Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance Heralds an Adverse Prognosis in Nonischemic Cardiomyopathy Katherine C. Wu, Robert G. Weiss, David R. Thiemann, Kakuya Kitagawa, André ...Schmidt, Darshan Dalal, Shenghan Lai, David A. Bluemke, Gary Gerstenblith, Eduardo Marbán, Gordon F. Tomaselli, João A. C. Lima Predicting prognosis in nonischemic cardiomyopathy patients is challenging, and current risk stratification approaches are limited. Cardiovascular magnetic resonance (CMR) detects myocardial fibrosis, which appears as late gadolinium enhancement (LGE). The presence of LGE predicts an 8-fold increased risk of an adverse cardiac outcome (hazard ratio 8.2, 95% confidence interval 2.2 to 30.9; p = 0.002), after controlling for baseline variables. A CMR LGE may reflect the transition from compensated to decompensated state resulting from long-term stressors such as sustained adrenergic activation and/or the mechanical disadvantages caused by left ventricular remodeling leading to increasing fibrosis. Identifying CMR LGE may significantly improve risk stratification strategies in this high-risk population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, was associated with subclinical atherosclerosis in many cross-sectional studies, but the prospective ...association between NAFLD and the progression of atherosclerosis has not been evaluated. This study was conducted to evaluate the association between NAFLD and the progression of coronary atherosclerosis.
This retrospective cohort study included 4731 adult men and women with no history of cardiovascular disease (CVD), liver disease or cancer at baseline who participated in a repeated regular health screening examination between 2004 and 2013. Fatty liver was diagnosed by ultrasound based on standard criteria, including parenchymal brightness, liver-to-kidney contrast, deep beam attenuation and bright vessel walls. Progression of coronary artery calcium (CAC) scores was measured using multidetector CT scanners.
The average duration of follow-up was 3.9 years. During follow-up, the annual rate of CAC progression in participants with and without NAFLD were 22% (95% CI 20% to 23%) and 17% (16% to 18%), respectively (p<0.001). The multivariable ratio of progression rates comparing participants with NAFLD with those without NAFLD was 1.04 (1.02 to 1.05; p<0.001). The association between NAFLD and CAC progression was similar in most subgroups analysed, including in participants with CAC 0 and in those with CAC >0 at baseline.
In this large cohort study of adult men and women with no history of CVD, NAFLD was significantly associated with the development of CAC independent of cardiovascular and metabolic risk factors. NAFLD may play a pathophysiological role in atherosclerosis development and may be useful to identify subjects with a higher risk of subclinical disease progression.
Cardiovascular disease (CVD) and cancer continue to be the 2 leading causes of death in developed countries despite significant improvements in the prevention, screening, and treatment of both ...diseases. They remain significant public health problems, growing in importance globally. Despite this threat, the fields of cardiology and oncology have been relatively disconnected. With many shared modifiable risk factors, cancer and CVD often coexist in the same individuals; those diagnosed with lung cancer, breast cancer, and colon cancer are at higher risk of CVD, and those with CVD are at higher risk of developing many types of common cancers. Screening paradigms have been established in parallel, but there are opportunities for combined risk assessments for cancer and CVD risk. Joining forces for combined cardiovascular and hemato-oncological preventive and research efforts will likely have synergistic, worldwide public health benefits.
The risk of atherosclerotic cardiovascular disease (ASCVD) at currently defined normal systolic blood pressure (SBP) levels in persons without ASCVD risk factors based on current definitions is not ...well defined.
To examine the association of SBP levels with coronary artery calcium and ASCVD in persons without hypertension or other traditional ASCVD risk factors based on current definitions.
A cohort of 1457 participants free of ASCVD from the Multi-Ethnic Study of Atherosclerosis who were without dyslipidemia (low-density lipoprotein cholesterol level ≥160 mg/dL or high-density lipoprotein cholesterol level <40 mg/dL), diabetes (fasting glucose level ≥126 mg/dL), treatment for hyperlipidemia or diabetes, or current tobacco use, and had an SBP level between 90 and 129 mm Hg. Participants receiving hypertension medication were excluded. Coronary artery calcium was classified as absent or present and adjusted hazard ratios (aHRs) were calculated for incident ASCVD. The study was conducted from March 27, 2018, to February 12, 2020.
Systolic blood pressure.
Presence or absence of coronary artery calcium and incident ASCVD events.
Of the 1457 participants, 894 were women (61.4%); mean (SD) age was 58.1 (9.8) years and mean (SD) follow-up was 14.5 (3.9) years. There was an increase in traditional ASCVD risk factors, coronary artery calcium, and incident ASCVD events with increasing SBP levels. The aHR for ASCVD was 1.53 (95% CI, 1.17-1.99) for every 10-mm Hg increase in SBP levels. Compared with persons with SBP levels 90 to 99 mm Hg, the aHR for ASCVD risk was 3.00 (95% CI, 1.01-8.88) for SBP levels 100 to 109 mm Hg, 3.10 (95% CI, 1.03-9.28) for SBP levels 110 to 119 mm Hg, and 4.58 (95% CI, 1.47-14.27) for SBP levels 120 to 129 mm Hg.
Beginning at an SBP level as low as 90 mm Hg, there appears to be a stepwise increase in the presence of coronary artery calcium and the risk of incident ASCVD with increasing SBP levels. These results highlight the importance of primordial prevention for SBP level increase and other traditional ASCVD risk factors, which generally seem to have similar trajectories of graded increase in risk within values traditionally considered to be normal.
Understanding the relationship of cardiovascular structure and function to age is confounded by the high prevalence of traditional risk factors in the United States. The purpose of the study is to ...compare left ventricular (LV) and aortic structural, and functional parameters in individuals with and without traditional risk factors in a population-based cohort.
3015 study participants (48% men, age 55-94, mean 69.01±9.17 years) in the Multi-Ethnic Study of Atherosclerosis (MESA) underwent cardiovascular magnetic resonance (CMR) imaging from 2010-2012. Absence of cardiovascular (CV) risk factors (no hypertension, diabetes or impaired fasting glucose, obesity, smoking or hypercholesterolemia) was infrequent, occurring in just 314 (10.4%, 38% men) of 3015 participants. In multivariable analyses adjusting for age, sex and race, individuals with CV risk factors had significantly larger LV mass index (by 17%) and lower LV contractibility (circumference strain, lower by 14%). Indexed LV volumes and stroke volume were inversely associated with age, but such relationships were not statistically significant in risk-free male subjects (p>0.05). Men with CV risk factors showed positive association of CMR T1 indices of myocardial fibrosis with age. Aortic function was similar in individuals with and without risk factors; age was associated with decline of aortic function in both CV and no CV risk factor groups.
Our results support that LV structure and function are better preserved in senescent hearts in the absence of traditional cardiovascular risk factors, and such protection is more prominent in men than in women.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Myocardial interstitial fibrosis is part of the advanced disease stage of most cardiovascular pathologies. It has been characterized histologically in various disease settings from hypertensive heart ...disease and diabetic cardiomyopathy to severe aortic stenosis. It is also involved in the process of aging. In cardiovascular medicine, myocardial interstitial fibrosis is associated with several adverse outcomes, especially heart failure (HF) and sudden cardiac death. Until recently, clinical measures of interstitial fibrosis could only be made by invasive myocardial biopsy. The availability of cardiac magnetic resonance (CMR) T1 mapping techniques allows for the indirect measurement of interstitial space characteristics and extracellular volume size, which is closely correlated with collagen content and interstitial infiltration by amyloid and other molecules. There has been significant improvement in the accuracy and reproducibility of T1 acquisition sequences in the last decade; however, the correct use of this technique requires a solid CMR expertise in daily imaging practice. CMR has become the gold standard to assess left ventricular (LV) remodeling and functional features associated with interstitial fibrosis. These features can be detected in the early stages of HF. The main objective of this paper is to review the relevant results of preclinical and clinical observational studies that demonstrate the prognostic impact of interstitial fibrosis assessed by T1 mapping, as well as adverse left ventricular remodeling, as determinants of HF. Therefore, this review focuses on the pathological mechanisms underlying LV remodeling and interstitial fibrosis, in addition to the technical considerations involved in the assessment of interstitial LV fibrosis by CMR. It provides a thorough review of clinical evidence that demonstrates the association of interstitial fibrosis and other-CMR derived LV phenotypes with Stages A and B HF.
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•The myocardium undergoes important tissue composition (hypertrophy, interstitial and replacement fibrosis, and so on) and remodeling changes in Stage A and B HF.•CMR offers a comprehensive and reproducible assessment of LV tissue and anatomy modifications, with the potential to monitor different phenotypes in Stage A and B HF.•T1 mapping and ECV assessment by CMR requires careful acquisition protocol and solid expertise for routine practice.•Clinical use of these CMR measurements for therapeutic management still requires randomized controlled clinical trials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IMPORTANCE: Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less ...clear. OBJECTIVE: To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD). DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up. MAIN OUTCOMES AND MEASURES: The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated. RESULTS: Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio HR, 0.85; 95% CI, 0.80-0.91; P < .001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P = .002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (β = −0.24; 95% CI, −0.45 to −0.03; P = .02) and significantly better lobal longitudinal strain (β = −0.09; 95% CI, −0.14 to −0.05; P < .001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P = .002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P = .006), respectively, along with a more impaired strain (β = 0.15; 95% CI, 0.08-0.23; P < .001). No association between change in fitness and CAC was found. CONCLUSIONS AND RELEVANCE: Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.
Emerging research indicates that high HDL-C levels might not be cardioprotective, potentially worsening cardiovascular disease (CVD) outcomes. Yet, there is no data on HDL-C's association with other ...CVD risk factors like myocardial fibrosis, a key aspect of cardiac remodeling predicting negative outcomes. We therefore aimed to study the association between HDL-C levels with interstitial myocardial fibrosis (IMF) and myocardial scar measured by CMR T1-mapping and late-gadolinium enhancement (LGE), respectively. There were 1863 participants (mean age of 69 years) who had both serum HDL-C measurements and underwent CMR. Analysis was done among those with available indices of interstitial fibrosis (extracellular volume fraction ECV; N = 1172 and native-T1; N = 1863) and replacement fibrosis by LGE (N = 1172). HDL-C was analyzed as both logarithmically-transformed and categorized into < 40 (low),40-59 (normal), and ≥ 60mg/dL (high). Multivariable linear and logistic regression models were constructed to assess the associations of HDL-C with CMR-obtained measures of IMF, ECV% and native-T1 time, and myocardial scar, respectively. In the fully adjusted model, each 1-SD increment of log HDL-C was associated with a 1% increment in ECV% (p = 0.01) and an 18-ms increment in native-T1 (p < 0.001). When stratified by HDL-C categories, those with high HDL-C (≥ 60mg/dL) had significantly higher ECV (β = 0.5%, p = 0.01) and native-T1 (β = 7 ms, p = 0.01) compared with those with normal HDL-C levels. Those with low HDL-C were not associated with IMF. Results remained unchanged after excluding individuals with a history of myocardial infarction. Neither increasing levels of HDL-C nor any HDL-C category was associated with the prevalence of myocardial scar. Increasing levels of HDL-C were associated with increased markers of IMF, with those with high levels of HDL-C being linked to subclinical fibrosis in a community-based setting.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The association of physical activity with the development and progression of coronary artery calcium (CAC) scores has not been studied. This study aimed to evaluate the prospective association ...between physical activity and CAC scores in apparently healthy adults.
Prospective cohort study of men and women free of overt cardiovascular disease who underwent comprehensive health screening examinations between 1 March 2011 and 31 December 2017. Baseline physical activity was measured using the International Physical Activity Questionnaire Short Form (IPAQ-SF) and categorised into three groups (inactive, moderately active and health-enhancing physically active (HEPA)). The primary outcome was the difference in the 5-year change in CAC scores by physical activity category at baseline.
We analysed 25 485 participants with at least two CAC score measurements. The proportions of participants who were inactive, moderately active and HEPA were 46.8%, 38.0% and 15.2%, respectively. The estimated adjusted average baseline CAC scores (95% confidence intervals) in participants who were inactive, moderately active and HEPA were 9.45 (8.76, 10.14), 10.20 (9.40, 11.00) and 12.04 (10.81, 13.26). Compared with participants who were inactive, the estimated adjusted 5-year average increases in CAC in moderately active and HEPA participants were 3.20 (0.72, 5.69) and 8.16 (4.80, 11.53). Higher physical activity was association with faster progression of CAC scores both in participants with CAC=0 at baseline and in those with prevalent CAC.
We found a positive, graded association between physical activity and the prevalence and the progression of CAC, regardless of baseline CAC scores.
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