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Environmental health research has suggested that fine particulate matter (PM 2.5 ) exposure can lead to high blood pressures, but it is unclear whether the impacts remain the same for systolic and diastolic blood pressures (SBP and DBP). This study aimed to examine whether the effects of PM 2.5 exposure on SBP and DBP differ using data from a predominantly non-Hispanic Black cohort collected between 2013 and 2019 in the US. PM 2.5 exposure was assessed based on a satellite-derived model across exposure durations from 1 to 36 months. The average PM 2.5 exposure level was between 9.5 and 9.8 μg/m 3 from 1 through 36 months. Mixed effects models were used to estimate the association of PM 2.5 with SBP, DBP, and related hypertension types, adjusted for potential confounders. A total of 6381 participants were included. PM 2.5 exposure was positively associated with both SBP and DBP. The association magnitudes depended on exposure durations. The association with SBP was null at the 1-month duration (β = 0.05, 95% CI: - 0.23, 0.33), strengthened as duration increased, and plateaued at the 24-month duration (β = 1.14, 95% CI: 0.54, 1.73). The association with DBP started with β = 0.29 (95% CI: 0.11, 0.47) at the 1-month duration, and plateaued at the 12-month duration (β = 1.61, 95% CI: 1.23, 1.99). PM 2.5 was associated with isolated diastolic hypertension (12-month duration: odds ratio = 1.20, 95% CI: 1.07, 1.34) and systolic-diastolic hypertension (12-month duration: odds ratio = 1.18, 95% CI: 1.10, 1.26), but not with isolated systolic hypertension. The findings suggest DBP is more sensitive to PM 2.5 exposure and support differing effects of PM 2.5 exposure on SBP and DBP. As elevation of SBP and DBP differentially predict CVD outcomes, this finding is relevant for prevention and treatment., (© 2024. The Author(s).)

Importance: Socioeconomically disadvantaged subpopulations are more vulnerable to fine particulate matter (PM2.5) exposure. However, as prior studies focused on individual-level socioeconomic characteristics, how contextual deprivation modifies the association of PM2.5 exposure with cardiovascular health remains unclear., Objective: To assess disparities in PM2.5 exposure association with cardiovascular disease among subpopulations defined by different socioeconomic characteristics., Design, Setting, and Participants: This cohort study used longitudinal data on participants with electronic health records (EHRs) from the All of Us Research Program between calendar years 2016 and 2022. Statistical analysis was performed from September 25, 2023, through February 23, 2024., Exposure: Satellite-derived 5-year mean PM2.5 exposure at the 3-digit zip code level according to participants' residential address., Main Outcome and Measures: Incident myocardial infarction (MI) and stroke were obtained from the EHRs. Stratified Cox proportional hazards regression models were used to estimate the hazard ratio (HR) between PM2.5 exposure and incident MI or stroke. We evaluated subpopulations defined by 3 socioeconomic characteristics: contextual deprivation (less deprived, more deprived), annual household income (≥$50 000, <$50 000), and race and ethnicity (non-Hispanic Black, non-Hispanic White). We calculated the ratio of HRs (RHR) to quantify disparities between these subpopulations., Results: A total of 210 554 participants were analyzed (40% age >60 years; 59.4% female; 16.7% Hispanic, 19.4% Non-Hispanic Black, 56.1% Non-Hispanic White, 7.9% other [American Indian, Asian, more than 1 race and ethnicity]), among whom 954 MI and 1407 stroke cases were identified. Higher PM2.5 levels were associated with higher MI and stroke risks. However, disadvantaged groups (more deprived, income <$50 000 per year, Black race) were more vulnerable to high PM2.5 levels. The disparities were most pronounced between groups defined by contextual deprivation. For instance, increasing PM2.5 from 6 to 10 μg/m3, the HR for stroke was 1.13 (95% CI, 0.85-1.51) in the less-deprived vs 2.57 (95% CI, 2.06-3.21) in the more-deprived cohort; 1.46 (95% CI, 1.07-2.01) in the $50 000 or more per year vs 2.27 (95% CI, 1.73-2.97) in the under $50 000 per year cohort; and 1.70 (95% CI, 1.35-2.16) in White individuals vs 2.76 (95% CI, 1.89-4.02) in Black individuals. The RHR was highest for contextual deprivation (2.27; 95% CI, 1.59-3.24), compared with income (1.55; 95% CI, 1.05-2.29) and race and ethnicity (1.62; 95% CI, 1.02-2.58)., Conclusions and Relevance: In this cohort study, while individual race and ethnicity and income remained crucial in the adverse association of PM2.5 with cardiovascular risks, contextual deprivation was a more robust socioeconomic characteristic modifying the association of PM2.5 exposure.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Aims: Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC., Methods and Results: This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156)., Conclusion: In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation., Competing Interests: Conflict of interest: M.D.S. has participated in scientific advisory boards with the following entities: Amgen, Agepha, Ionis, Novartis, Precision BioScience, Novo Nordisk, and New Amsterdam; and has served as a consultant for Ionis, Novartis, Regeneron, Aidoc, Kaneka, and Shanghai Pharma Biotherapeutics. C.L.S. has received honoraria from the National Institutes of Health for service on grant review panels. All other authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To investigate the joint relationship of health insurance and clinic visit with hypertension among underserved populations., Design: Population-based cohort study., Subjects: Data from 1092 participants from the Chicago Multiethnic Prevention and Surveillance Study (COMPASS) between 2013 and 2020 were analyzed., Measures: Five health insurance types were included: uninsured, Medicaid, Medicare, private, and other. Clinic visit over past 12 months were retrieved from medical records and categorized into 4 groups: no clinic visit, 1-3 visits, 4-7 visits, >7 visits., Analysis: Inverse-probability weighted logistic regression was used to estimate odds ratios (OR) and 95% confidence interval (CI) for hypertension status according to health insurance and clinic visit. Models were adjusted for individual socio-demographic variables and medical history., Results: The study population was predominantly Black (>85%) of low socioeconomic status. Health insurance was not associated with more clinic visit. Measured hypertension was more frequently found in private insurance (OR = 6.48, 95% CI: 1.92-21.85) compared to the uninsured group, while 1-3 clinic visits were associated with less prevalence (OR = .59, 95% CI: .35-1.00) compared to no clinic visit. These associations remained unchanged when health insurance and clinic visit were adjusted for each other., Conclusion: In this study population, private insurance was associated with higher measured hypertension prevalence compared to no insurance. The associations of health insurance and clinic visit were independent of each other., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study identified barriers to participation in supervised exercise therapy covered by the Centers for Medicare and Medicaid Services (CMS), reported by people with lower extremity peripheral artery disease (PAD)., Methods: People with PAD participating in research studies of walking impairment due to PAD in the Chicagoland area were asked to complete a questionnaire between March 15, 2019, and July 12, 2022, assessing their experience and attitudes about supervised exercise therapy. Participants were identified using mailed postcards to people aged 50 and older in Chicagoland, from medical centers in Chicago, and using bus and train advertisements. The questionnaire was developed based on focus group feedback from people with PAD., Results: Of 516 participants with PAD approached, 489 (94.8%) completed the questionnaire (mean age: 71.0 years [standard deviation: 8.7], mean ankle-brachial index: 0.71 [standard deviation: 0.25]; 204 [41.7%] women and 261 [53.4%] Black). Of the 489 participants, 416 (85.1%) reported that their physician had never prescribed or recommended supervised exercise therapy. Overall, 357 (73.2%) reported willingness to travel three times weekly to the medical center for supervised exercise participation. However, of these, 214 (59.9%) reported that they were unwilling or unable to pay the $11 per exercise session copay required for supervised exercise covered by CMS. Of 51 people with PAD who reported prior participation in supervised exercise, only 5 (9.8%) completed the 12 weeks of supervised exercise therapy covered by CMS and 29 (56.9%) completed 6 or fewer weeks. Of 131 (26.8%) unwilling to travel three times weekly to a center for supervised exercise, the most common reasons for unwillingness to participate were "too time-consuming" (55.0%), "too inconvenient" (45.8%), and "lack of interest in treadmill exercise" (28.2%)., Conclusions: Approximately 2 to 4 years after CMS began covering supervised exercise for PAD, most people with PAD in this study from a large urban area had not participated in supervised exercise therapy. Of those who participated, most completed fewer than half of the sessions covered by CMS. The required CMS copayment was a common barrier to supervised exercise participation by people with PAD., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Understanding the relationship between hypertension and spatial accessibility of primary care can inform interventions to improve hypertension control and awareness, especially among disadvantaged populations. This study aims to investigate the association between spatial accessibility of primary care and hypertension control and awareness., Methods: Participant data from the COMPASS (Chicago Multiethnic Prevention and Surveillance Study) between 2013 and 2019 were analyzed. All participants were geocoded. Locations of primary care providers in Chicago were obtained from MAPSCorps. A score was generated for spatial accessibility of primary care using an enhanced 2-step floating catchment area method. A higher score indicates greater accessibility. Measured hypertension was defined as systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg. Logistic regression was used to estimate odds ratio and 95% CI for hypertension status in relation to accessibility score quartiles., Results: Five thousand ninety-six participants (mean age, 53.4±10.8) were included. The study population was predominantly non-Hispanic black (84.0%), over 53% reported an annual household income <$15 000, and 37.3% were obese. Measured hypertension prevalence was 78.7% in this population, among which 37.7% were uncontrolled and 41.0% were unaware. A higher accessibility score was associated with lower measured hypertension prevalence. In fully adjusted models, compared with the first (lowest) quartile of accessibility score, the odds ratio strengthened from 0.82 (95% CI, 0.67-1.01) for the second quartile to 0.75 (95% CI, 0.62-0.91) for the third quartile, and further to 0.73 (95% CI, 0.60-0.89) for the fourth (highest) quartile. The increasing trend had a P <0.01. Similar associations were observed for both uncontrolled and unaware hypertensions. When stratified by neighborhood socioeconomic status, a higher accessibility score was associated with lower rates of unaware hypertension in both disadvantaged and nondisadvantaged neighborhoods., Conclusions: Better spatial accessibility of primary care is associated with improved hypertension awareness and control.

Objective: N-Terminal pro B-type Natriuretic Peptide (NT-proBNP), a biomarker of heart failure (HF) has been associated with early menopause. We evaluated the modifying role of early menopause on the association of NT-proBNP with incident HF, and separately for HF subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF)., Methods: We included 4,352 postmenopausal women including 1,174 with early menopause, ages 63.5 ± 5.5 years, without prevalent HF at the Atherosclerosis Risk in Communities study Visit 4. Binary log-transformation was performed for NT-proBNP. Cox proportional hazards models were used to examine the association of NT-proBNP with incident HF, and separately for incident HFpEF and incident HFrEF, testing for effect modification by early menopause and adjusting for HF risk factors., Results: We observed 881 HF events over a mean follow-up of 16.5 years. The interaction terms of NT-proBNP and early menopause were not significant for incident HF (Pinteraction 0.95) and incident HFpEF (Pinteraction 0.17) but were significant for incident HFrEF (Pinteraction 0.03). The adjusted hazard ratios resulting from each doubling of NT-proBNP levels amongst women with and without early menopause were 1.33 (1.20-1.47) and 1.34 (1.24-1.44), respectively, for incident HF; 1.57 (1.34-1.86) and 1.38 (1.24-1.54), respectively, for incident HFpEF; and 1.68 (1.42-1.99) and 1.36 (1.22-1.52), respectively, for incident HFrEF., Conclusions: The association of NT-proBNP with incident HFpEF is similar irrespective of early menopause status. However, the association of NT-proBNP with incident HFrEF is greater among women with early menopause when compared to those without early menopause., Competing Interests: Financial disclosure/conflicts of interest: C. B. has received grant/research support (to his institution) from Abbott Diagnostic, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, and Roche Diagnostic, and has been a consultant for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma Inc, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. A. G. B. has received funding from the National Institute of Health. The other authors have nothing to disclose., (Copyright © 2022 by The North American Menopause Society.)

Importance: Supervised high-intensity walking exercise that induces ischemic leg symptoms is the first-line therapy for people with lower-extremity peripheral artery disease (PAD), but adherence is poor., Objective: To determine whether low-intensity home-based walking exercise at a comfortable pace significantly improves walking ability in people with PAD vs high-intensity home-based walking exercise that induces ischemic leg symptoms and vs a nonexercise control., Design, Setting, and Participants: Multicenter randomized clinical trial conducted at 4 US centers and including 305 participants. Enrollment occurred between September 25, 2015, and December 11, 2019; final follow-up was October 7, 2020., Interventions: Participants with PAD were randomized to low-intensity walking exercise (n = 116), high-intensity walking exercise (n = 124), or nonexercise control (n = 65) for 12 months. Both exercise groups were asked to walk for exercise in an unsupervised setting 5 times per week for up to 50 minutes per session wearing an accelerometer to document exercise intensity and time. The low-intensity group walked at a pace without ischemic leg symptoms. The high-intensity group walked at a pace eliciting moderate to severe ischemic leg symptoms. Accelerometer data were viewable to a coach who telephoned participants weekly for 12 months and helped them adhere to their prescribed exercise. The nonexercise control group received weekly educational telephone calls for 12 months., Main Outcomes and Measures: The primary outcome was mean change in 6-minute walk distance at 12 months (minimum clinically important difference, 8-20 m)., Results: Among 305 randomized patients (mean age, 69.3 [SD, 9.5] years, 146 [47.9%] women, 181 [59.3%] Black patients), 250 (82%) completed 12-month follow-up. The 6-minute walk distance changed from 332.1 m at baseline to 327.5 m at 12-month follow-up in the low-intensity exercise group (within-group mean change, -6.4 m [95% CI, -21.5 to 8.8 m]; P = .34) and from 338.1 m to 371.2 m in the high-intensity exercise group (within-group mean change, 34.5 m [95% CI, 20.1 to 48.9 m]; P < .001) and the mean change for the between-group comparison was -40.9 m (97.5% CI, -61.7 to -20.0 m; P < .001). The 6-minute walk distance changed from 328.1 m at baseline to 317.5 m at 12-month follow-up in the nonexercise control group (within-group mean change, -15.1 m [95% CI, -35.8 to 5.7 m]; P = .10), which was not significantly different from the change in the low-intensity exercise group (between-group mean change, 8.7 m [97.5% CI, -17.0 to 34.4 m]; P = .44). Of 184 serious adverse events, the event rate per participant was 0.64 in the low-intensity group, 0.65 in the high-intensity group, and 0.46 in the nonexercise control group. One serious adverse event in each exercise group was related to study participation., Conclusions and Relevance: Among patients with PAD, low-intensity home-based exercise was significantly less effective than high-intensity home-based exercise and was not significantly different from the nonexercise control for improving 6-minute walk distance. These results do not support the use of low-intensity home-based walking exercise for improving objectively measured walking performance in patients with PAD., Trial Registration: ClinicalTrials.gov Identifier: NCT02538900.

Objective: We investigated isolated and joint effects of early menopause (occurrence before 45 y of age) and high-sensitivity cardiac troponin T elevation (hs-cTnT ≥ 14 ng/L) on heart failure (HF) incidence in postmenopausal women., Methods: We included 2,276 postmenopausal women, aged 67-90 years, with hs-cTnT measurements and without prevalent HF from the Atherosclerosis Risk in Communities study Visit 5 (2011-2013). Women were categorized according to early menopause and hs-cTnT group. Cox proportional hazards models were used for analysis., Results: Over a median follow-up of 5.5 years, we observed 104 HF events. The incidence rates of HF were greater in women with hs-cTnT elevation when compared to those without hs-cTnT elevation. In unadjusted analysis, the hazard ratios for incident HF were threefold greater in women with hs-cTnT elevation, with or without early menopause, (3.03 [95% CI, 1.59-5.77]) and (3.29 [95% CI, 2.08-5.21]), respectively, but not significantly greater in women with early menopause without hs-cTnT elevation, when compared to women with neither early menopause nor hs-cTnT elevation at Visit 5. After adjusting for HF risk factors and NT-pro B-type natriuretic peptide, these associations were attenuated and became nonsignificant for women with hs-cTnT elevation, but became stronger and significant for women with early menopause without hs-cTnT elevation (2.39 [95% CI, 1.28-4.46])., Conclusions: Irrespective of early menopause status, hs-cTnT elevation is associated with greater HF incidence but this association is partially explained by HF risk factors. Even in the absence of hs-cTnT elevation, early menopause is significantly associated with HF incidence after accounting for HF risk factors., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2021 by The North American Menopause Society.)

Background It has been widely recognized that obstructive sleep apnea (OSA) is linked to cardiovascular disease. Yet, randomized controlled studies failed to demonstrate a clear cardiovascular benefit from OSA treatment, mainly because of poor adherence to continuous positive airway pressure (CPAP). To date, no prior study has assessed the effect of CPAP treatment on daytime resting heart rate, a strong predictor of adverse cardiovascular outcomes and mortality. Methods and Results We conducted a randomized controlled study in 39 participants with OSA and prediabetes, who received either in-laboratory all-night (ie, optimal) CPAP or an oral placebo for 2 weeks. During daytime, participants continued daily activities outside the laboratory. Resting heart rate was continuously assessed over 19 consecutive days and nights using an ambulatory device consisting of a single-lead ECG and triaxis accelerometer. Compared with placebo, CPAP reduced daytime resting heart rate (treatment difference, -4.1 beats/min; 95% CI, -6.5 to -1.7 beats/min; P =0.002). The magnitude of reduction in daytime resting heart rate after treatment significantly correlated with the magnitude of decrease in plasma norepinephrine, a marker of sympathetic activity ( r =0.44; P =0.02), and the magnitude of decrease in OSA severity (ie, apnea-hypopnea index [ r =0.48; P =0.005], oxygen desaturation index [ r =0.50; P =0.003], and microarousal index [ r =0.57; P <0.001]). Conclusions This proof-of-concept randomized controlled study demonstrates, for the first time, that CPAP treatment, when optimally used at night, reduces resting heart rate during the day, and therefore has positive cardiovascular carry over effects. These findings suggest that better identification and treatment of OSA may have important clinical implications for cardiovascular disease prevention. Registration URL: https:/// www.clini​caltr​ials.gov; Unique identifier: NCT01156116.

Background Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD. Methods and Results Macrophages, satellite cells, and extracellular matrix in gastrocnemius muscles from 25 patients with PAD and 7 patients without PAD were quantified using immunohistochemistry. Among patients with PAD, both the absolute number and percentage of cluster of differentiation (CD) 11b+CD206+ M2-like macrophages positively correlated to satellite cell number ( r =0.461 [ P =0.023] and r =0.416 [ P =0.042], respectively) but not capillary density or extracellular matrix. The number of CD11b+CD206- macrophages negatively correlated to 4-meter walk tests at normal ( r =-0.447, P =0.036) and fast pace ( r =-0.510, P =0.014). Extracellular matrix occupied more muscle area in PAD compared with non-PAD (8.72±2.19% versus 5.30±1.03%, P <0.001) and positively correlated with capillary density ( r =0.656, P <0.001). Conclusions Among people with PAD, higher CD206+ M2-like macrophage abundance was associated with greater satellite cell numbers and muscle fiber size. Lower CD206- macrophage abundance was associated with better walking performance. Further study is needed to determine whether CD206+ macrophages are associated with ongoing reparative processes enabling skeletal muscle adaptation to damage with PAD. Registration URL: https://www.clini​caltr​ials.gov; Unique identifiers: NCT00693940, NCT01408901, NCT0224660.

Background Patients with peripheral artery disease (PAD) undergo frequent episodes of ischemia-reperfusion in lower extremity muscles that may negatively affect mitochondrial health and are associated with impaired mobility. We hypothesized that skeletal muscle from PAD patients will show high mitochondrial DNA heteroplasmy, especially in regions more susceptible to oxidative damage, such as the displacement loop, and that the degree of heteroplasmy will be correlated with the severity of ischemia and mobility impairment. Methods and Results Mitochondrial mutations and deletions and their relative abundance were identified by targeted mitochondrial DNA sequencing in biopsy specimens of gastrocnemius muscle from 33 PAD (ankle brachial index <0.9) and 9 non-PAD (ankle brachial index >0.9) subjects aged ≥60 years. The probability of heteroplasmy per DNA base was significantly higher for PAD subjects than non-PAD within each region. In adjusted models, PAD was associated with higher heteroplasmy than non-PAD ( P =0.003), but the association was limited to microheteroplasmy, that is heteroplasmy found in 1% to 5% of all mitochondrial genomes ( P =0.004). Heteroplasmy in the displacement loop and coding regions were significantly higher for PAD than non-PAD subjects after adjustment for age, sex, race, and diabetes mellitus ( P =0.037 and 0.004, respectively). Low mitochondrial damage, defined by both low mitochondrial DNA copy number and low microheteroplasmy, was associated with better walking performance. Conclusions People with PAD have higher "low frequency" heteroplasmy in gastrocnemius muscle compared with people without PAD. Among people with PAD, those who had evidence of least mitochondrial damage, had better walking performance than those with more mitochondrial damage. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02246660.

The elimination of specific dietary cholesterol target recommendations in recent guidelines has raised questions about its role with respect to cardiovascular disease. This advisory was developed after a review of human studies on the relationship of dietary cholesterol with blood lipids, lipoproteins, and cardiovascular disease risk to address questions about the relevance of dietary cholesterol guidance for heart health. Evidence from observational studies conducted in several countries generally does not indicate a significant association with cardiovascular disease risk. Although meta-analyses of intervention studies differ in their findings, most associate intakes of cholesterol that exceed current average levels with elevated total or low-density lipoprotein cholesterol concentrations. Dietary guidance should focus on healthy dietary patterns (eg, Mediterranean-style and DASH [Dietary Approaches to Stop Hypertension]-style diets) that are inherently relatively low in cholesterol with typical levels similar to the current US intake. These patterns emphasize fruits, vegetables, whole grains, low-fat or fat-free dairy products, lean protein sources, nuts, seeds, and liquid vegetable oils. A recommendation that gives a specific dietary cholesterol target within the context of food-based advice is challenging for clinicians and consumers to implement; hence, guidance focused on dietary patterns is more likely to improve diet quality and to promote cardiovascular health.

Background: High-sensitivity cardiac troponin T (hs-cTnT) is individually associated with incident hypertension (HTN) and cardiovascular disease (CVD) events. We hypothesize that the increases in hs-cTnT with increases in blood pressure will be related to higher incidence of CVD., Methods: The Cardiovascular Health Study is a longitudinal cohort of older adults. Those with hs-cTnT data and CVD risk factors at baseline and follow-up (2-3 years later) were stratified based on systolic blood pressure (SBP; optimal: <120 mm Hg, intermediate: 120-139 mm Hg, elevated: ≥140 mm Hg) and hs-cTnT (undetectable: <5 ng/l, detectable: 5-13 ng/l, elevated: ≥14 ng/l) categories. SBP and hs-cTnT were classified as increased or decreased if they changed categories between exams, and stable if they did not. Cox regression evaluated incident CVD events over an average 9-year follow-up., Results: Among 2,219 adults, 510 (23.0 %) had decreased hs-cTnT, 1,279 (57.6 %) had stable hs-cTnT, and 430 (19.4 %) had increased hs-cTnT. Those with increased hs-cTnT had a higher CVD risk with stable SBP (hazard ratio [HR]: 1.28 [1.04-1.57], P = 0.02) or decreased SBP (HR: 1.57 [1.08-2.28], P = 0.02) compared to those within the same SBP group but a stable hs-cTnT. In those with lower SBP at follow-up, there was an inverse relation between diastolic blood pressure (DBP) and risk of CVD events in those with increased hs-cTnT (HR: 0.44 per 10 mm Hg increase, P < 0.01)., Conclusion: An increase in hs-cTnT over time is associated with a higher risk of CVD even when the blood pressure is stable or decreases over time., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? Methods Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. Results Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (ie, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome.

Little is known about the prognostic significance of specific characteristics of magnetic resonance imaging (MRI) measured plaque in the superficial femoral artery (SFA). Associations of MRI-measured plaque quantity, lumen area, and plaque composition in the SFA with subsequent mobility loss were studied in people with lower extremity peripheral artery disease (PAD). Participants with an ankle-brachial index (ABI) < 1.00 were identified from Chicago medical centers and underwent direct visualization of atherosclerotic plaque in the SFA using MRI. Participants were followed annually for up to 4 years. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or walk one-quarter of a mile without assistance among participants without mobility impairment at baseline. Analyses adjusted for age, sex, race, comorbidities, ABI, physical activity, and other confounders. Of 308 PAD participants without baseline mobility impairment, 100 (32.5%) developed mobility loss during follow-up. Compared to the lowest mean plaque area tertile at baseline, participants in the highest (worst) plaque area tertile had a higher rate of mobility loss (hazard ratio (HR) = 2.08, 95% confidence interval (CI) = 1.14-3.79, p = 0.018). Compared to the highest mean lumen area tertile, the smallest (worst) mean lumen area tertile was associated with greater mobility loss (HR = 2.18, 95% CI = 1.20-3.96, p = 0.011). Neither lipid rich necrotic core nor calcium in the SFA were associated with mobility loss. In conclusion, greater plaque quantity and smaller lumen area in the proximal SFA, but not lipid rich necrotic core or calcium, were associated with higher mobility loss in people with PAD.

Changes in behavior are necessary to apply genomic discoveries to practice. We prospectively studied medication changes made by providers representing eight different medicine specialty clinics whose patients had submitted to preemptive pharmacogenomic genotyping. An institutional clinical decision support (CDS) system provided pharmacogenomic results using traffic light alerts: green = genomically favorable, yellow = genomic caution, red = high risk. The influence of pharmacogenomic alerts on prescribing behaviors was the primary endpoint. In all, 2,279 outpatient encounters were analyzed. Independent of other potential prescribing mediators, medications with high pharmacogenomic risk were changed significantly more often than prescription drugs lacking pharmacogenomic information (odds ratio (OR) = 26.2 (9.0-75.3), P < 0.0001). Medications with cautionary pharmacogenomic information were also changed more frequently (OR = 2.4 (1.7-3.5), P < 0.0001). No pharmacogenomically high-risk medications were prescribed during the entire study when physicians consulted the CDS tool. Pharmacogenomic information improved prescribing in patterns aimed at reducing patient risk, demonstrating that enhanced prescription decision-making is achievable through clinical integration of genomic medicine., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

Objectives: The aim of this study was to describe associations of the presence of lipid-rich necrotic core (LRNC) in the proximal superficial femoral artery (SFA) with lower extremity peripheral artery disease (PAD) event rates and systemic cardiovascular event rates., Background: LRNC in the coronary and carotid arteries is associated with adverse outcomes but has not been studied previously in lower extremity arteries., Methods: Participants with ankle-brachial index (ABI) values <1.00 were identified from Chicago medical centers and followed annually. Magnetic resonance imaging was used to characterize SFA atherosclerotic plaque at baseline. Medical records for hospitalizations and procedures after baseline were adjudicated for lower extremity revascularization, amputation, and critical limb ischemia and also for new coronary events, ischemic stroke, and mortality., Results: Of 254 participants with PAD, 62 (24%) had LRNC and 149 (59%) had calcium in the SFA at baseline. Cox regression analyses were adjusted for age, sex, race, comorbidities, baseline ABI, and other confounders. SFA LRNC was associated with an increased incidence of the combined outcome of lower extremity amputation, critical limb ischemia, ABI decline >0.15, and revascularization at 47-month follow-up (hazard ratio: 2.18; 95% confidence interval: 1.27 to 3.75; p = 0.005). The association of SFA LRNC with PAD events was maintained even when this combined outcome excluded lower extremity revascularization (hazard ratio: 2.58; 95% confidence interval: 1.25 to 5.33; p = 0.01). LRNC in the SFA was not associated with all-cause mortality, acute coronary events, or stroke., Conclusions: Among patients with PAD, LRNC in the SFA was associated with higher rates of clinical PAD events, and this association was independent of ABI. Further study is needed to determine whether interventions that reduce SFA LRNC prevent PAD events., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Despite growing clinical use of genomic information, patient perceptions of genomic-based care are poorly understood. We prospectively studied patient-physician pairs who participated in an institutional pharmacogenomic implementation program. Trust/privacy/empathy/medical decision-making (MDM)/personalized care dimensions were assessed through patient surveys after clinic visits at which physicians had access to preemptive pharmacogenomic results (Likert scale, 1 = minimum/5 = maximum; mean [SD]). From 2012-2015, 1,261 surveys were issued to 507 patients, with 792 (62.8%) returned. Privacy, empathy, MDM, and personalized care scores were significantly higher after visits when physicians considered pharmacogenomic results. Importantly, personalized care scores were significantly higher after physicians used pharmacogenomic information to guide medication changes (4.0 [1.4] vs. 3.0 [1.6]; P < 0.001) compared with prescribing visits without genomic guidance. Multivariable modeling controlling for clinical factors confirmed personalized care scores were more favorable after visits with genomic-influenced prescribing (odds ratio [OR] = 3.26; 95% confidence interval [CI] = (1.31-8.14); P < 0.05). Physicians seem to individualize care when utilizing pharmacogenomic results and this decision-making augmentation is perceived positively by patients., (© 2016 American Society for Clinical Pharmacology and Therapeutics.)

Background: Patients with celiac disease (CD) may be at an increased risk of cardiovascular disease (CVD), yet CVD risk factors are not well defined in CD. The validated Framingham Heart Study 10-year general CVD risk score (FRS) that incorporates traditional CVD risk factors including body mass index (BMI) has not been previously studied in CD patients., Aims: To compare BMI and FRS in CD patients with population-based controls., Methods: Biopsy-proven CD patients were ascertained retrospectively and data on BMI, systolic blood pressure, hypertension, smoking status, and diabetes were obtained at initial and follow-up visits. FRS was calculated and compared with 4 matched general population non-CD controls from the 2009 to 2010 National Health and Nutrition Examination Survey (NHANES)., Results: Of 258 total CD patients, 38.3% were overweight or obese compared with 69.8% of controls (P<0.001). In total, 174 CD patients met the inclusion criteria for FRS calculation. Of these, the median FRS was lower in CD patients compared with controls (3.9 vs. 4.2; P=0.011). In CD patients, tobacco use was significantly lower (P<0.001), whereas systolic blood pressure was significantly higher (P<0.01) than controls., Conclusions: Global CVD risk is lower among patients with CD compared with population controls. Lower BMI and tobacco use among CD patients could account for this difference. These results suggest that factors other than those measured by FRS could contribute to the increased risk of CVD in CD observed in some studies.

Background: Although carotid intima-media thickness (CIMT) assesses the structural properties of the carotid artery, it does not assess the mechanical properties of the vessel., Methods: The carotid arteries of 71 adult patients were evaluated with CIMT, and automated border detection computed vessel stiffness, compliance, elasticity, and distensibility., Results: CIMT and mechanical properties were differentially affected by traditional cardiac risk factors, with age dominating for CIMT, and age, diabetes, and smoking dominating for mechanical variables. There was a moderate linear correlation between CIMT and the distensibility coefficient (r = -0.54), but there were weak associations with other parameters of dynamic vessel function. When patients were separated into risk groups, the mechanical vascular parameters' classification frequently differed from the CIMT classification. This was particularly notable for patients with intermediate CIMT values, who were reclassified as low or high risk by mechanical parameters 45% of the time., Conclusion: We found that it is feasible to assess the cross-sectional area of the carotid artery using automatic border detection, which allows a novel method of determining carotid mechanical properties. These functional characteristics are often discordant with CIMT, suggesting that mechanical properties may be an important adjunct to the CIMT when evaluating the carotid artery., (2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

The CHICAGO study (Carotid Intima-Media Thickness in Atherosclerosis Using Pioglitazone) tested the hypothesis that pioglitazone would have a beneficial effect for reducing CIMT progression, compared with glimepiride. Treatment with pioglitazone produced improvement in several parameters, such as systolic blood pressure and lipid levels, including a 14% increase in HDL cholesterol, and reduced CIMT progression, compared with glimepiride. However, only the beneficial effect on HDL cholesterol predicted its beneficial effect for reducing CIMT progression. The following review examines data from additional studies evaluating how pioglitazone and HDL levels modify cardiovascular risk.

Background: Brain natriuretic peptide (BNP) is useful in diagnosing congestive heart failure (CHF) in patients presenting in the emergency department with acute dyspnea. We prospectively tested the utility of BNP for discriminating ARDS vs cardiogenic pulmonary edema (CPE)., Methods: We enrolled ICU patients with acute hypoxemic respiratory failure and bilateral pulmonary infiltrates who were undergoing right-heart catheterization (RHC) to aid in diagnosis. Patients with acute coronary syndrome, end-stage renal disease, recent coronary artery bypass graft surgery, or preexisting left ventricular ejection fraction /= 1,200 pg/mL, BNP had a specificity of 92% for CPE. Higher levels of BNP were associated with a decreased odds for ARDS (odds ratio, 0.4 per log increase; p = 0.007) after adjustment for age, history of CHF, and right atrial pressure. BNP was associated with in-hospital mortality (p = 0.03) irrespective of the final diagnosis and independent of APACHE (acute physiology and chronic health evaluation) II score., Conclusion: In ICU patients with hypoxemic respiratory failure, BNP appears useful in excluding CPE and identifying patients with a high probability of ARDS, and was associated with mortality in patients with both ARDS and CPE. Larger studies are necessary to validate these findings.

Purpose: This study was conducted to better understand how older African Americans with diabetes view their illness, and to develop a conceptual framework for approaching their care., Methods: Researchers conducted interviews of 19 African American patients 65 years or older who attended clinics at an urban academic medical center. The mean age of the patients was 73 years, 58% were female, 63% had a complication from diabetes, and 58% were taking insulin. Patients were asked open-ended questions about how diabetes affected their lives and their attitudes toward treatment. Data were analyzed through a grounded-theory perspective., Results: Patients showed variation in the degree to which they believed that diabetes affected their lives and how aggressive they wished treatment to be. Themes included issues of quality of life, health beliefs, and the social context. Paradoxical, contradictory statements were common, expressing ambivalence and uncertainty regarding the effect of the illness and the treatment., Conclusions: Wide variation exists in the attitudes of older African Americans toward their diabetes and treatment. Patients frequently expressed ambivalence toward the care of their illness. Providers should explore these issues and help patients resolve their ambivalence if patient preferences are to be respected in the overall treatment plan.

Binding of HSV-1 to cells is mediated by interactions of virion glycoproteins gC and/or gB with heparin sulfate (HS) glycosaminoglycans on cell surface proteoglycans. HS and the related glycosaminoglycan, heparin, comprise a family of heterogeneous carbohydrates composed of long, unbranched polysaccharides modified, for example, by sulfations and acetylations. To define the specific features of HS important for viral binding, we took advantage of the structural similarities between heparin and cell surface HS and compared the ability of chemically modified heparin compounds to inhibit the binding of viral particles to the cell surface and subsequent plaque formation. Because binding presumably involves multiple, complex interactions between both known heparin-binding glycoproteins, gC and gB, and cell surface HS, we compared the effects of modified heparin compounds on the binding and subsequent plaque formation of wild-type and gC-negative strains of HSV-1 and, in select cases, the binding of gB-negative virus to cells. We identified specific structural features of heparin essential for the inhibition of viral binding. For example, both N-sulfation and 6-O-sulfation must be important determinants since desulfation of heparin at these sites abolished or decreased the antiviral activity of heparin. Moreover, we found that the antiviral activity of heparin was independent of its anticoagulant activity. Carboxyl-reduced and 2,3-O-desulfated heparin selectively inhibited binding of gC-positive viruses (wild-type or a gB-negative strain) to cells, but had little or no inhibitory effect on binding and subsequent plaque formation for a gC-deletion virus. These results suggest that gC and gB interact with different structural features of HS.