Arterial stiffness predicts cardiovascular events beyond traditional risk factors. However, the relationship with aging of novel noninvasive measures of aortic function by MRI and their ...interrelationship with established markers of vascular stiffness remain unclear and currently limit their potential impact. Our aim was to compare age-related changes of central measures of aortic function with carotid distensibility, global carotid–femoral pulse wave velocity, and wave reflections. We determined aortic strain, distensibility, and aortic arch pulse wave velocity by MRI, carotid distensibility by ultrasound, and carotid–femoral pulse wave velocity by tonometry in 111 asymptomatic subjects (54 men, age range20 to 84 years). Central pressures were used to calculate aortic distensibility. Peripheral and central pulse pressure, augmentation index, and carotid–femoral pulse wave velocity increased with age, but aortic strain and aortic arch PWV were most closely and specifically related to aging. Ascending aortic (AA) strain and distensibility decreased, respectively, by 5.3±0.5% (R=0.54, P<0.0001) and 13.6±1 kPa×10 (R=0.62, P<0.0001), and aortic arch pulse wave velocity increased by 1.6±0.13 m/sec (R=0.60, P<0.0001) for each decade of age after adjustment for gender, body size, and heart rate. We demonstrate in this study a dramatic decrease in AA distensibility before the fifth decade of life in individuals with diverse prevalence of risk factors free of overt cardiovascular disease. In particular, compared with other measures of aortic function, the best markers of subclinical large artery stiffening, were AA distensibility in younger and aortic arch pulse wave velocity in older individuals.
BACKGROUND:Although small elevations of high-sensitive cardiac troponin T (hs-cTnT) are associated with incident heart failure (HF) in the general population, the underlying mechanisms are not well ...defined. Evaluating the association of hs-cTnT with replacement fibrosis and progression of structural heart disease before symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy.
METHODS:We measured hs-cTnT at baseline among 4986 participants in MESA (Multi-Ethnic Study of Atherosclerosis), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance imaging was performed at baseline. Repeat cardiac magnetic resonance was performed 10 years later among 2831 participants who remained free of interim CVD events; of these, 1723 received gadolinium-enhanced cardiac magnetic resonance for characterization of replacement fibrosis by late gadolinium enhancement. Progression of subclinical CVD was defined by 10-year change in left ventricular structure and function. Associations of hs-cTnT with incident HF, CV-related mortality, and coronary heart disease were estimated using Cox regression models.
RESULTS:Late gadolinium enhancement for replacement fibrosis was detectable in 6.3% participants without interim CVD events by follow-up cardiac magnetic resonance. A graded association was observed between higher baseline hs-cTnT categories and late gadolinium enhancement (≥7.42 ng/L versus <limit of detection <3 ng/L; adjusted odds ratio, 2.87; 95% confidence interval, 1.38–5.94). Higher hs-cTnT was also associated with a greater probability of an increase in LV mass >12% (highest category versus <limit of detection; odds ratio, 1.50; 95% confidence interval, 1.09–2.07), but not with decline in left ventricular ejection fraction. The risk of incident HF was greater for higher hs-cTnT (≥8.81 ng/L versus <limit of detection; adjusted hazards ratio, 5.59; 95% CI, 2.97–10.68).
CONCLUSIONS:hs-cTnT levels are associated with replacement fibrosis and progressive changes in left ventricular structure in CVD-free adults, findings that may precede HF symptoms by years. Minor elevations of hs-cTnT may represent a biochemical signature of early subclinical cardiac disease, providing an opportunity for targeted preventive interventions.
Multidetector Computed Tomography Myocardial Perfusion Imaging During Adenosine Stress
Richard T. George, Caterina Silva, Marco A. S. Cordeiro, Anthony DiPaula, Douglas R. Thompson, William F. ...McCarthy, Takashi Ichihara, Joao A. C. Lima, Albert C. Lardo
This study investigates the feasibility of myocardial perfusion imaging (MPI) using helical multidetector computed tomography (MDCT) in a canine model of left anterior descending artery stenosis. Results indicate that adenosine-augmented MDCT MPI can be performed in a single scan during first-pass contrast-enhancement, and MDCT myocardial signal density ratio correlates well with microsphere-derived myocardial blood flow. The ability to perform MPI during first-pass contrast-enhanced MDCT imaging could have significant implications in the diagnosis and treatment of coronary artery disease.
The purpose of this study is to validate the accuracy of multidetector computed tomography (MDCT) to measure differences in regional myocardial perfusion during adenosine stress in a canine model of left anterior descending (LAD) artery stenosis, during first-pass, contrast-enhanced helical MDCT.
Myocardial perfusion imaging by MDCT may have significant implications in the diagnosis and treatment of coronary artery disease.
Eight dogs were prepared with a LAD stenosis, and contrast-enhanced MDCT imaging was performed 5 min into adenosine infusion (0.14 to 0.21 mg/kg/min). Images were analyzed using a semiautomated approach to define the regional signal density (SD) ratio (myocardial SD/left ventricular blood pool SD) in stenosed and remote territories, and then compared with microsphere myocardial blood flow (MBF) measurements.
Mean MBF in stenosed versus remote territories was 1.37 ± 0.46 ml/g/min and 1.29 ± 0.48 ml/g/min at baseline (p = NS) and 2.54 ± 0.93 ml/g/min and 8.94 ± 5.74 ml/g/min during adenosine infusion, respectively (p < 0.05). Myocardial SD was 92.3 ± 39.5 HU in stenosed versus 180.4 ± 41.9 HU in remote territories (p < 0.001). There was a significant linear association of the SD ratio with MBF in the stenosed territory (R = 0.98, p = 0.001) and between regional myocardial SD ratio and MBF <8 ml/g/min, slope = 0.035, SE = 0.007, p < 0.0001. Overall, there was a significant non-linear relationship over the range of flows studied (LR chi-square 2 degrees of freedom = 31.8, p < 0.0001).
Adenosine-augmented MDCT myocardial perfusion imaging provides semiquantitative measurements of myocardial perfusion during first-pass MDCT imaging in a canine model of LAD stenosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Aims
While coronary artery calcium (CAC) has been extensively validated for predicting clinical events, most outcome studies of CAC have evaluated coronary heart disease (CHD) rather than ...atherosclerotic cardiovascular disease (ASCVD) events (including stroke). Also, virtually all CAC studies are of short- or intermediate-term follow-up, so studies across multi-ethnic cohorts with long-term follow-up are warranted prior to widespread clinical use. We sought to evaluate the contribution of CAC using the population-based MESA cohort with over 10 years of follow-up for ASCVD events, and whether the association of CAC with events varied by sex, race/ethnicity, or age category.
Methods and results
We utilized MESA, a prospective multi-ethnic cohort study of 6814 participants (51% women), aged 45–84 years, free of clinical CVD at baseline. We evaluated the relationship between CAC and incident ASCVD using Cox regression models adjusted for age, race/ethnicity, sex, education, income, cigarette smoking status, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes, lipid-lowering medication, systolic blood pressure, antihypertensive medication, intentional physical exercise, and body mass index. Only the first event for each individual was used in the analysis. Overall, 500 incident ASCVD (7.4%) events were observed in the total study population over a median of 11.1 years. Hard ASCVD included 217 myocardial infarction, 188 strokes (not transient ischaemic attack), 13 resuscitated cardiac arrest, and 82 CHD deaths. Event rates in those with CAC = 0 Agatston units ranged from 1.3% to 5.6%, while for those with CAC > 300, the 10-year event rates ranged from 13.1% to 25.6% across different age, gender, and racial subgroups. At 10 years of follow-up, all participants with CAC > 100 were estimated to have >7.5% risk regardless of demographic subset. Ten-year ASCVD event rates increased steadily across CAC categories regardless of age, sex, or race/ethnicity. For each doubling of CAC, we estimated a 14% relative increment in ASCVD risk, holding all other risk factors constant. This association was not significantly modified by age, sex, race/ethnicity, or baseline lipid-lowering use.
Conclusions
Coronary artery calcium is associated strongly and in a graded fashion with 10-year risk of incident ASCVD as it is for CHD, independent of standard risk factors, and similarly by age, gender, and ethnicity. While 10-year event rates in those with CAC = 0 were almost exclusively below 5%, those with CAC ≥ 100 were consistently above 7.5%, making these potentially valuable cutpoints for the consideration of preventive therapies. Coronary artery calcium strongly predicts risk with the same magnitude of effect in all races, age groups, and both sexes, which makes it among the most useful markers for predicting ASCVD risk.
We sought to assess the impact of smoking status, cumulative pack-years, and time since cessation (the latter in former smokers only) on 3 important domains of cardiovascular disease: inflammation, ...vascular dynamics and function, and subclinical atherosclerosis.
The Multi-Ethnic Study of Atherosclerosis (MESA) cohort enrolled 6814 adults without prior cardiovascular disease. Smoking variables were determined by self-report and confirmed with urinary cotinine. We examined cross-sectional associations between smoking parameters and (1) inflammatory biomarkers (high-sensitivity C-reactive protein hsCRP, interleukin-6, and fibrinogen); (2) vascular dynamics and function (brachial flow-mediated dilation and carotid distensibility by ultrasound, as well as aortic distensibility by MRI); and (3) subclinical atherosclerosis (coronary artery calcification, carotid intima-media thickness, and ankle-brachial index). We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Mean age was 62 years and 47% were male. There was no consistent association between smoking and vascular distensibility or flow-mediated dilation outcomes. However, compared with never smokers, the adjusted association between current smoking and measures of either inflammation or subclinical atherosclerosis was consistently stronger than for former smoking (eg, odds ratio for hsCRP>2 mg/L of 1.7 95% confidence interval, 1.5-2.1 versus 1.2 1.1-1.4, odds ratio for coronary artery calcification>0 of 1.8 1.5-2.1 versus 1.4 1.2-1.6, respectively). Similar associations were seen for interleukin-6, fibrinogen, carotid intima-media thickness, and ankle-brachial index. A monotonic association was also found between higher pack-year quartiles and increasing inflammatory markers. Furthermore, current smokers with hsCRP>2 mg/L were more likely to have increased carotid intima-media thickness, abnormal ankle-brachial index, and coronary artery calcification>75th percentile for age, sex, and race (relative to smokers with hsCRP<2 mg/L, interaction P<0.05 for all 3 outcomes). In contrast, time since quitting in former smokers was independently associated with lower inflammation and atherosclerosis (eg, odds ratio for hsCRP>2 mg/L of 0.91 0.88-0.95 and odds ratio for coronary artery calcification>0 of 0.94 0.90-0.97 for every 5-year cessation interval).
These findings expand our understanding of the harmful effects of smoking and help explain the cardiovascular benefits of smoking cessation.
Background Elevated coronary artery calcium (CAC) is a marker for increase risk of coronary heart disease (CHD). Although most CHD events occur among individuals with advanced CAC, CHD can also occur ...in individuals with little or no calcified plaque. In this study, we sought to evaluate the characteristics associated with incident CHD events in the setting of minimal (score ≤10) or absent CAC (score of zero). Methods Asymptomatic participants in the MESA (N = 6,809) were followed for occurrence of all CHD events (including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death) and hard CHD events (myocardial infarction or CHD death). Time to incident CHD was modeled using age-and gender-adjusted Cox regression. Results The final study population consisted of 3,923 MESA asymptomatic participants (mean age 58 ± 9 years, 39% males) who had CAC scores of 0 to 10. Overall, no detectable CAC was seen in 3415 individuals, whereas 508 had CAC scores of 1 to 10. During follow-up (median 4.1 years), there were 16 incident hard events and 28 all CHD events in individuals with absent or minimal CAC. In age-, gender-, race-, and CHD risk factor-adjusted analysis, minimal CAC (1-10) was associated with an estimated 3-fold greater risk of a hard CHD event (HR 3.23, 95% CI 1.17-8.95) or of all CHD event (HR 3.66, 95% CI 1.71-7.85) compared to those with CAC = 0. Former smoking (HR 3.57, 95% CI 1.08-11.77), current smoking (HR 4.93, 95% CI 1.20-20.30), and diabetes (HR 3.09, 95% CI 1.07-8.93) were significant risk factors for events in those with CAC = 0. Conclusion Asymptomatic persons with absent or minimal CAC are at very low risk of future cardiovascular events. Individuals with minimal CAC (1-10) were significantly increased to 3-fold increased risk for incident CHD events relative to those with CAC scores of zero.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background The presence and extent of coronary artery calcium (CAC) is an independent predictor of coronary heart disease (CHD) morbidity and mortality. Few studies have evaluated ...interactions or independent incremental risk for coronary and thoracic aortic calcification (TAC). The independent predictive value of TAC for CHD events is not well-established. Methods This study used risk factor and computed tomography scan data from 6807 participants in the multi-ethnic study of atherosclerosis (MESA). Using the same images for each participant, TAC and CAC were each computed using the Agatston method. The study subjects were free of incident CHD at entry into the study. Results The mean age of the study population ( n = 6807) was 62 ± 10 years (47% males). At baseline, the prevalence of TAC and CAC was 28% (1904/6809) and 50% (3393/6809), respectively. Over 4.5 ± 0.9 years, a total of 232 participants (3.41%) had CHD events, of which 132 (1.94%) had a hard event (myocardial infarction, resuscitated cardiac arrest, or CHD death). There was a significant interaction between gender and TAC for CHD events ( p < 0.05). Specifically, in women, the risk of all CHD event was nearly 3-fold greater among those with any TAC (hazard ratio: 3.04, 95% CI: 1.60–5.76). After further adjustment for increasing CAC score, this risk was attenuated but remained robust (HR: 2.15, 95% CI: 1.10–4.17). Conversely, there was no significant association between TAC and incident CHD in men. In women, the likelihood ratio chi square statistics indicate that the addition of TAC contributed significantly to predicting incident CHD event above that provided by traditional risk factors alone (chi square = 12.44, p = 0.0004) as well as risk factors + CAC scores (chi square = 5.33, p = 0.02). On the other hand, addition of TAC only contributed in the prediction of hard CHD events to traditional risk factors (chi-square = 4.33, p = 0.04) in women, without contributing to the model containing both risk factors and CAC scores (chi square = 1.55, p = 0.21). Conclusion Our study indicates that TAC is a significant predictor of future coronary events only in women, independent of CAC. On studies obtained for either cardiac or lung applications, determination of TAC may provide modest supplementary prognostic information in women with no extra cost or radiation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In a population-based study, emphysema was quantified by computed tomography, pulmonary function was assessed by spirometry, and cardiac volumes and function were measured by magnetic resonance ...imaging. Both percent emphysema and the severity of airflow obstruction were linearly related to reductions in left ventricular end-diastolic volume, stroke volume, and cardiac output. These effects were more pronounced among smokers.
In a population-based study, emphysema and the severity of airflow obstruction were linearly related to reductions in left ventricular end-diastolic volume, stroke volume, and cardiac output.
Chronic obstructive pulmonary disease (COPD), defined as airflow obstruction that is not fully reversible,
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is currently the fourth leading cause of death in the United States.
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COPD overlaps partially with emphysema, which is characterized by the destruction of alveolar walls and the permanent enlargement of air spaces distal to the terminal bronchioles.
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,
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Cor pulmonale, which can occur in very severe COPD, is characterized by elevated pulmonary vascular resistance and right heart failure, with associated reductions in left ventricular filling, left ventricular stroke volume, and cardiac output, although left ventricular ejection fraction is generally preserved.
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This disorder may occur . . .
Elevated D-dimer levels on admission predict prognosis in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), but the ...association of D-dimer levels with structural markers of myocardial injury in these patients is unknown.
We performed cardiac magnetic resonance (CMR) imaging in 208 patients treated with primary PCI for STEMI. CMR was performed a median of 3 days after the index procedure. Of the 208 patients studied, 75 patients had D-dimer levels above the normal range on admission (>0.5 μg/mL; high D-dimer group) while 133 had normal levels (≤0.5 μg/mL; low D-dimer group). The primary outcome was myocardial infarct size assessed by CMR. Secondary outcomes included area at risk (AAR), microvascular obstruction (MVO) area, and myocardial salvage index (MSI).
In CMR analysis, myocardial infarct size was larger in the high D-dimer group than in the low D-dimer group (22.3% 16.2-30.5 versus 18.8% 10.7-26.7; p = 0.02). Compared to the low D-dimer group, the high D-dimer group also had a larger AAR (38.1% 31.7-46.9 versus 35.8% 24.2-45.3; p = 0.04) and a smaller MSI (37.7 28.2-46.9 versus 47.1 33.2-57.0; p = 0.01). In multivariate analysis, high D-dimer levels were significantly associated with larger myocardial infarct (OR 2.59; 95% CI 1.37-4.87; p<0.01) and lower MSI (OR 2.62; 95% CI 1.44-4.78; p<0.01).
In STEMI patients undergoing primary PCI, high D-dimer levels on admission were associated with a larger myocardial infarct size, a greater extent of AAR, and lower MSI, as assessed by CMR data. Elevated initial D-dimer level may be a marker of advanced myocardial injury in patients treated with primary PCI for STEMI.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
RATIONALE:Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies.
OBJECTIVE:To test the ability of random survival ...forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores.
METHODS AND RESULTS:We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%–25%).
CONCLUSIONS:Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality.
CLINICAL TRIAL REGISTRATION:URLhttp://www.clinicaltrials.gov. Unique identifierNCT00005487.
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