Glucagon-Like Peptide 1 Receptor Agonists: A Medication for Obesity Management.

PURPOSE OF REVIEW: The burden of obesity worldwide is high and projected to rise. Obesity increases the risk of several cardiovascular diseases and cardiometabolic risk factors; hence, utilizing effective long-term therapies for obesity is of utmost importance. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as effective therapies that achieve substantial weight loss and improve cardiometabolic risk. The purpose of this review is to discuss the role of GLP-1RAs in obesity management. RECENT FINDINGS: Two subcutaneous GLP-1RAs, liraglutide and semaglutide, have been evaluated in several clinical trials for weight loss. Liraglutide achieves a mean weight loss of 4-7 kg, and more than 50% of treated individuals achieve 5% or more weight loss. Semaglutide has a greater impact on weight loss, with a mean weight loss of 9-16 kg, and more than 50% of treated individuals achieve 10-15% or more weight loss. These results led to regulatory approval of these agents for weight loss in individuals with obesity, regardless of diabetes status. In addition to weight loss, the benefits of GLP-1RAs extend to other risk factors, such as glycemic control and blood pressure. Gastrointestinal symptoms are the most frequently encountered adverse events with incidences between 5 and 30%. Finally, the cost remains one of the most critical challenges that limit GLP-1RAs use. GLP-1RAs have robust weight loss benefits and are expected to have a critical role in the management of obesity in the coming years. Upcoming studies will evaluate the durability of weight loss achieved with GLP-1RAs and the impact on cardiovascular outcomes.

The relationship of erectile dysfunction and subclinical cardiovascular disease: A systematic review and meta-analysis.

Erectile dysfunction (ED) is associated with cardiovascular disease (CVD) and CVD mortality. However, the relationship between ED and subclinical CVD is less clear. We synthesized the available data on the association of ED and measures of subclinical CVD. We searched multiple databases for published literature on studies examining the association of ED and measures of subclinical CVD across four domains: endothelial dysfunction measured by flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), coronary artery calcification (CAC), and other measures of vascular function such as the ankle-brachial index, toe-brachial index, and pulse wave velocity. We conducted random effects meta-analysis and meta-regression on studies that examined an ED relationship with FMD (15 studies; 2025 participants) and cIMT (12 studies; 1264 participants). ED was associated with a 2.64 percentage-point reduction in FMD compared to those without ED (95% CI: -3.12, -2.15). Persons with ED also had a 0.09-mm (95% CI: 0.06, 0.12) higher cIMT than those without ED. In subgroup meta-analyses, the mean age of the study population, study quality, ED assessment questionnaire (IIEF-5 or IIEF-15), or the publication date did not significantly affect the relationship between ED and cIMT or between ED and FMD. The results for the association of ED and CAC were inconclusive. In conclusion, this study confirms an association between ED and subclinical CVD and may shed additional light on the shared mechanisms between ED and CVD, underscoring the importance of aggressive CVD risk assessment and management in persons with ED.

Association between self-rated health and ideal cardiovascular health: The Baptist Health South Florida Employee Study.

Background: There is increasing evidence of the role psychosocial factors play as determinants of cardiovascular health (CVH). We examined the association between self-rated health (SRH) and ideal CVH among employees of a large healthcare organization. Methods: Data were collected in 2014 from employees of Baptist Health South Florida during an annual voluntary health risk assessment and wellness fair. SRH was measured using a self-administered questionnaire where responses ranged from poor, fair, good, very good to excellent. A CVH score (the proxy for CVH) that ranged from 0 to 14 was calculated, where 0-8 indicate an inadequate score, 9-10, average and 11-14, optimal. A multinomial logistic regression was used to examine the association between SRH and CVH. Results: Of the 9056 participants, 75% were female and mean age (SD) was 43 ± 12 years. The odds of having a higher CVH score increased as SRH improved. With participants who reported their health status as poor-fair serving as reference, adjusted odds ratios for having an optimal CVH score by the categories of SRH were: excellent, 21.04 (15.08-29.36); very good 10.04 (7.25-13.9); and good 3.63 (2.61-5.05). Conclusion: Favorable SRH was consistently associated with better CVH.

Volumetric Single-Beat Coronary Computed Tomography Angiography: Relationship of Image Quality, Heart Rate, and Body Mass Index. Initial Patient Experience With a New Computed Tomography Scanner.

BACKGROUND: Cardiac computed tomography (CT) image quality (IQ) is very important for accurate diagnosis. We propose to evaluate IQ expressed as Likert scale, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) from coronary CT angiography images acquired with a new volumetric single-beat CT scanner on consecutive patients and assess the IQ dependence on heart rate (HR) and body mass index (BMI). METHODS: We retrospectively analyzed the data of the first 439 consecutive patients (mean age, 55.13 [SD, 12.1] years; 51.47% male), who underwent noninvasive coronary CT angiography in a new single-beat volumetric CT scanner (Revolution CT) to evaluate chest pain at West Kendall Baptist Hospital. Based on patient BMI (mean, 29.43 [SD, 5.81] kg/m), the kVp (kilovolt potential) value and tube current were adjusted within a range of 80 to 140 kVp and 122 to 720 mA, respectively. Each scan was performed in a single-beat acquisition within 1 cardiac cycle, regardless of the HR. Motion correction software (SnapShot Freeze) was used for correcting motion artifacts in patients with higher HRs. Autogating was used to automatically acquire systolic and diastolic phases for higher HRs with electrocardiographic milliampere dose modulation. Image quality was assessed qualitatively by Likert scale and quantitatively by SNR and CNR for the 4 major vessels right coronary, left main, left anterior descending, and left circumflex arteries on axial and multiplanar reformatted images. Values for Likert scale were as follows: 1, nondiagnostic; 2, poor; 3, good; 4, very good; and 5, excellent. Signal-to-noise ratio and CNR were calculated from the average 2 CT attenuation values within regions of interest placed in the proximal left main and proximal right coronary artery. For contrast comparison, a region of interest was selected from left ventricular wall at midcavity level using a dedicated workstation. We divided patients in 2 groups related to the HR: less than or equal to 70 beats/min (bpm) and greater than 70 bpm and also analyzed them in 2 BMI groupings: BMI less than or equal to 30 kg/m and BMI greater than 30 kg/m. RESULTS: Mean SNR was 8.7 (SD, 3.1) (n = 349) for group with HR 70 bpm or less and 7.7 (SD, 2.4) (n = 78) for group with HR greater than 70 bpm (P = 0.008). Mean CNR was 6.9 (SD, 2.7) (n = 349) for group with HR 70 bpm or less and 5.9 (SD, 2.2) (n = 78) for group with HR 70 bpm or greater (P = 0.002). Mean SNR was 8.8 (SD, 3.2) (n = 249) for group with BMI 30 kg/m or less and 8.1 (SD, 2.6) (n = 176) for group with BMI greater than 30 kg/m (P = 0.008). Mean CNR was 7.0 (SD, 2.8) (n = 249) for group with BMI 30 kg/m or less and 6.4 (SD, 2.4) (n = 176) for group with BMI greater than 30 kg/m (P = 0.002). The results for mean Likert scale values were statistically different, reflecting difference in IQ between people with HR 70 bpm or less and greater than 70 bpm, BMI 30 kg/m or less, and BMI greater than 30 kg/m.

Dyslipidemia, coronary artery calcium, and incident atherosclerotic cardiovascular disease: implications for statin therapy from the multi-ethnic study of atherosclerosis.

BACKGROUND: Worldwide clinical practice guidelines for dyslipidemia emphasize allocating statin therapy to those at the highest absolute atherosclerotic cardiovascular disease (CVD) risk. METHODS AND RESULTS: We examined 5534 Multi-Ethnic Study of Atherosclerosis (MESA) participants who were not on baseline medications for dyslipidemia. Participants were classified by baseline coronary artery calcium (CAC) score (>0, ≥ 100) and the common clinical scheme of counting lipid abnormalities (LA), including low-density lipoprotein cholesterol ≥ 3.36 mmol/L (130 mg/dL), high-density lipoprotein cholesterol <1.03 mmol/L (40 mg/dL) for men or <1.29 mmol/L (50 mg/dL) for women, and triglycerides ≥ 1.69 mmol/L (150 mg/dL). Our main outcome measure was incident CVD (myocardial infarction, angina resulting in revascularization, resuscitated cardiac arrest, stroke, cardiovascular death). Over a median follow-up of 7.6 years, more than half of events (55%) occurred in the 21% of participants with CAC ≥ 100. Conversely, 65% of events occurred in participants with 0 or 1 LA. In those with CAC ≥ 100, CVD rates ranged from 22.7 to 29.5 per 1000 person-years across LA categories. In contrast, with CAC=0, CVD rates ranged from 2.7 to 5.9 per 1000 person-years across LA categories. Individuals with 0 LA and CAC ≥ 100 had a higher event rate compared with individuals with 3 LA but CAC=0 (22.7 versus 5.9 per 1000 person-years). Similar results were obtained when we classified LA using data set quartiles of total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or low-density lipoprotein particle concentration and guideline categories of low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol. CONCLUSIONS: CAC may have the potential to help match statin therapy to absolute CVD risk. Across the spectrum of dyslipidemia, event rates similar to secondary prevention populations were observed for patients with CAC ≥ 100.

Obesity Modifies the Effect of Fitness on Heart Rate Indices during Exercise Stress Testing in Asymptomatic Individuals.

OBJECTIVE: To assess the impact of aerobic fitness on exercise heart rate (HR) indices in an asymptomatic cohort across different body mass index (BMI) categories. METHODS: We performed a cross-sectional analysis of 506 working-class Brazilian subjects, free of known clinical cardiovascular disease(e.g. ischemic heart disease and stroke) who underwent an exercise stress test. RESULTS: There was a significant trend towards decreased HR at peak exercise, HR recovery and chronotropic index (CI) measures as BMI increased, but resting HR increased significantly across BMI categories. In multivariate analysis, the change in CI per unit change in metabolic equivalents of task was greater among the obese subjects than the normal-weight (2.7 vs. ­0.07; p interaction = 0.029)and overweight (2.7 vs. 0.7; p interaction = 0.044) subjects. A similar pattern was seen with peak HR and HR recovery, although the formal tests of interaction did not achieve statistical significance. CONCLUSION: Our findings strongly suggest that fitness is associated with a favorable HR profile and is modified by BMI. Intervention programs should place emphasis on fitness and not only on weight loss.

Low HDL cholesterol but not high LDL cholesterol is independently associated with subclinical coronary atherosclerosis in healthy octogenarians.

AIM OF THE STUDY: Although low-density lipoprotein cholesterol (LDL-C) has been consistently demonstrated a predictor of atherosclerotic disease in a large spectrum of clinical settings, among individuals aged of 80 years or older this concept is uncertain. This study was evaluated in a carefully selected population if the association between LDL-C and coronary atherosclerotic burden remains significant in the very elderly. METHODS: Individuals aged of 80 years or older (n = 208) who spontaneously sought primary prevention care and have never manifested cardiovascular disease, malnutrition, neoplastic or consumptive disease were enrolled for a cross-sectional analysis. Medical evaluation, anthropometric measurements, blood tests and cardiac computed tomography were obtained. RESULTS: In analyses adjusted for age, gender, diabetes, systolic and diastolic blood pressure, smoking and statin therapy, no association was found between coronary calcium score (CCS) and LDL-C [1.79 (0.75-4.29)]. There was no association between triglycerides and CCS. The association between high-density lipoprotein cholesterol (HDL-C) and CCS was significant and robust in unadjusted [0.32 (0.15-0.67)] as well as in the fully adjusted analysis [0.34 (0.15-0.75)]. CONCLUSION: The present study confirms in a healthy cohort of individuals aged of 80 years or more that while the association between LDL-C and coronary atherosclerosis weakens with aging, the opposite occurs with the levels of HDL-C.

Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis.

AIMS: We sought to evaluate the impact of coronary artery calcium (CAC) in individuals at the extremes of risk factor (RF) burden. METHODS AND RESULTS: 6698 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for coronary heart disease (CHD) events over mean 7.1 ± 1 years. Annualized CHD event rates were compared among each RF category (0, 1, 2, or ≥3) after stratification by CAC score (0, 1-100, 101-300, and >300). The following traditional modifiable RFs were considered: cigarette smoking, LDL cholesterol ≥3.4 mmol/L, low HDL cholesterol, hypertension, and diabetes. There were 1067 subjects (16%) with 0 RFs, whereas 1205 (18%) had ≥3 RFs. Among individuals with 0 RFs, 68% had CAC 0, whereas 12 and 5% had CAC >100 and >300, respectively. Among individuals with ≥3 RFs, 35% had CAC 0, whereas 34 and 19% had CAC >100 and >300, respectively. Overall, 339 (5.1%) CHD events occurred. Individuals with 0 RFs and CAC >300 had an event rate 3.5 times higher than individuals with ≥3 RFs and CAC 0 (10.9/1000 vs. 3.1/1000 person-years). Similar results were seen across categories of Framingham risk score. CONCLUSION: Among individuals at the extremes of RF burden, the distribution of CAC is heterogeneous. The presence of a high CAC burden, even among individuals without RFs, is associated with an elevated event rate, whereas the absence of CAC, even among those with many RF, is associated with a low event rate. Coronary artery calcium has the potential to further risk stratify asymptomatic individuals at the extremes of RF burden.

Beyond BMI: The "Metabolically healthy obese" phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality -- a systematic review.

BACKGROUND: A subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population. METHODS: Pubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or subclinical CVD. RESULTS: A total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define "metabolically healthy", while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study (14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts. CONCLUSIONS: MHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.

C-reactive protein is independently associated with coronary atherosclerosis burden among octogenarians.

AIM OF THE STUDY: In contrast to the general population, individuals with primarily persistent elevation of inflammatory activity display a significant association between inflammatory biomarkers and atherosclerotic burden. In older individuals, immunosenescence upregulates the innate response and, by this way, may hypothetically favor the presence of this association. The aim of this study was to evaluate this hypothesis in healthy octogenarians. METHODS: Participants (n = 208) aged 80 years or older, asymptomatic and without medical and laboratory evidence of chronic diseases or use of anti-inflammatory treatments were included in the study. Lipid profile and plasma C-reactive protein (CRP) were measured at baseline and cardiac computed tomography was performed within 1-week interval for measuring coronary calcium score (CCS). RESULTS: The median plasma CRP was 1.9 mg/L (1.0­3.4) and 33 % of the participants had elevated CRP defined as C3 mg/L. Among those with high CRP, there was an increased frequency of high CCS (C100) as compared with their counterparts (71 vs 50 %, p = 0.001). The association between CRP and CCS persisted even after adjustment for age, sex, cardiovascular risk factors and statin therapy. The area under the receiver-operating curve for CRP was 0.606 using CCS C100 as a binary outcome. The sensitivities for CCS C100 were 40 and 74 % for the cutoff points of CRP C3 or 1 mg/L, respectively. CONCLUSION: The present study was able to confirm that in very elderly individuals, systemic inflammatory activity is independently associated with coronary atherosclerosis burden.

Low-risk lifestyle, coronary calcium, cardiovascular events, and mortality: results from MESA.

Unhealthy lifestyle habits are a major contributor to coronary artery disease. The purpose of the present study was to investigate the associations of smoking, weight maintenance, physical activity, and diet with coronary calcium, cardiovascular events, and mortality. US participants who were 44-84 years of age (n = 6,229) were followed in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2010. A lifestyle score ranging from 0 to 4 was created using diet, exercise, body mass index, and smoking status. Coronary calcium was measured at baseline and a mean of 3.1 (standard deviation, 1.3) years later to assess calcium progression. Participants who experienced coronary events or died were followed for a median of 7.6 (standard deviation, 1.5) years. Participants with lifestyle scores of 1, 2, 3, and 4 were found to have mean adjusted annual calcium progressions that were 3.5 (95% confidence interval (CI): 0.0, 7.0), 4.2 (95% CI: 0.6, 7.9), 6.8 (95% CI: 2.0, 11.5), and 11.1 (95% CI: 2.2, 20.1) points per year slower, respectively, relative to the reference group (P = 0.003). Unadjusted hazard ratios for death by lifestyle score were as follows: for a score of 1, the hazard ratio was 0.79 (95% CI: 0.61, 1.03); for a score of 2, the hazard ratio was 0.61 (95% CI: 0.46, 0.81); for a score of 3, the hazard ratio was 0.49 (95% CI: 0.32, 0.75); and for a score of 4, the hazard ratio was 0.19 (95% CI: 0.05, 0.75) (P < 0.001 by log-rank test). In conclusion, a combination of regular exercise, healthy diet, smoking avoidance, and weight maintenance was associated with lower coronary calcium incidence, slower calcium progression, and lower all-cause mortality over 7.6 years.

Coronary artery calcium for the prediction of mortality in young adults <45 years old and elderly adults >75 years old.

AIMS: To determine if coronary artery calcium (CAC) scoring is independently predictive of mortality in young adults and in the elderly population and if a young person with high CAC has a higher mortality risk than an older person with less CAC. METHODS AND RESULTS: We studied a cohort of 44 052 asymptomatic patients referred for CAC scans for cardiovascular risk stratification. All-cause mortality rates (MRs) were calculated after stratifying by age groups (<45, 45-54, 55-64, 65-74, and ≥75) and CAC score (0, 1-100, 100-400, and >400). Multivariable Cox regression models were constructed to assess the independent value of CAC for predicting all-cause mortality in the <45- and ≥75-year-old age groups. The MR increased in both the <45- and ≥75-year-old age groups with an increasing CAC group. After multivariable adjustment, increasing CAC remained independently predictive of increased mortality compared with CAC = 0 [<45 age group, hazard ratio (95% confidence interval): CAC = 1-100, 2.3 (1.2-4.2); CAC = 100-400, 7.4 (3.3-16.6); CAC > 400, 34.6 (15.5-77.4); ≥75 age group: CAC = 1-100, 7.0 (2.4-20.8); CAC = 100-400, 9.2 (3.2-26.5); CAC > 400, 16.1 (5.8-45.1)]. Persons <45 years old with CAC = 100-400 and CAC > 400 had 2- and 10-fold increased MRs, respectively, compared with persons ≥75 with no CAC. Individuals ≥75 years old with CAC = 0 had a 5.6-year survival rate of 98%, similar to those in other age groups with CAC = 0 (5.6-year survival, 99%). CONCLUSION: The value of CAC for predicting mortality extends to both elderly patients and those <45 years old. Elderly persons with no CAC have a lower MR than younger persons with high CAC.

Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study.

BACKGROUND: The JUPITER trial showed that some patients with LDL-cholesterol concentrations less than 3·37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more benefit from treatment with rosuvastatin, although absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values. METHODS: 950 participants from the Multi-Ethnic Study of Atheroslcerosis (MESA) met all criteria for JUPITER entry. We compared coronary heart disease and cardiovascular disease event rates and multivariable-adjusted hazard ratios after stratifying by burden of CAC (scores of 0, 1-100, or >100). We calculated 5-year number needed to treat (NNT) by applying the benefit recorded in JUPITER to the event rates within each CAC strata. FINDINGS: Median follow-up was 5·8 years (IQR 5·7-5·9). 444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in this group, rates of coronary heart disease events were 0·8 per 1000 person-years. 74% of all coronary events were in the 239 (25%) of participants with CAC scores of more than 100 (20·2 per 1000 person-years). For coronary heart disease, the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1-100, and 24 for scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4·29 (95% CI 1·99-9·25) for coronary heart disease, and of 2·57 (1·48-4·48) for cardiovascular disease. hsCRP was not associated with either disease after multivariable adjustment. INTERPRETATION: CAC seems to further stratify risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with measurable atherosclerosis could allow for more appropriate allocation of resources. FUNDING: National Institutes of Health-National Heart, Lung, and Blood Institute.

Association between obesity, high-sensitivity C-reactive protein ≥2 mg/L, and subclinical atherosclerosis: implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however, the association of hsCRP and atherosclerosis, independent of obesity, remains unknown. METHODS AND RESULTS: We studied 6760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: nonobese/low hsCRP, nonobese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean body mass index was 28.3±5.5 kg/m(2), and median hsCRP was 1.9 mg/L (0.84 to 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independently of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2083 JUPITER-eligible individuals. CONCLUSION: High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independently of hsCRP status.

Evolving Role of Calcium Density in Coronary Artery Calcium Scoring and Atherosclerotic Cardiovascular Disease Risk.

Coronary artery calcium (CAC) is a specific marker of coronary atherosclerosis that can be used to measure calcified subclinical atherosclerotic burden. The Agatston method is the most widely used scoring algorithm for quantifying CAC and is expressed as the product of total calcium area and a quantized peak calcium density weighting factor defined by the calcification attenuation in HU on noncontrast computed tomography. Calcium density has emerged as an important area of inquiry because the Agatston score is upweighted based on the assumption that peak calcium density and atherosclerotic cardiovascular disease (ASCVD) risk are positively correlated. However, recent evidence demonstrates that calcium density is inversely associated with lesion vulnerability and ASCVD risk in population-based cohorts when accounting for age and plaque area. Here, we review calcium density by focusing on 3 main areas: 1) CAC scan acquisition parameters; 2) pathophysiology of calcified plaques; and 3) epidemiologic evidence relating calcium density to ASCVD outcomes. Through this process, we hope to provide further insight into the evolution of CAC scoring on noncontrast computed tomography.

Genetic testing for early detection of individuals at risk of coronary heart disease and monitoring response to therapy: challenges and promises.

Coronary heart disease (CHD) often presents suddenly with little warning. Traditional risk factors are inadequate to identify the asymptomatic high-risk individuals. Early identification of patients with subclinical coronary artery disease using noninvasive imaging modalities would allow the early adoption of aggressive preventative interventions. Currently, it is impractical to screen the entire population with noninvasive coronary imaging tools. The use of relatively simple and inexpensive genetic markers of increased CHD risk can identify a population subgroup in which benefit of atherosclerotic imaging modalities would be increased despite nominal cost and radiation exposure. Additionally, genetic markers are fixed and need only be measured once in a patient's lifetime, can help guide therapy selection, and may be of utility in family counseling.

Warranty Period of a Calcium Score of Zero: Comprehensive Analysis From MESA.

OBJECTIVES: This study sought to quantify and model conversion of a normal coronary artery calcium (CAC) scan to an abnormal CAC scan. BACKGROUND: Although the absence of CAC is associated with excellent prognosis, progression to CAC >0 confers increased risk. The time interval for repeated scanning remains poorly defined. METHODS: This study included 3,116 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with baseline CAC = 0 and follow-up scans over 10 years after baseline. Prevalence of incident CAC, defined by thresholds of CAC >0, CAC >10, or CAC >100, was calculated and time to progression was derived from a Weibull parametric survival model. Warranty periods were modeled as a function of sex, race/ethnicity, cardiovascular risk, and desired yield of repeated CAC testing. Further analysis was performed of the proportion of coronary events occurring in participants with baseline CAC = 0 that preceded and followed repeated CAC testing at different time intervals. RESULTS: Mean participants' age was 58 ± 9 years, with 63% women, and mean 10-year cardiovascular risk of 14%. Prevalence of CAC >0, CAC >10, and CAC >100 was 53%, 36%, and 8%, respectively, at 10 years. Using a 25% testing yield (number needed to scan [NNS] = 4), the estimated warranty period of CAC >0 varied from 3 to 7 years depending on sex and race/ethnicity. Approximately 15% of participants progressed to CAC >10 in 5 to 8 years, whereas 10-year progression to CAC >100 was rare. Presence of diabetes was associated with significantly shorter warranty period, whereas family history and smoking had small effects. A total of 19% of all 10-year coronary events occurred in CAC = 0 prior to performance of a subsequent scan at 3 to 5 years, whereas detection of new CAC >0 preceded 55% of future events and identified individuals at 3-fold higher risk of coronary events. CONCLUSIONS: In a large population of individuals with baseline CAC = 0, study data provide a robust estimation of the CAC = 0 warranty period, considering progression to CAC >0, CAC >10, and CAC >100 and its impact on missed versus detectable 10-year coronary heart disease events. Beyond age, sex, race/ethnicity, diabetes also has a significant impact on the warranty period. The study suggests that evidence-based guidance would be to consider rescanning in 3 to 7 years depending on individual demographics and risk profile.

The glycemic response is a personal attribute.

The Glycemic Index (GI) is a measure of the extent of the change in blood glucose content (glycemic response) following consumption of digestible carbohydrate, relative to a standard such as glucose. We have explored whether the reported GIs of foods are a sufficient guide to a person wishing to avoid large glycemic responses and thereby avoid hyperglycemia. For this purpose, volunteers carried out multiple tests of four foods, following overnight fasting, measuring the glycemic response over 2 H. The areas under the blood glucose/time curves (AUCs) were compared. Each food tester displayed individual, characteristic glycemic responses to each food, unrelated to any other tester's response. Wide variations (up to 5-fold) were seen between the average AUCs for the same test by different testers. The absolute magnitudes of the glycemic responses are important for individuals trying to control blood sugar and/or body weight, but using published GI lists as a guide to control the glycemic response is not fully informative. This is because in calculating the GI, individual glycemic responses to glucose are normalized to 100. GI values are, therefore, relative and are not necessarily a reliable guide to the person's actual individual AUC when consuming a food. Without knowledge of the person's characteristic blood glucose responses, reliance only on the GI may be misleading.

Effect of a two-year obesity prevention intervention on percentile changes in body mass index and academic performance in low-income elementary school children.

OBJECTIVES: We assessed the effects of a school-based obesity prevention intervention that included dietary, curricula, and physical activity components on body mass index (BMI) percentiles and academic performance among low-income elementary school children. METHODS: The study had a quasi-experimental design (4 intervention schools and 1 control school; 4588 schoolchildren; 48% Hispanic) and was conducted over a 2-year period. Data are presented for the subset of the cohort who qualified for free or reduced-price school lunches (68% Hispanic; n = 1197). Demographic and anthropometric data were collected in the fall and spring of each year, and academic data were collected at the end of each year. RESULTS: Significantly more intervention than control children stayed within normal BMI percentile ranges both years (P = .02). Although not significantly so, more obese children in the intervention (4.4%) than in the control (2.5%) decreased their BMI percentiles. Overall, intervention schoolchildren had significantly higher math scores both years (P < .001). Hispanic and White intervention schoolchildren were significantly more likely to have higher math scores (P < .001). Although not significantly so, intervention schoolchildren had higher reading scores both years. CONCLUSIONS: School-based interventions can improve health and academic performance among low-income schoolchildren.

Cor triatriatum sinister in an adult: management guided by real time three-dimensional transesophageal echocardiography and stress echocardiography.

A 39-year-old female had cor triatriatum (CT) detected as an incidental finding on transthoracic echocardiography performed to evaluate chest pain. By conventional two- and real time three-dimensional transesophageal echocardiography, the CT membrane had a communicating orifice connecting the accessory and main left atrial chambers that measured 1.3 × 0.8 cm. The resting mean transmembrane gradient was 2 mm Hg. The postexercise mean transmembrane gradient and pulmonary artery pressure were 6 and 40 mm Hg. Extrapolating from cutoff values for postexercise gradients and pulmonary pressures in patients with mitral stenosis, we advised deferring surgery and close clinical and echocardiographic follow up.