Clinical Coronary Heart Disease Research Articles

Addition of Social Determinants of Health to Coronary Heart Disease Risk Prediction: The Multi-Ethnic Study of Atherosclerosis.

Social determinants of health (SDoH) are associated with cardiovascular risk factors and outcomes; however, they are absent from risk prediction models. We aimed to assess if the addition of SDoH improves the predictive ability of the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score. This was a community-based prospective population cohort study that enrolled 6286 men and women, ages 45-84 years, who were free of clinical coronary heart disease (CHD) at baseline. Data from 10-year follow-up were examined for CHD events, defined as myocardial infarction, fatal CHD, resuscitated cardiac arrest, and revascularization in cases of anginal symptoms. Participants included 53% women with average age of 62 years. When adjusting for traditional cardiovascular risk factors, SDoH, and coronary artery calcium, economic strain, specifically low family income, was associated with a greater risk of CHD events (hazard ratio [HR], 1.42 [95% CI, 1.17-1.71], P value<0.001). Area under the curve of risk prediction with SDoH was 0.822, compared with 0.816 without SDoH. The calibration slope was 0.860 with SDoH and 0.878 in the original model. Significant associations were found between economic/financial SDoH and CHD risk factors and outcomes. Incorporation of SDoH into the MESA Risk Score did not improve predictive ability of the model. Our findings do not support the incorporation of SDoH into current risk prediction algorithms.

Defining Demographic-specific Coronary Artery Calcium Percentiles in the Population Aged ≥75: The ARIC Study and MESA.

Current clinical guidelines recommend a coronary artery calcium (CAC) score of 100 Agatston Units or demographic-specific 75th percentile as high-risk thresholds for guiding atherosclerotic cardiovascular disease preventive therapy. Meanwhile, low CAC can help derisk individuals who may safely defer statin therapy. However, limited data from the early 2000s, including just 208 older Black individuals, inform CAC percentiles for adults aged 75 to 85 years, and none have been established in adults aged ≥85 years. This study aims to characterize the distribution of CAC and establish demographic-specific CAC percentiles in the population aged ≥75 years. We assessed 2886 participants aged ≥75 years without clinical coronary heart disease from the ARIC study (Atherosclerosis Risk in Communities) visit 7 (2018-2019; n=2217) and the MESA (Multi-Ethnic Study of Atherosclerosis) visit 5 (2010-2011; n=669). Prevalence of any CAC >0 and sex- and race-specific CAC percentiles across age were estimated nonparametrically with locally weighted regression models and pooled residual ranking. The median age was 80 (interquartile interval, 77-83) years, and 60% were female. The prevalence of zero CAC was lowest in White males (4%), followed by Black males (13%), White females (14%), and highest in Black females (18%). Regardless of sex and race, most participants had CAC>100 (62.5%). CAC scores increased with age, with CAC identified in ≈95% of participants aged ≥90 years across sex-race subgroups. The 75th percentile corresponded to higher CAC scores for Black older adults (n=741), especially females, than currently used thresholds. In community-dwelling adults aged ≥75 years free of clinical coronary heart disease, the prevalence of zero CAC was 11%, and CAC >100 as a threshold for high ASCVD risk would categorize most of this older population as high risk. Demographic-specific CAC percentiles from this study are a valuable tool for interpreting CAC in the population aged ≥75 years.

SR-B1-/-ApoE-R61h/h Mice Mimic Human Coronary Heart Disease.

Cardiovascular diseases are the leading cause of death in the modern world. Atherosclerosis underlies the majority of these pathologies and may result in sudden life-threatening events such as myocardial infarction or stroke. Current concepts consider a rupture (resp. erosion) of "unstable/vulnerable" atherosclerotic plaques as a primary cause leading to thrombus formation and subsequent occlusion of the artery lumen finally triggering an acute clinical event. We and others described SR-B1-/-ApoE-R61h/h mice mimicking clinical coronary heart disease in all major aspects: from coronary atherosclerosis through vulnerable plaque ruptures leading to thrombus formation/coronary artery occlusion, finally resulting in myocardial infarction/ischemia. SR-B1-/-ApoE-R61h/h mouse provides a valuable model to study vulnerable/occlusive plaques, to evaluate bioactive compounds as well as new anti-inflammatory and "anti-rupture" drugs, and to test new technologies in experimental cardiovascular medicine. This review summarizes and discuss our knowledge about SR-B1-/-ApoE-R61h/h mouse model based on recent publications and experimental observations from the lab.

Coronary Artery Calcium Score and Polygenic Risk Score for the Prediction of Coronary Heart Disease Events

Coronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts. To evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor-based model. Two observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands. Traditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score. Model discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed. The median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, -0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2<20). Subgroup analysis stratified by the median age demonstrated similar findings. Similar findings were observed for 10-year risk in RS and in longer-term follow-up in MESA (median, 16.0 years). In 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors.

Alcohol consumption and subclinical and clinical coronary heart disease: a Mendelian randomization analysis.

The potential effect of alcohol consumption on coronary heart disease (CHD) remains unclear. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in subclinical and clinical CHD. We conducted two Mendelian randomization studies: a cross-sectional study of coronary artery calcification (CAC) on computed tomography of 1029 healthy men (mean age, 63.8 years) and a case-control study of 421 men with CHD [acute coronary syndrome (ACS) or stable angina pectoris] who underwent coronary revascularization and 842 age-matched male controls. In the CAC study, medians (25%tiles, 75%tiles) of alcohol consumption by ALDH2-rs671 *2 homozygotes [n = 86 (8.4%)], *1*2 heterozygotes [n = 397 (38.5%)], and *1 homozygotes [n = 546 (53.1%)] were 0.0 (0.0, 0.0), 28.0 (0.0, 129.0), and 224.0 (84.0, 350.0) g/week, respectively. In age-adjusted Poisson regression with robust error variance, compared with *2 homozygotes, relative risks for prevalent CAC score >0, ≥100, and ≥300 in *1 homozygotes were 1.29 (95% confidence interval, 1.06-1.57), 1.76 (1.05-2.96), and 1.81 (0.80-4.09), respectively. In age-adjusted ordinal logistic regression for CAC distributions, we observed higher odds among *1 homozygotes [odds ratio, 2.19 (1.39-3.46)] and even among *1*2 heterozygotes [1.77 (1.11-2.82)] compared with *2 homozygotes. In the case-control study, conditional logistic regression revealed lower prevalence of *1 homozygotes among men with CHD [odds ratio, 0.54 (0.35-0.82)], especially ACS [0.46 (0.27-0.77)], than controls. Our findings indicate a positive association of alcohol consumption with CAC burden but an inverse association with clinical CHD, especially ACS.

Abstract MP61: 1-year Prognosis By Coronary Artery And Extra-coronary Calcification In The 75-and-older Population

Background: Coronary artery calcium (CAC) is one of the most potent predictors of cardiovascular disease (CVD). Also, thoracic extra-coronary calcification (ECC) (e.g., aortic valve calcification) has provided additional prognostic information beyond CAC. However, data on CAC and ECC as predictors of CVD outcomes are limited in individuals aged ≥75 years and rarely report near-term prognosis despite its importance in the 75-and-older population given life expectancy. Methods: In 1,672 ARIC participants (age 75-94 years) without history of clinical coronary heart disease (CHD) at visit 7 (2018-2019), we assessed the associations of CAC and ECC with CVD (including CHD, stroke, and heart failure) over a median follow-up of 1.1 (IQI 0.7-1.5) years (46 CVD total cases), using adjusted Cox models. CAC and ECC were modeled categorically (Agatston scores 0-99 [reference], 100-299, and 300+) and continuously (log[Agatston score+1]). Results: Higher scores of CAC and calcium in the aortic valve (only when modeled continuously) and ascending aorta were significantly associated with elevated risk of CVD (e.g., adjusted hazard ratio [HR]: 2.79 [95% CI 1.21, 6.44] for CAC 300+ and 5.90 [2.42, 14.39] for ascending aorta calcium 300+ vs. 0-99.) ( Table ). We confirmed consistent results after excluding participants with prevalent stroke, and the association of aortic valve calcium 300+ with CVD became statistically significant (HR 2.31 [95% CI 1.02, 5.24]. When each CVD outcome was analyzed separately, significant associations with CHD and heart failure were shown in CAC (only when modeled continuously) and ascending aorta calcium (e.g., 4.98 [95% CI 1.10, 22.58] for CHD and 6.88 [2.14, 22.04] in ascending aorta calcium 300+). Conclusions: Coronary artery, ascending aorta, and aortic valve calcifications were positively associated with 1-year risk of CVD in 75+ year old. Our results support the prognostic value of CAC and ECC even in very old adults and suggest distinct prognostic implications of different vascular beds.

Carotid plaque is strongly associated with coronary artery calcium and predicts incident coronary heart disease in a population-based cohort

Background and aimsCoronary artery calcium (CAC) and carotid plaque are markers of atherosclerosis and predict future coronary heart disease (CHD) events. The aim of this study was to investigate associations between CAC and carotid plaque in asymptomatic individuals, also in relation to predicted CHD-risk and incident events. A secondary aim was to compare predictive value between CAC, carotid plaque, and total carotid plaque area (TPA) as predictors for future CHD-events. MethodsThe REFINE-Reykjavik study is prospective and population-based with CAC-scoring and carotid plaque ultrasound assessment, both presence and area. A total of 948 individuals without clinical CHD were included in the study. CAC scores were categorized into 0,1–100,101-300 and > 300, and carotid plaque into none, minimal and significant. Three models were applied adjusted for age, sex, and each of the Framingham risk score (FRS), local CHD risk score and established CHD risk factors. ResultsCombined carotid plaque- and CAC-presence was highly prevalent, 69.5% for males and 41.7% for females (54.5% overall). TPA outperformed base models in CHD prediction, resulting in statistically significant area under the receiver operator characteristic curve (AUC) increase ranging from 0.02 to 0.05. Most CHD-events in females occurred in individuals classified as low-risk with respect to traditional risk factors but with a gradient in observed risk across carotid plaque categories. ConclusionsCarotid plaque was strongly associated with the presence and extent of CAC in asymptomatic individuals in a population-based cohort. Carotid plaque predicts incident CHD events over risk scores and may be useful for refined risk prediction in females.

Abstract 13428: Mid-Life and Late-Life Exposure to Traditional Cardiovascular Risk Factors and Zero Coronary Artery Calcium: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Our understanding of traditional atherosclerotic risk factors is largely based on their contributions to adverse atherosclerotic events. However, the relative contributions of mid-life and late-life risk factor exposures to persistent zero coronary artery calcium (CAC=0) in older adulthood, a representative healthy vascular aging phenotype, have not been fully examined. Hypothesis: Both mid-life and late-life risk factors are associated with CAC=0, with stronger results for the former. Methods: Using data from 2,035 community-dwelling participants free of coronary heart disease in the ARIC study, we evaluated traditional modifiable risk factors (i.e., lipids, systolic blood pressure, obesity, smoking, and diabetes) at mid-life (median age 49, visit 1 from 1987-1989) and late-life (median age 73, visit 5 from 2011-2013) and their associations with CAC=0 at visit 7 (median age 80, from 2018-2019), using multivariable logistic regression models adjusted for within-visit factors. Results: There were 204 participants (10.0%) with CAC=0. Compared with participants with any CAC, those with CAC=0 had more favorable values for most traditional risk factors (lower cholesterol, BMI, and systolic blood pressure, higher HDL-C, and not smoking) in both mid-life and late-life, with the exception of fasting glucose ( Table ). The results were similar when we modeled diabetes instead of fasting glucose. Lower total cholesterol in mid-life, but not late-life, was associated with CAC=0. Conclusions: Having favorable modifiable risk factors both at mid-life and late-life were independently associated with CAC=0 in older adults free of clinical coronary heart disease. These results highlight the importance of maintaining a healthy risk factor profile from mid-life, with implications on public health promotion and strategy.

Associations of exposure to residential green space and neighborhood walkability with coronary atherosclerosis in Chinese adults

Residential green space and neighborhood walkability are important foundations of a healthy and sustainable city. Yet, their associations with atherosclerosis, the disease underlying clinical coronary heart disease (CHD), is unknown, especially in susceptible populations. We aim to explore the associations of exposure to residential green space and neighborhood walkability with coronary atherosclerosis. In this study of 2021 adults with suspected CHD, we evaluated the associations of exposure to green space (using Normalized Difference Vegetation Index [NDVI] and enhanced vegetation index [EVI] surrounding each participant's home) and neighborhood walkability (using walkability index and number of parks near home) with atherosclerosis (using coronary artery calcium score, CAC) using linear regression model adjusted for individual-level characteristics. Mediation analysis was further applied to explore potential mechanisms through the pathways of physical activity, air pollution, and psychological stress. In the primary model, an interquartile increase in annual mean NDVI and EVI within the 1-km area was associated with −15.8% (95%CI: 28.7%, −0.7%), and −18.6% (95%Cl: 31.3%, −3.6%) lower CAC score, respectively. However, an interquartile increase in the walkability index near home was associated with a 7.4% (95% CI: 0.1%, 15.2%) higher CAC score. The combined exposure to a green space area in a 1-km area and the walkability index were inversely associated with atherosclerosis, albeit with a smaller magnitude than a single-exposure model. The findings from a mediation analysis suggested that increased physical exercise and ameliorated particulate matter <2.5 μm (PM2.5) may partially contribute to the relationship between green space and atherosclerosis, and for walkability index, partially explained by increased PM2.5 exposure. Our study suggested a beneficial association between green space and atherosclerosis, but an adverse association between neighborhood walkability and atherosclerosis. Therefore, urban development that aims to improve neighborhood walkability should jointly account for enhancing green space properties from a public health perspective.

Characteristic analysis of clinical coronary heart disease and coronary artery disease concerning young and middle-aged male patients.

BACKGROUNDCoronary heart disease (CHD) is a type of coronary atherosclerotic heart disease. In recent years, the incidence of CHD has been increasing annually, with an increasing number of young patients. Severe CHD may cause severe myocardial ischemia or myocardial necrosis, which in turn may cause myocardial infarction and related complications that seriously affect the life and health of the patient.AIMTo examine the coronary arteries and clinical features of young and middle-aged male patients with CHD.METHODSFrom February 2019 to January 2020, 110 male CHD patients admitted to our hospital were selected as research subjects and were divided into two groups by age: middle-aged group (n = 55) and young group (n = 55). The coronary arteries and clinical features of the patients were compared.RESULTSThere were no significant differences in dyslipidemia, stroke history, high-density lipoprotein cholesterol, or triacylglycerol (P > 0.05) between the two groups. In the young group, age, diabetes, hypertension, smoking history, body mass index, family history of CHD, drinking history, fibrinogen, low-density lipoprotein cholesterol, total cholesterol, and single-vessel disease were higher than those in the middle-aged group. Correspondingly, serum uric acid, hyperuricemia, myocardial infarction, Gensini score > 50, collateral circulation, multivessel disease, double vessel disease, involvement of the right coronary artery, and involvement of the left main coronary artery were lower in the young group than in the middle-aged group. The middle-aged group mainly suffered from a high Gensini score, implicating multiple arteries, whereas the young group was mainly affected by single-vessel disease. The between-group difference was significant (P < 0.05).CONCLUSIONIn CHD attacks, multiple coronary arteries are implicated in middle-aged male patients and single-vessel disease in young male patients.

Abstract P213: Characterizing The Distribution Of Coronary Artery Calcification In The 75-and-older Population: The Atherosclerosis Risk In Communities Study

Introduction: The coronary artery calcium (CAC) score is a strong predictor of atherosclerotic cardiovascular disease (ASCVD) events. Current clinical practice guidelines recommend using a CAC score of 100 or age-, sex-, and race-specific 75 th percentile as thresholds of high risk for guiding preventive therapy for ASCVD. On the low end of the spectrum, zero CAC attracts attention as a potent negative predictor of ASCVD and may be used to “de-risk” individuals who may safely defer aggressive preventive therapy. However, due to sparse data on CAC in the age 75+ population, the value of these CAC thresholds in older adults is uncertain. Objective: To understand the distribution of CAC (75 th percentile, CAC 100, and zero CAC) in adults aged 75+. Methods: We assessed 2,303 ARIC Visit 7 (2018-2019) participants age 75+ years without clinical coronary heart disease (CHD) who underwent CAC scanning (median age 80 years, 39% males). Demographic-specific percentiles of the CAC distribution across age were estimated nonparametrically with pooled residual ranking and locally weighted regressions. Results: Male-white and male-black participants had lower prevalence of zero CAC than female-white and female-black participants (4% and 10% versus 13% and 16%, respectively). CAC scores tended to increase with age across race and sex strata but appeared to peak at an old age threshold (between age~85-95) ( Figure ). Regardless of age, sex, and race, a majority of individuals in this age range had CAC &gt;100 ( Figure , green 50 th percentile line exceeds red dashed CAC 100 line at most ages). Conclusions: In the largest US cohort of community-dwelling adults aged 75+ free of clinical CHD with CAC data, the prevalence of zero CAC was approximately 4-16%. We also confirmed a general age-dependent increase in CAC. Using CAC &gt;100 as a threshold for high ASCVD risk would categorize the majority of older adults age 75+ as high risk. Alternatively, our demographic-specific CAC percentiles may be a valuable tool for interpreting CAC in the age 75+ population.

Physical Activity, Inflammation, Coronary Artery Calcification, and Incident Coronary Heart Disease in African Americans: Insights From the Jackson Heart Study

ObjectiveTo examine associations between physical activity (PA), inflammation, coronary artery calcification (CAC), and incident coronary heart disease (CHD) in African Americans. MethodsAmong Jackson Heart Study participants without prevalent CHD at baseline (n=4295), we examined the relationships between PA and high-sensitivity C-reactive protein, the presence of CAC (Agatston score ≥100), and incident CHD. Based on the American Heart Association’s Life’s Simple 7 metrics, participants were classified as having poor, intermediate, or ideal PA. ResultsAfter adjustment for possible confounding factors, ideal PA was associated with lower high-sensitivity C-reactive protein levels (β, −0.15; 95% CI, −0.15 to −0.002) and a lower prevalence of CAC (odds ratio, 0.70; 95% CI, 0.51-0.96) compared with poor PA. During a median of 12.8 years of follow-up, there were 164 incident CHD events (3.3/1000 person-years). Ideal PA was associated with a lower rate of incident CHD compared with poor PA (hazard ratio, 0.55; 95% CI, 0.31-0.98). ConclusionIn a large community-based African American cohort, ideal PA was associated with lower inflammation levels, a lower prevalence of CAC, and a lower rate of incident CHD. These findings suggest that promotion of ideal PA may be an important way to reduce the risk of subclinical and future clinical CHD in African Americans.

Associations between family history and coronary artery calcium and coronary heart disease in British Europeans and South Asians

BackgroundThe role of family history in determining excess risk of coronary heart disease (CHD) in South Asians compared with Europeans is unclear. We hypothesized that family history would be more strongly associated with CHD in South Asians. MethodsWe performed cross-sectional analyses of 20-year follow-up data from SABRE (Southall And Brent Revisited) population-based study. Initial recruitment (1988–1991) was by random selection from general practitioners' lists in north-west London. 974 Europeans and 734 South Asians completed follow-up questionnaire (2008–2011) and had complete CHD and family history data. 831 participants without cardiovascular disease had complete coronary artery calcium (CAC) data. ResultsSouth Asians with family history of CHD were more likely to have diagnosed CHD (odds ratio 1.71 [95% CI 1.21, 2.42]; p = 0.002) and more previous CHD events (regression coefficient 0.44 [0.16, 0.72]; p = 0.002) than those without family history, independent of biological and sociodemographic risk factors. Family history associations with diagnosed CHD/number of events were weaker in Europeans (odds ratio 1.11 [0.78, 1.57]; p = 0.562/regression coefficient 0.02 [−0.25, 0.30]; p = 0.878), largely explained by biological risk factors. South Asians with family history had modestly increased CAC burden compared with Europeans. ConclusionsThere were markedly stronger associations between family history and clinical CHD in South Asians, and a similar trend for subclinical CHD. Early preventive and therapeutic interventions are particularly important in South Asians with a family history of CHD.

Low T3 syndrome is a predominant thyroid dysfunction among coronary heart disease patients: an Egyptian angiographic study

Background Cardiovascular diseases are the most common cause of mortality, primarily affecting older adults. Although the established risk factors explain most cardiac risks, alternative biochemical markers may have an assisting diagnostic role in identifying those at risk for a clinical cardiovascular event, among the abnormal thyroid gland profiles. Aim We aimed to investigate the cardiovascular risk of thyroid profile abnormalities among patients with clinical coronary heart disease (CHD) confirmed by coronary angiography (CA). Patients and methods An observational, prospective case–control study. Ninety cases participated in the study. They were divided into two groups: Group I (n=60) CHD patients were diagnosed by percutaneous (CA) and group II (30 participants) with negative diagnostic workup for CHD who were enrolled as the control group or (non-CHD group). Thyroid hormones profiles were withdrawn from both groups. Results Group I (CHD patients proved by CA) had statistically significant higher age (55.18±12.303 vs. 48.73±13.014 years, P=0.024), blood glucose (207.55±74.186 mg%; P=0.002), blood urea (37.65±12.658 vs. 28.97±9.152 mg%, P=0.001), and cholesterol (246.67+99.348 vs. 199.67±47.593 mg%, P=0.003). T3 levels are significantly lower in group I (2.094±0.971 vs. 2.73+0.7221 pg/ml, P=0.002). Conclusion Our results concluded that low T3 syndrome is the predominant thyroid dysfunction in CHD patients who underwent a CA.

Association Between Plasma Neutrophil Gelatinase-Associated Lipocalin and Cardiac Disease Hospitalizations and Deaths in Older Women.

BackgroundNeutrophil gelatinase‐associated lipocalin (NGAL) or lipocalin 2 may promote atherosclerosis and plaque instability leading to increased risk of cardiac events. We investigated the relationships between plasma NGAL, cardiovascular disease biomarkers, and long‐term cardiac events.Methods and ResultsThe study population consisted of 1131 ambulant older white women (mean age 75 years) without clinical coronary heart disease (CHD) and measures of plasma NGAL in the Perth Longitudinal Study of Ageing Women with 14.5‐year CHD and heart failure hospitalizations or death (events) captured using linked records. Over 14.5 years, 256 women had CHD events, while 118 had heart failure events. Per SD increase in log‐transformed NGAL there was a 35% to 37% increase in relative hazards for CHD and heart failure events in unadjusted analyses, which remained significant after adjustment for conventional risk factors for CHD events (hazard ratio 1.29, 95% CI 1.13–1.48, P<0.001) but not heart failure (P>0.05). Women in the highest 2 quartiles of NGAL had higher relative hazards for CHD events compared with women in the lowest quartile hazard ratio 1.61, 95% CI 1.08–2.39, P=0.019 and hazard ratio 1.97, 95% CI 1.33–3.93, P=0.001, respectively. These associations were independent of high‐sensitivity cardiac troponin I, homocysteine, and estimated renal function. NGAL correctly reclassified 1 in 4 women who sustained a CHD event up in risk and 1 in 10 women without CHD events down in risk.Conclusions NGAL was associated with increased risk of long‐term CHD events, independent of conventional risk factors and biomarkers. These findings provide mechanistic insight into the role of NGAL with cardiac events.

IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)

BackgroundCertain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.ObjectivesWe tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics.MethodsNORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386 days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively.FindingsFrom 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p = 0.012; p = 0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p = 0.027) and percentage of plaque occupied by necrotic core (p = 0.011), as well as lipid core burden index (p = 0.024) in the worst 4 mm segment.InterpretationOur study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.

The research progress of clinical prophylaxis with aspirin

Aspirin is a non-steroidal anti-inflammatory drug, has good antipyretic and analgesic effects, but also inhibits platelet aggregation and antithrombotic effects, commonly used in clinical coronary heart disease and cerebrovascular disease in first grade, two grade prevention.The need to pay attention to the medication time, interaction, the risk of bleeding, medication use in special populations in the process, to ensure the reasonable clinical medication of aspirin.This review summarizes the research progress of aspirin prophylaxis. Key words: Aspirin; Application; Safety

The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease.

Numerous clinical trials suggest that we have reached a limit in our ability to decrease the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) utilizing the traditional diagnostic evaluation, prevention and treatment strategies for the top five cardiovascular risk factors of hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. About 80% of heart disease (heart attacks, angina, coronary heart disease and congestive heart failure) can be prevented by optimal nutrition, optimal exercise, optimal weight and body composition, mild alcohol intake and avoiding smoking. Statistics show that approximately 50% of patients continue to have CHD or myocardial infarction (MI) despite presently defined 'normal' levels of the five risk factors listed above. This is often referred to as the 'CHD gap'. Novel and more accurate definitions and evaluations of these top five risk factors are required, such as 24 h ambulatory blood pressure (ABM) results, advanced lipid profiles, redefined fasting and 2 h dysglycemia parameters, a focus on visceral obesity and body composition and the effects of adipokines on cardiovascular risk. There are numerous traumatic insults from the environment that damage the cardiovascular system but there are only three finite vascular endothelial responses, which are inflammation, oxidative stress and immune vascular dysfunction. In addition, the concept of translational cardiovascular medicine is mandatory in order to correlate the myriad of CHD risk factors to the presence or absence of functional or structural damage to the vascular system, preclinical and clinical CHD. This can be accomplished by utilizing advanced and updated CV risk scoring systems, new and redefined CV risk factors and biomarkers, micronutrient testing, cardiovascular genetics, nutrigenomics, metabolomics, genetic expression testing and noninvasive cardiovascular testing.

Clinical trials in menopause.

Clinical trials in menopause have undergone much scrutiny over the years. This has led to significant shifts in the treatment of symptomatic menopause and a substantial impact on women. We aim to delineate the key studies contributing to this controversy and highlight new directions specifically related to menopausal hormone therapy (HT) and vascular disease risk. We performed a search of sentinel studies delineating the risks and benefits of HT in otherwise healthy postmenopausal women. Using PubMed we input the following search terms: hormone replacement therapy, cardiovascular disease, coronary artery disease, coronary atherosclerosis, myocardial infarction, angina, coronary heart calcification, carotid intimal thickness, lipids, and/or lipoproteins. We included studies of menopausal women (surgical or natural) using combined estrogen/progestogen therapy or estrogen-only therapy that looked at cardiovascular disease risk factors or outcomes. Studies were evaluated for inclusion by the authors; however, this is not intended to be a systematic or an exhaustive analysis. In women close to the time of menopause, there is a decreased risk of subclinical and clinical coronary heart disease with menopausal HT. Additionally, HT confers a significant benefit to vasomotor symptoms of menopause, bone health, and colorectal cancer. There is an increased risk of venous thromboembolism with oral formulations that appears mitigated with transdermal estradiol. Mixed data regarding breast cancer risk are available, with some studies suggesting an increased risk of invasive breast cancer with estrogen/progestogen therapy and a null effect with estrogen-only therapy. Other more long-term epidemiologic studies identify a decreased risk. The available literature suggests that HT is a viable option for the primary prevention of cardiovascular disease in postmenopausal women. Newer trials will likely verify this assessment. If this is enough to change clinical practice, however, remains to be seen given the general fear of HT by many with prescriptive authority, and also the women in our care.

Physical Activity and Mortality in Patients With Stable Coronary Heart Disease

BackgroundRecommendations for physical activity in patients with stable coronary heart disease (CHD) are based on modest evidence. ObjectivesThe authors analyzed the association between self-reported exercise and mortality in patients with stable CHD. MethodsA total of 15,486 patients from 39 countries with stable CHD who participated in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) study completed questions at baseline on hours spent each week taking mild, moderate, and vigorous exercise. Associations between the volume of habitual exercise in metabolic equivalents of task hours/week and adverse outcomes during a median follow-up of 3.7 years were evaluated. ResultsA graded decrease in mortality occurred with increased habitual exercise that was steeper at lower compared with higher exercise levels. Doubling exercise volume was associated with lower all-cause mortality (unadjusted hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.79 to 0.85; adjusting for covariates, HR: 0.90; 95% CI: 0.87 to 0.93). These associations were similar for cardiovascular mortality (unadjusted HR: 0.83; 95% CI: 0.80 to 0.87; adjusted HR: 0.92; 95% CI: 0.88 to 0.96), but myocardial infarction and stroke were not associated with exercise volume after adjusting for covariates. The association between decrease in mortality and greater physical activity was stronger in the subgroup of patients at higher risk estimated by the ABC-CHD (Age, Biomarkers, Clinical–Coronary Heart Disease) risk score (p for interaction = 0.0007). ConclusionsIn patients with stable CHD, more physical activity was associated with lower mortality. The largest benefits occurred between sedentary patient groups and between those with the highest mortality risk.