CHD, and 0.70 (0.51-0.97) and 0.70 (0.46-1.06), respectively, for nonfatal CHD. Racial differences in CHD incidence were attenuated among older women. CHD case fatality was higher among black versus white men and women, and the difference remained similar after multivariable adjustment., Conclusions: After accounting for social determinants of health and risk factors, black men and women have similar risk for fatal CHD compared with white men and women, respectively. However, the risk for nonfatal CHD is consistently lower for black versus white men and women., (© 2017 American Heart Association, Inc.)

Background: The atherosclerosis cardiovascular disease (ASCVD) Pooled Cohort risk equations have shown different calibration across US populations with varied levels of social deprivation., Methods and Results: We analyzed the calibration and discrimination of the Pooled Cohort risk equations by social deprivation status among 9066 REGARDS (REasons for Geographic And Racial Differences in Stroke) study participants not taking statins for whom ASCVD risk may lead to statin initiation. Patients were aged 45 to 79 years, had no ASCVD or diabetes mellitus, and had a low-density lipoprotein cholesterol level 70 to 189 mg/dL. Social deprivation was defined using 3 indicators: annual household income <$25 000, less than a high school education, and living without a partner. At baseline in 2003-2007, 54.6%, 27.4%, and 18.0% of participants had 0, 1, and 2 or 3 indicators showing deprivation, respectively. From baseline through December 2012, 457 participants developed ASCVD (nonfatal/fatal stroke, myocardial infarction, or coronary heart disease death). Predicted and observed ASCVD incidence per 1000 person-years were 8.02 and 6.23 (95% CI, 5.31-7.31), respectively, among participants with 0 indicators of deprivation (Hosmer-Lemeshow P =0.01); 8.05 and 6.61 (95% CI, 5.29-8.24), respectively, with 1 indicator ( P =0.09); and 9.83 and 11.40 (95% CI, 9.23-14.05), respectively, with 2 or 3 indicators ( P =0.12). The C-index (95% CI) was 0.72 (0.69-0.75), 0.73 (0.69-0.78), and 0.70 (0.65-0.75) among participants with 0, 1, and 2 or 3 indicators of deprivation, respectively. The net reclassification improvement after adding deprivation data to the Pooled Cohort risk equations was modest (0.12; 95% CI, 0.03-0.21)., Conclusions: The Pooled Cohort risk equations have good calibration among individuals with social deprivation but overestimate ASCVD risk among those with less social deprivation., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: In SPRINT (Systolic Blood Pressure Intervention Trial), a systolic blood pressure (SBP) goal of <120 mm Hg resulted in lower cardiovascular disease (CVD) risk compared with an SBP goal of <140 mm Hg., Objectives: The purpose of this study was to estimate the prevalence, number, and characteristics of U.S. adults meeting SPRINT eligibility criteria and determine the broader population to whom SPRINT could be generalized., Methods: We conducted a cross-sectional, population-based study using data from the National Health and Nutrition Examination Survey, 2007 to 2012. The SPRINT inclusion criteria were age ≥50 years, SBP 130 to 180 mm Hg depending on the number of antihypertensive medication classes being taken, and high CVD risk (history of coronary heart disease, estimated glomerular filtration rate of 20 to 59 ml/min/1.73 m(2), 10-year CVD risk ≥15%, or age ≥75 years). Exclusion criteria were diabetes, history of stroke, >1 g in 24 h of proteinuria daily, heart failure, estimated glomerular filtration rate <20 ml/min/1.73 m(2), or receiving dialysis. Treated hypertension was defined by self-reported use of medication to lower blood pressure with ≥1 class of antihypertensive medication identified through a pill bottle review., Results: Overall, 7.6% (95% confidence interval [CI]: 7.0% to 8.3%) or 16.8 million (95% CI: 15.7 to 17.8 million) U.S. adults, and 16.7% (95% CI: 15.2% to 18.3%) or 8.2 million (95% CI: 7.6 to 8.8 million) adults with treated hypertension met the SPRINT eligibility criteria. Among both the overall U.S. population and adults with treated hypertension, the percentage meeting SPRINT eligibility criteria increased with older age, was higher among males than females, and was higher among non-Hispanic whites compared with non-Hispanic blacks or Hispanics. Of U.S. adults eligible for SPRINT, 51.0% (95% CI: 47.8% to 54.1%) or 8.6 million (95% CI: 8.0 to 9.1 million) were not treated for hypertension., Conclusions: A substantial percentage of U.S. adults meet the eligibility criteria for SPRINT., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction. Methods: We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70–189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs. Results: We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%. Conclusions: These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment. [ABSTRACT FROM AUTHOR]

Background: Highly fragmented ambulatory care (i.e., care spread across many providers without a dominant provider) has been associated with excess tests, procedures, emergency department visits, and hospitalizations. Whether fragmented care is associated with worse health outcomes, or whether any association varies with health status, is unclear.Objective: To determine whether fragmented care is associated with the risk of incident coronary heart disease (CHD) events, overall and stratified by self-rated general health.Design and Participants: We conducted a secondary analysis of the nationwide prospective Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study (2003-2016). We included participants who were ≥ 65 years old, had linked Medicare fee-for-service claims, and had no history of CHD (N = 10,556).Main Measures: We measured fragmentation with the reversed Bice-Boxerman Index. We used Cox proportional hazards models to determine the association between fragmentation as a time-varying exposure and adjudicated incident CHD events in the 3 months following each exposure period.Key Results: The mean age was 70 years; 57% were women, and 34% were African-American. Over 11.8 years of follow-up, 569 participants had CHD events. Overall, the adjusted hazard ratio (HR) for the association between high fragmentation and incident CHD events was 1.14 (95% confidence interval (CI) 0.92, 1.39). Among those with very good or good self-rated health, high fragmentation was associated with an increased hazard of CHD events (adjusted HR 1.35; 95% CI 1.06, 1.73; p = 0.01). Among those with fair or poor self-rated health, high fragmentation was associated with a trend toward a decreased hazard of CHD events (adjusted HR 0.54; 95% CI 0.29, 1.01; p = 0.052). There was no association among those with excellent self-rated health.Conclusion: High fragmentation was associated with an increased independent risk of incident CHD events among those with very good or good self-rated health. [ABSTRACT FROM AUTHOR]

Background: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline includes recommendations for intensive lipid-lowering therapy in patients at very high risk for atherosclerotic cardiovascular disease (ASCVD) events.Objectives: This study sought to estimate event rates among adults with a history of ASCVD who met and did not meet the definition of very high risk in the 2018 AHA/ACC cholesterol guideline.Methods: Data from U.S. adults with health insurance in the MarketScan database who had a history of ASCVD on January 1, 2016 (n = 27,775) were analyzed. Very high risk for ASCVD events was defined as a history of ≥2 major ASCVD events or 1 event and ≥2 high-risk conditions. Patients were followed through December 31, 2017, for ASCVD events, including myocardial infarction, ischemic stroke, and major adverse limb events.Results: Overall, 15,366 patients (55.3%) with ASCVD met the definition of very high risk. Among patients with and without very high risk, the ASCVD event rate per 1,000 person-years was 53.1 (95% confidence interval [CI]: 50.1 to 56.1) and 17.0 (95% CI: 15.2 to 18.9), respectively. Among patients with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions, the ASCVD event rate per 1,000 person-years was 89.8 (95% CI: 82.2 to 98.0) and 41.3 (95% CI: 38.3 to 44.4), respectively. The age- and sex-adjusted hazard ratios for ASCVD events among patients with very high risk, overall, with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions versus those without very high risk were 2.98 (95% CI: 2.63 to 3.37), 4.89 (95% CI: 4.22 to 5.66), and 2.33 (95% CI: 2.04 to 2.66), respectively.Conclusions: The 2018 AHA/ACC cholesterol guideline directs intensive lipid-lowering therapy to adults with a very high ASCVD event rate. [ABSTRACT FROM AUTHOR]

Background Many adults without cerebrovascular disease report a history of stroke symptoms, which is associated with higher risk for stroke. Because stroke and coronary heart disease (CHD) share many risk factors, we examined the association between a history of stroke symptoms and incident CHD. Methods We analyzed data from 8999 black and 12,499 white REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a prior myocardial infarction, stroke or transitory ischemic attack enrolled in 2003–2007 (total participants = 21,498, all ≥ 45 years of age). A history of stroke symptoms (i.e., unilateral weakness, unilateral numbness, full-field vision loss, half-field vision loss, understanding problems and communication problems) was assessed at baseline using the Questionnaire for Verifying Stroke-Free Status. Participants were followed for incident CHD and CHD death through December 2011. Results Overall, 3432 (16.0%) participants reported a history of stroke symptoms (1771 [19.7%] blacks and 1661 [13.3%] whites). There were 701 incident CHD events including 209 CHD deaths over a median follow-up of 5.8 years. After adjustment for CHD risk factors, hazard ratios (95% confidence interval [95% CI]) for incident CHD associated with reporting any versus no stroke symptoms were 1.26 (1.04–1.51) in the overall population, 1.28 (0.99–1.65) among blacks and 1.23 (0.94–1.61) among whites. Multivariable-adjusted hazard ratios (95% CI) for CHD death associated with any versus no stroke symptoms were 1.50 (1.10–2.06) overall, 1.58 (1.07–2.32) among blacks and 1.41 (0.82–2.43) among whites. Conclusion A history of stroke symptoms is associated with a higher incidence of CHD among black and white adults. [ABSTRACT FROM AUTHOR]

Background: The use of statins increased among US adults with high coronary heart disease (CHD) risk after publication of the 2001 cholesterol treatment guidelines.Methods and Results: We analyzed the association between lipids and CHD among 9578 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants and 346,595 Kaiser Permanente Southern California (KPSC) members with baseline lipid measurements in 2003 to 2007. We performed the same analyses among 14,590 Atherosclerosis Risk In Communities (ARIC) study participants with lipid measurements in 1987 to 1989. Analyses were restricted to blacks and whites 45 to 64 years of age without CHD who were not taking statins at baseline. Total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured at baseline. Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and ratios of total to high-density lipoprotein cholesterol and triglycerides to high-density lipoprotein cholesterol were calculated. The prevalence of diabetes mellitus, history of stroke, and antihypertensive medication use increased at higher low-density lipoprotein cholesterol in ARIC but not in REGARDS or KPSC. Over 8.9 years of follow-up, 225 CHD events occurred in REGARDS, 6547 events in KPSC, and 583 events in ARIC. After multivariable adjustment, less favorable lipid levels were associated with higher hazard ratios for CHD in ARIC. These associations were attenuated in REGARDS and KPSC. For example, the hazard ratio associated with the highest versus lowest quartile of low-density lipoprotein cholesterol (≥ 146 versus ≤ 102 mg/dL) was 1.89 (95% confidence interval, 1.42-2.51) in ARIC, 1.25 (95% confidence interval, 0.81-1.92) in REGARDS, and 1.49 (95% confidence interval, 1.38-1.61) in KPSC.Conclusion: The association between lipids and CHD in contemporary studies may be attenuated by the preferential use of statins by high-risk individuals. [ABSTRACT FROM AUTHOR]

Background: Variability of blood pressure (BP) across outpatient visits is frequently dismissed as random fluctuation around a patient's underlying BP. Objective: To examine the association of visit-to-visit variability (VVV) of systolic BP (SBP) and diastolic BP with cardiovascular disease (CVD) and mortality outcomes. Design: Prospective cohort study. Setting: Post hoc analysis of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). Participants: 25 814 ALLHAT participants. Measurements: The VVV of SBP was defined as the SD across SBP measurements obtained at 7 visits conducted from 6 to 28 months after ALLHAT enrollment. Participants without CVD events during the first 28 months of follow-up were followed from the 28-month visit through the end of active ALLHAT follow-up. Outcomes included fatal coronary heart disease (CHD) or nonfatal myocardial infarction, all-cause mortality, stroke, and heart failure. Results: During follow-up, 1194 fatal CHD or nonfatal MI events, 1948 deaths, 606 strokes, and 921 heart failure events occurred. After multivariable adjustment, including for mean SBP, the hazard ratio comparing participants in the highest versus lowest quintile of SD of SBP (≥14.4 mm Hg vs. <6.5 mm Hg) was 1.30 (95% CI, 1.06 to 1.59) for fatal CHD or nonfatal MI, 1.58 (CI, 1.32 to 1.90) for all-cause mortality, 1.46 (CI, 1.06 to 2.01) for stroke, and 1.25 (CI, 0.97 to 1.61) for heart failure. Higher VVV of diastolic BP was also associated with CVD events and mortality. Limitation: Long-term outcomes were not available. Conclusion: Higher VVV of SBP is associated with an increased risk for CVD and mortality. Future studies should examine whether reducing VVV of BP lowers this risk. [ABSTRACT FROM AUTHOR]

Introduction: Microsize myocardial infarction (MI) is a recently described phenomenon consisting of events that meet rigorous criteria for MI but with very low peak troponin elevations (<0.5 ng/mL). We have shown that risk factors for microsize MIs are similar to those of usual MIs (troponin >0.5 ng/ml). However, there are few data available on the risk for cardiovascular outcome events and mortality following microsize MIs. Objectives: To compare the risk for cardiovascular outcome events and mortality following microsize vs. usual MIs in the national REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Methods: Prospective cohort analysis of REGARDS study participants without a history of MI who had an incident MI between 2003 and 2015. Incident MIs were classified as microsize MI (peak troponin <0.5 ng/ml) or usual MI (peak troponin >0.5 ng/ml). Participants with an incident MI were followed for heart failure, coronary revascularization, recurrent MI, fatal coronary heart disease (CHD), and mortality through December 31, 2015. Cox proportional hazards regression was used to assess the associations between MI type and outcomes. Results: Overall, 1,260 participants with incident MIs were included in the analysis (412 microsize MIs and 848 usual MIs). Participants with microsize MI were more likely to be older and black. After adjusting for confounders, microsize MIs were associated with a higher risk of recurrent MI, lower risk of fatal CHD, higher risk of late (>1.5 years after MI) revascularization, and a similar risk of the other outcomes after 5 years of follow up compared to usual MI (Table 1). Discussion: Microsize MIs have a prognostic value for future cardiovascular events and mortality comparable to usual MIs. These findings should encourage clinicians to both treat reversible risk factors for microsize MI and to initiate secondary prevention strategies post-MI until this emerging clinical entity is better understood. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a major risk factor for coronary heart disease (CHD) and is usually treated with statins. Few observational studies have examined associations between lipids and CHD in the era of widespread statin use. The objective of the current analysis was to contrast the association between serum lipids and incident coronary heart disease (CHD) among middle-aged adults before and after statin use became widespread. Methods: We analyzed data from 14,590 Atherosclerosis Risk In Communities (ARIC) study participants who were recruited in 1987-1989 (pre-statins), and 13,196 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants (9,578 not taking statins) who were recruited in 2003-2007 (poststatins). Our analysis was restricted to participants 45 to 64 years of age without a history of CHD at baseline. Total and HDL cholesterol (HDL-C) and fasting triglycerides (TG) were measured at baseline and used to calculate LDL-C, non- HDL-C, total-to-HDL-C ratio and total-to-TG ratio. Each lipid parameter was categorized into four levels based on REGARDS quartile cut-points. Results: In ARIC, participants with higher LDL-C were more likely to have diabetes and use antihypertensive medication, whereas these CHD risk factors were progressively less common at higher LDL-C in REGARDS participants not taking statins. Over a maximum 7 years of follow up, 513 and 278 incident CHD events occurred among ARIC and REGARDS participants, respectively. After multivariable adjustment, higher categories of each lipid marker (lower categories of HDL-C) were associated with a higher hazard ratio (HR) for CHD among ARIC participants, but not among REGARDS participants not taking statins (figure). No association between lipid markers and CHD was observed among REGARDS participants taking statins. DISCUSION: The current analysis suggests that the widespread preferential use of statins among high risk individuals may have obscured the association between lipids and incident CHD. [ABSTRACT FROM AUTHOR]

Background: Data from before the 2000s indicate that the majority of incident cardiovascular disease (CVD) events occur among US adults with systolic and diastolic blood pressure (SBP/DBP) ≥140/90 mm Hg. Over the past several decades, BP has declined and hypertension control has improved.Methods: We estimated the percentage of incident CVD events that occur at SBP/DBP <140/90 mm Hg in a pooled analysis of 3 contemporary US cohorts: the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), the MESA (Multi-Ethnic Study of Atherosclerosis), and the JHS (Jackson Heart Study) (n=31 856; REGARDS=21 208; MESA=6779; JHS=3869). Baseline study visits were conducted in 2003 to 2007 for REGARDS, 2000 to 2002 for MESA, and 2000 to 2004 for JHS. BP was measured by trained staff using standardized methods. Antihypertensive medication use was self-reported. The primary outcome was incident CVD, defined by the first occurrence of fatal or nonfatal stroke, nonfatal myocardial infarction, fatal coronary heart disease, or heart failure. Events were adjudicated in each study.Results: Over a mean follow-up of 7.7 years, 2584 participants had incident CVD events. Overall, 63.0% (95% confidence interval [CI], 54.9-71.1) of events occurred in participants with SBP/DBP <140/90 mm Hg; 58.4% (95% CI, 47.7-69.2) and 68.1% (95% CI, 60.1-76.0) among those taking and not taking antihypertensive medication, respectively. The majority of events occurred in participants with SBP/DBP <140/90 mm Hg among those <65 years of age (66.7%; 95% CI, 60.5-73.0) and ≥65 years of age (60.3%; 95% CI, 51.0-69.5), women (61.4%; 95% CI, 49.9-72.9) and men (63.8%; 95% CI, 58.4-69.1), and for whites (68.7%; 95% CI, 66.1-71.3), blacks (59.0%; 95% CI, 49.5-68.6), Hispanics (52.7%; 95% CI, 45.1-60.4), and Chinese-Americans (58.5%; 95% CI, 45.2-71.8). Among participants taking antihypertensive medication with SBP/DBP <140/90 mm Hg, 76.6% (95% CI, 75.8-77.5) were eligible for statin treatment, but only 33.2% (95% CI, 32.1-34.3) were taking one, and 19.5% (95% CI, 18.5-20.5) met the SPRINT (Systolic Blood Pressure Intervention Trial) eligibility criteria and may benefit from a SBP target goal of 120 mm Hg.Conclusions: Although higher BP levels are associated with increased CVD risk, in the modern era, the majority of incident CVD events occur in US adults with SBP/DBP <140/90 mm Hg. While absolute risk and cost-effectiveness should be considered, additional CVD risk-reduction measures for adults with SBP/DBP <140/90 mm Hg at high risk for CVD may be warranted. [ABSTRACT FROM AUTHOR]