Aims Lipoprotein(a) [Lp(a)] levels are generally constant throughout an individual’s lifetime, an... more Aims Lipoprotein(a) [Lp(a)] levels are generally constant throughout an individual’s lifetime, and current guidelines recommend that a single measurement is sufficient to assess the risk of coronary artery disease (CAD). However, it is unclear whether a single measurement of Lp(a) in individuals with acute myocardial infarction (MI) is indicative of the Lp(a) level six months following the event. Methods and results Lp(a) levels were obtained from individuals with non–ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI) (n = 99) within 24 h of hospital admission and after six months, who were enrolled in two randomized trials of evolocumab and placebo, and in individuals with NSTEMI or STEMI (n = 9) who enrolled in a small observation arm of the two protocols and did not receive study drug, but whose levels were obtained at the same time points. Median Lp(a) levels increased from 53.5 nmol/L (19, 165) during hospital admission to 58.0 nmol/L (14....
Our objective was to assess whether human immunodeficiency virus (HIV)-infection directly or indi... more Our objective was to assess whether human immunodeficiency virus (HIV)-infection directly or indirectly promotes the progression of clinical characteristics of coronary artery disease (CAD). 300 African Americans with asymptomatic CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV-infected) who underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years) were randomly selected from 1429 participants of a prospective epidemiological study between May 2004 and August 2015. We calculated Agatston-scores, number of coronary plaques and segment stenosis score (SSS). Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use on CAD. There was no significant difference in annual progression rates between HIV-infected and—uninfected regarding Agatston-scores (10.8 ± 25.1/year vs. 7.2 ± 17.8/year, p = 0.17), the number of plaques (0.2 ± 0.3/year vs. 0.3 ± 0.5/year, p = 0.11) or SSS (0.5 ...
Background/Introduction Cross-sectional studies are inconsistent on the potential independent adv... more Background/Introduction Cross-sectional studies are inconsistent on the potential independent adverse effects of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD). Furthermore, there is no information on the potential effects of HIV-infection on plaque volumes. Also, only the independent effects of HIV-infection on CAD have been investigated. Purpose In a prospective longitudinal observational cohort, we wished to assess whether HIV-infection accelerates CAD independently, or by acting in synergistic fashion with conventional and nonconventional cardiovascular risk factors to accelerate disease progression as assessed by clinical and volumetric parameters of CAD on coronary CT angiography (CCTA). Methods Overall, 300 asymptomatic individuals without cardiovascular symptoms but with CCTA-confirmed coronary plaques (210 males, age: 48.0±7.2 years) with or without HIV (226 HIV-infected) prospectively underwent CCTA at two time points (mean follow-up: 4.0±2.3...
Progress in neuro-psychopharmacology & biological psychiatry, Jan 2, 2018
Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individua... more Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individuals on antiretroviral therapy (ART), and that HIV itself may accelerate aging, the issue of whether cocaine use plays a role in HIV-associated aging in HIV-infected cocaine users has not been reported. The goals of this study were (1) to explore factor(s) associated with peripheral blood leukocyte telomere length, a marker of cellular replicative history, and telomere shortening in HIV-infected individuals, and (2) to assess whether cocaine use plays a role in accelerating telomere shortening in cocaine users with HIV infection. Between June 2010 and December 2016, 147 HIV-infected participants in Baltimore, Maryland, were enrolled in a cross-sectional study investigating factor(s) associated with telomere length. Of these 147, 93 participated in a follow-up study to examine factor(s) associated with telomere shortening. Robust regression model was used to analyze cross-sectional data and...
HIV+ individuals experience an increased burden of coronary artery disease (CAD) not adequately a... more HIV+ individuals experience an increased burden of coronary artery disease (CAD) not adequately accounted for by traditional CAD risk factors. Coronary endothelial function (CEF), a barometer of vascular health, is depressed early in atherosclerosis and predicts future events but has not been studied in HIV+ individuals. We tested whether CEF is impaired in HIV+ subjects without CAD as compared to an HIV- population matched for cardiac risk factors. In this observational study, CEF was measured noninvasively by quantifying isometric handgrip exercise (IHE)-induced changes in coronary vasoreactivity with MRI in 18 participants with HIV but no CAD (HIV+CAD-, based on prior imaging), 36 age- and cardiac risk factor-matched healthy participants with neither HIV nor CAD (HIV-CAD-), 41 subjects with no HIV but with known CAD (HIV-CAD+) and 17 subjects with both HIV and CAD (HIV+CAD+). CEF was significantly depressed in HIV+CAD- subjects as compared to that of risk-factor-matched HIV-CAD- ...
Although rapid progression of coronary atherosclerosis was observed in chronic cocaine users, it ... more Although rapid progression of coronary atherosclerosis was observed in chronic cocaine users, it is unknown whether reduced cocaine use retards the progression of atherosclerosis. We investigated whether reduced cocaine use over a 12-month period was associated with coronary plaque regression in cocaine users. Fifteen African American chronic cocaine users with previously coronary computed tomography angiography (CCTA)-confirmed >50% coronary stenosis in Baltimore, Maryland, were enrolled in a study to investigate whether reduced cocaine use is associated with changes in coronary plaque burden over a 12-month period of cash-based incentive intervention, which was implemented to systematically reinforce cocaine abstinence. In addition to previous CCTA (preintervention), CCTA was performed at the intervention baseline and at postintervention. Plaque analyses were performed to determine the trajectory of plaque changes in the absence of intervention by comparing the preintervention ...
Pairs of spouses share common lifestyle factors. In a cross-sectional analysis, we investigated w... more Pairs of spouses share common lifestyle factors. In a cross-sectional analysis, we investigated whether spouses of diabetic individuals had a higher prevalence of diabetes and cardiometabolic disorders in a community-based population of Chinese adults aged 40 years or older between 2011 and 2012. A total of 34,805 pairs of spouses were identified. All participants underwent a standard oral glucose tolerance test and provided detailed clinical, sociodemographic, and lifestyle information. Diabetes and multiple cardiometabolic disorders were defined according to standard criteria. Compared with participants whose spouses did not have diabetes, participants whose spouses had diabetes had higher odds of having diabetes (for men, odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.22, 1.45; for women, OR = 1.35, 95% CI: 1.24, 1.47), obesity (for men, OR = 1.34, 95% CI: 1.13, 1.59; for women, OR = 1.19, 95% CI: 1.05, 1.35), metabolic syndrome (for men, OR = 1.31, 95% CI: 1.21, 1.42; f...
Reduced rates of adenosine triphosphate synthesis through myocardial creatine kinase (CK flux) pr... more Reduced rates of adenosine triphosphate synthesis through myocardial creatine kinase (CK flux) predict adverse clinical events in patients with heart failure.
Background— Myocardial ischemia is an important determinant of regional left ventricular systolic... more Background— Myocardial ischemia is an important determinant of regional left ventricular systolic function. Myocardial blood flow reserve may be impaired by cardiovascular disease before alterations of myocardial perfusion at rest become manifest. Nevertheless, the relation between flow reserve and regional myocardial function has not been studied in individuals without a history of clinical heart disease. Methods and Results— Seventy-four participants (66±9 years, mean±SD) of the Multi-Ethnic Study of Atherosclerosis (MESA) underwent myocardial magnetic resonance tagging and contrast-enhanced perfusion studies. Regional myocardial function was evaluated as peak systolic circumferential strain (Ecc) in the three main coronary territories (left anterior descending [LAD], left circumflex, and right coronary artery [RCA]). Myocardial blood flow at rest and during adenosine-induced hyperemia was quantified by contrast-enhanced magnetic resonance imaging, to study the relation between re...
Background— Cardiosphere-derived cells (CDCs) isolated from human endomyocardial biopsies reduce ... more Background— Cardiosphere-derived cells (CDCs) isolated from human endomyocardial biopsies reduce infarct size and improve cardiac function in mice. Safety and efficacy testing in large animals is necessary for clinical translation. Methods and Results— Mesenchymal stem cells, which resemble CDCs in size and thrombogenicity, have been associated with infarction after intracoronary infusion. To maximize CDC engraftment while avoiding infarction, we optimized the infusion protocol in 19 healthy pigs. A modified cocktail of CDCs in calcium-free PBS, 100 U/mL of heparin, and 250 μg/mL of nitroglycerin eliminated infusion-related infarction. Subsequent infusion experiments in 17 pigs with postinfarct left ventricular dysfunction showed CDC doses ≥10 7 but <2.5×10 7 result in new myocardial tissue formation without infarction. In a pivotal randomized study, 7 infarcted pigs received 300 000 CDCs/kg (≈10 7 total) and 7 received placebo (vehicle alone). Cardiac magnetic resonance imaging ...
Aims Lipoprotein(a) [Lp(a)] levels are generally constant throughout an individual’s lifetime, an... more Aims Lipoprotein(a) [Lp(a)] levels are generally constant throughout an individual’s lifetime, and current guidelines recommend that a single measurement is sufficient to assess the risk of coronary artery disease (CAD). However, it is unclear whether a single measurement of Lp(a) in individuals with acute myocardial infarction (MI) is indicative of the Lp(a) level six months following the event. Methods and results Lp(a) levels were obtained from individuals with non–ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI) (n = 99) within 24 h of hospital admission and after six months, who were enrolled in two randomized trials of evolocumab and placebo, and in individuals with NSTEMI or STEMI (n = 9) who enrolled in a small observation arm of the two protocols and did not receive study drug, but whose levels were obtained at the same time points. Median Lp(a) levels increased from 53.5 nmol/L (19, 165) during hospital admission to 58.0 nmol/L (14....
Our objective was to assess whether human immunodeficiency virus (HIV)-infection directly or indi... more Our objective was to assess whether human immunodeficiency virus (HIV)-infection directly or indirectly promotes the progression of clinical characteristics of coronary artery disease (CAD). 300 African Americans with asymptomatic CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV-infected) who underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years) were randomly selected from 1429 participants of a prospective epidemiological study between May 2004 and August 2015. We calculated Agatston-scores, number of coronary plaques and segment stenosis score (SSS). Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use on CAD. There was no significant difference in annual progression rates between HIV-infected and—uninfected regarding Agatston-scores (10.8 ± 25.1/year vs. 7.2 ± 17.8/year, p = 0.17), the number of plaques (0.2 ± 0.3/year vs. 0.3 ± 0.5/year, p = 0.11) or SSS (0.5 ...
Background/Introduction Cross-sectional studies are inconsistent on the potential independent adv... more Background/Introduction Cross-sectional studies are inconsistent on the potential independent adverse effects of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD). Furthermore, there is no information on the potential effects of HIV-infection on plaque volumes. Also, only the independent effects of HIV-infection on CAD have been investigated. Purpose In a prospective longitudinal observational cohort, we wished to assess whether HIV-infection accelerates CAD independently, or by acting in synergistic fashion with conventional and nonconventional cardiovascular risk factors to accelerate disease progression as assessed by clinical and volumetric parameters of CAD on coronary CT angiography (CCTA). Methods Overall, 300 asymptomatic individuals without cardiovascular symptoms but with CCTA-confirmed coronary plaques (210 males, age: 48.0±7.2 years) with or without HIV (226 HIV-infected) prospectively underwent CCTA at two time points (mean follow-up: 4.0±2.3...
Progress in neuro-psychopharmacology & biological psychiatry, Jan 2, 2018
Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individua... more Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individuals on antiretroviral therapy (ART), and that HIV itself may accelerate aging, the issue of whether cocaine use plays a role in HIV-associated aging in HIV-infected cocaine users has not been reported. The goals of this study were (1) to explore factor(s) associated with peripheral blood leukocyte telomere length, a marker of cellular replicative history, and telomere shortening in HIV-infected individuals, and (2) to assess whether cocaine use plays a role in accelerating telomere shortening in cocaine users with HIV infection. Between June 2010 and December 2016, 147 HIV-infected participants in Baltimore, Maryland, were enrolled in a cross-sectional study investigating factor(s) associated with telomere length. Of these 147, 93 participated in a follow-up study to examine factor(s) associated with telomere shortening. Robust regression model was used to analyze cross-sectional data and...
HIV+ individuals experience an increased burden of coronary artery disease (CAD) not adequately a... more HIV+ individuals experience an increased burden of coronary artery disease (CAD) not adequately accounted for by traditional CAD risk factors. Coronary endothelial function (CEF), a barometer of vascular health, is depressed early in atherosclerosis and predicts future events but has not been studied in HIV+ individuals. We tested whether CEF is impaired in HIV+ subjects without CAD as compared to an HIV- population matched for cardiac risk factors. In this observational study, CEF was measured noninvasively by quantifying isometric handgrip exercise (IHE)-induced changes in coronary vasoreactivity with MRI in 18 participants with HIV but no CAD (HIV+CAD-, based on prior imaging), 36 age- and cardiac risk factor-matched healthy participants with neither HIV nor CAD (HIV-CAD-), 41 subjects with no HIV but with known CAD (HIV-CAD+) and 17 subjects with both HIV and CAD (HIV+CAD+). CEF was significantly depressed in HIV+CAD- subjects as compared to that of risk-factor-matched HIV-CAD- ...
Although rapid progression of coronary atherosclerosis was observed in chronic cocaine users, it ... more Although rapid progression of coronary atherosclerosis was observed in chronic cocaine users, it is unknown whether reduced cocaine use retards the progression of atherosclerosis. We investigated whether reduced cocaine use over a 12-month period was associated with coronary plaque regression in cocaine users. Fifteen African American chronic cocaine users with previously coronary computed tomography angiography (CCTA)-confirmed >50% coronary stenosis in Baltimore, Maryland, were enrolled in a study to investigate whether reduced cocaine use is associated with changes in coronary plaque burden over a 12-month period of cash-based incentive intervention, which was implemented to systematically reinforce cocaine abstinence. In addition to previous CCTA (preintervention), CCTA was performed at the intervention baseline and at postintervention. Plaque analyses were performed to determine the trajectory of plaque changes in the absence of intervention by comparing the preintervention ...
Pairs of spouses share common lifestyle factors. In a cross-sectional analysis, we investigated w... more Pairs of spouses share common lifestyle factors. In a cross-sectional analysis, we investigated whether spouses of diabetic individuals had a higher prevalence of diabetes and cardiometabolic disorders in a community-based population of Chinese adults aged 40 years or older between 2011 and 2012. A total of 34,805 pairs of spouses were identified. All participants underwent a standard oral glucose tolerance test and provided detailed clinical, sociodemographic, and lifestyle information. Diabetes and multiple cardiometabolic disorders were defined according to standard criteria. Compared with participants whose spouses did not have diabetes, participants whose spouses had diabetes had higher odds of having diabetes (for men, odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.22, 1.45; for women, OR = 1.35, 95% CI: 1.24, 1.47), obesity (for men, OR = 1.34, 95% CI: 1.13, 1.59; for women, OR = 1.19, 95% CI: 1.05, 1.35), metabolic syndrome (for men, OR = 1.31, 95% CI: 1.21, 1.42; f...
Reduced rates of adenosine triphosphate synthesis through myocardial creatine kinase (CK flux) pr... more Reduced rates of adenosine triphosphate synthesis through myocardial creatine kinase (CK flux) predict adverse clinical events in patients with heart failure.
Background— Myocardial ischemia is an important determinant of regional left ventricular systolic... more Background— Myocardial ischemia is an important determinant of regional left ventricular systolic function. Myocardial blood flow reserve may be impaired by cardiovascular disease before alterations of myocardial perfusion at rest become manifest. Nevertheless, the relation between flow reserve and regional myocardial function has not been studied in individuals without a history of clinical heart disease. Methods and Results— Seventy-four participants (66±9 years, mean±SD) of the Multi-Ethnic Study of Atherosclerosis (MESA) underwent myocardial magnetic resonance tagging and contrast-enhanced perfusion studies. Regional myocardial function was evaluated as peak systolic circumferential strain (Ecc) in the three main coronary territories (left anterior descending [LAD], left circumflex, and right coronary artery [RCA]). Myocardial blood flow at rest and during adenosine-induced hyperemia was quantified by contrast-enhanced magnetic resonance imaging, to study the relation between re...
Background— Cardiosphere-derived cells (CDCs) isolated from human endomyocardial biopsies reduce ... more Background— Cardiosphere-derived cells (CDCs) isolated from human endomyocardial biopsies reduce infarct size and improve cardiac function in mice. Safety and efficacy testing in large animals is necessary for clinical translation. Methods and Results— Mesenchymal stem cells, which resemble CDCs in size and thrombogenicity, have been associated with infarction after intracoronary infusion. To maximize CDC engraftment while avoiding infarction, we optimized the infusion protocol in 19 healthy pigs. A modified cocktail of CDCs in calcium-free PBS, 100 U/mL of heparin, and 250 μg/mL of nitroglycerin eliminated infusion-related infarction. Subsequent infusion experiments in 17 pigs with postinfarct left ventricular dysfunction showed CDC doses ≥10 7 but <2.5×10 7 result in new myocardial tissue formation without infarction. In a pivotal randomized study, 7 infarcted pigs received 300 000 CDCs/kg (≈10 7 total) and 7 received placebo (vehicle alone). Cardiac magnetic resonance imaging ...
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