Objectives

This study examines whether the coronary artery calcium (CAC) score can be used to define the target population to treat with a polypill.

Background

Prior studies have suggested a single polypill to reduce cardiovascular disease (CVD) at the population level.

Methods

Participants from MESA (Multi-Ethnic Study of Atherosclerosis) were stratified using the criteria of 4 polypill studies (TIPS [The Indian Polycap Study], Poly-Iran, Wald, and the PILL [Program to Improve Life and Longevity] Collaboration). We compared coronary heart disease (CHD) and CVD event rates and calculated the 5-year number needed to treat (NNT) after stratification based on the CAC score.

Results

Among MESA participants eligible for TIPS, Poly-Iran, Wald, and the PILL Collaboration, CAC = 0 was observed in 58.6%, 54.5%, 38.9%, and 40.8%, respectively. The rate of CHD events among those with CAC = 0 varied from 1.2 to 1.9 events per 1,000 person-years, those with CAC scores from 1 to 100 had event rates ranging from 4.1 to 5.5, and in those with CAC scores >100 the event rate ranged from 11.6 to 13.3. The estimated 5-year NNT to prevent 1 CVD event ranged from 81-130 for patients with CAC = 0, 38-54 for those with CAC scores from 1 to 100, and 18-20 for those with CAC scores >100.

Conclusions

In MESA, among individuals eligible for treatment with the polypill, the majority of CHD and CVD events occurred in those with CAC scores >100. The group with CAC = 0 had a very low event rate and a high projected NNT. The avoidance of treatment in individuals with CAC = 0 could allow for significant reductions in the population considered for treatment, with a more selective use of the polypill and, as a result, avoidance of treatment in those who are unlikely to benefit.

Background

There is limited knowledge about the risk of non-alcoholic fatty liver disease (NAFLD) associated with cardiometabolic disorders in lean persons. This study examines the contribution of cardiometabolic disorders to NAFLD risk among lean individuals and compares to non-lean individuals.

Methods

We analyzed longitudinal data from 6,513 participants of a yearly voluntary routine health testing conducted at the Hospital Israelita Albert Einstein, Brazil. NAFLD was defined as hepatic ultrasound diagnosed fatty liver in individuals scoring below 8 on the alcohol use disorders identification test. Our main exposure variables were elevated blood glucose, elevated blood pressure (BP), presence of atherogenic dyslipidemia (AD, defined as the combination of elevated triglycerides and low HDL cholesterol) and physical inactivity (<150 minutes/week of moderate activity). We further assessed the risk of NAFLD with elevations in waist circumference and high sensitivity C-reactive protein (HsCRP).

Results

Over 15,580 person-years (PY) of follow-up, the incidence rate of NAFLD was 7.7 per 100 PY. In multivariate analysis adjusting for likely confounders, AD was associated with a 72% greater risk of NAFLD (IRR: 1.72 [95% CI:1.32-2.23]). Elevated blood glucose (IRR: 1.71 [95%CI: 1.29-2.28]) and physical inactivity (IRR: 1.46 [95%CI: 1.28-1.66]) were also independently associated with increased risk of NAFLD. In lean individuals, AD, elevated blood glucose and elevated BP were significantly associated with NAFLD although for elevated blood glucose, statistical significance was lost after adjusting for possible confounders. Physical inactivity and elevations in HsCRP were not associated with the risk of NAFLD in lean individuals only. Among lean (and non-lean) individuals, there was an independent association between progressively increasing waist circumference and NAFLD.

Conclusion

Cardiometabolic risk factors are independently associated with NAFLD. However, there are significant differences in the metabolic risk predictors of NAFLD between lean and non-lean individuals. Personalized cardiovascular disease risk stratification and appropriate preventive measures should be considered in both lean and non-lean individuals to prevent the development of NAFLD.

Aims

The European Society of Cardiology (ESC) guideline on cardiovascular risk assessment considers coronary artery calcium a class B indication for risk assessment. We evaluated the degree to which coronary artery calcium can change the recommendation for individuals based on a change in estimated risk.

Methods and results

We stratified 5602 MESA participants according to the ESC recommendation as: no lipid-lowering treatment recommended ( N = 2228), consider lipid-lowering treatment if uncontrolled ( N = 1686), or lipid-lowering treatment recommended ( N = 1688). We evaluated the ability of coronary artery calcium to reclassify cardiovascular risk. Among the selected sample, 54% had coronary artery calcium of zero, 25% had coronary artery calcium of 1-100 and 21% had coronary artery calcium greater than 100. In the lipid-lowering treatment recommended group 31% had coronary artery calcium of zero, while in the lipid-lowering treatment if uncontrolled group about 50% had coronary artery calcium of zero. The cardiovascular mortality rate was 1.7%/10 years in the lipid-lowering treatment if uncontrolled, and 7.0%/10 years in the lipid-lowering treatment recommended group. The absence of coronary artery calcium was associated with 1.4%/10 years in the lipid-lowering treatment if uncontrolled group and 3.0%/10 years in the lipid-lowering treatment recommended group. Compared with coronary artery calcium of zero, any coronary artery calcium was associated with significantly higher cardiovascular mortality in the lipid-lowering treatment recommended group (9.0%/10 years), whereas only coronary artery calcium greater than 100 was significantly associated with a higher cardiovascular mortality in the lipid-lowering treatment if uncontrolled group (3.2%/10 years).

Conclusion

The absence of coronary artery calcium is associated with a low incidence of cardiovascular mortality or coronary heart disease events even in individuals in whom lipid-lowering therapy is recommended. A significant proportion of individuals deemed to be candidates for lipid-lowering therapy might be reclassified to a lower risk group with the use of coronary artery calcium.

Low-dose rivaroxaban was effective in secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in the COMPASS trial. There is no established role, however, for oral anticoagulants in primary prevention. We evaluated whether coronary artery calcium (CAC) scoring identifies a high-risk primary prevention adult population who may benefit from low-dose rivaroxaban to prevent ASCVD events. We modeled expected outcomes of low-dose rivaroxaban in 5,196 Multiethnic Study of Atherosclerosis (MESA) cohort participants not already on antiplatelet or anticoagulant therapy. We applied relative risk ratios from COMPASS to absolute MESA event rates in order to estimate number needed to treat (NNT) to avoid a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, as well as number needed to harm (NNH) to cause 1 hospitalized bleed; with both NNT and NNH stratified by calculated ASCVD risk and by baseline CAC. MESA participants with CAC ≥300 had crude ASCVD event rate of 20 per 1000 patient-years, which is comparable to that observed in the COMPASS control-arm. CAC was independently associated with the composite ASCVD outcome (p <0.001 for trend). However, CAC was not independently associated with adjusted hazard ratio for hospitalized major bleeding. Predicted 5-year NNT (modeled from COMPASS) was 75 in persons with CAC 100-299 and 45 with CAC ≥300 despite NNH values of 252 and 98, respectively. In conclusion, CAC helps to distinguish estimated ASCVD benefit from estimated bleeding harm, thereby identifying very high-risk primary prevention adults without established cardiovascular disease who may derive net-benefit from low-dose rivaroxaban.

Background

The use of non-contrast cardiac computed tomography measurements to predict heart failure (HF) has not been studied. In the present study we evaluated the prognostic value of left ventricular area adjusted for the body surface area (LVA-BSA) measured by non-contrast cardiac CT to predict incident HF and cardiovascular disease (CVD) events.

Methods

We studied left ventricular dimensions and calculated LVA-BSA in 6781 participants of the MESA study (mean age: was 62 ± 10 years, 53% females; 62% non-white) free from prior HF who underwent non-contrast cardiac CT to evaluate the coronary artery calcium score (CAC) at baseline and were followed up for a median of 10.2 years.

Results

During follow up, 237 (3.5%) incident HF and 475 (7.0%) CVD events occurred. After adjustment for clinical variables and CAC, LVA-BSA was significantly associated with incident HF (hazard ratio [HR]: 1.10 per 100 mm²/m², p < 0.001) and CVD events (HR: 1.07 per 100 mm²/m², p < 0.001). The area under the ROC curve for the prediction of incident HF improved from 0.787 on a model including only risk factors to 0.798 when CAC was added (p = 0.02), and to 0.816 with the additional inclusion of LVA-BSA (p = 0.007). Similar improvements for the prediction of CVD events were noted.

Conclusion

In an ethnically diverse population of asymptomatic individuals free from baseline CVD or HF, the left ventricular area measured by non-contrast cardiac CT is a strong predictor of incident HF events beyond traditional risk factors and CAC score.

Introduction

The prevalence of cardiovascular disease (CVD) is rising in Sub-Saharan Africa, but it is not known whether current risk assessment tools predict coronary atherosclerosis in the region. Furthermore, sex-specific performance and interaction with HIV serostatus has not been well studied.

Methods

This cross-sectional study compared ASCVD risk scores and detectable coronary artery calcium (CAC>0) by sex in Kampala, Uganda (n = 200). The cohort was enriched for persons living with HIV, and all participants had at least one CVD risk factor. We fit log binomial regression models and constructed ROC curves to assess the correlation between ASCVD scores and CAC>0.

Results

The mean age was 56. 62% were female and 50% of both men and women were living with HIV. The median 10-year ASCVD risk score was significantly higher in men (11.0%, IQR 7.6-19.4%) than in women (5.1%, IQR 3.2-8.7%), although the prevalence of CAC>0 was similar (8.1 vs 10.5%, p = 0.63). Each 10% increase in ASCVD risk was associated with increased risk of CAC>0 in men (PR 1.59, 95% CI 1.00-2.55, p = 0.05) but not women (PR 1.15, 95% CI 0.44-3.00, p = 0.77). ROC curves demonstrated an AUC of 0.57 for women vs 0.70 for men. Adjustment for HIV serostatus improved the predictive value of ASCVD in women only (AUC 0.78, p = 0.02).

Conclusions

ASCVD risk score did not correlate with the presence of CAC in women. When HIV status was added to the ASCVD risk score, correlation with CAC was improved in women but not in men.

Background

The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines have significantly broadened the scope of candidates eligible for statin therapy.

Objectives

This study evaluated the implications of the absence of coronary artery calcium (CAC) in reclassifying patients from a risk stratum in which statins are recommended to one in which they are not.

Methods

MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6,814 men and women 45 to 84 years of age without clinical atherosclerotic cardiovascular disease (ASCVD) risk at enrollment. We excluded 1,100 participants (16%) on lipid-lowering medication, 87 (1.3%) without low-density lipoprotein levels, 26 (0.4%) with missing risk factors for calculation of 10-year risk of ASCVD, 633 (9%) >75 years of age, and 209 (3%) with low-density lipoprotein <70 mg/dl from the analysis.

Results

The study population consisted of 4,758 participants (age 59 ± 9 years; 47% males). A total of 247 (5.2%) ASCVD and 155 (3.3%) hard coronary heart disease events occurred over a median (interquartile range) follow-up of 10.3 (9.7 to 10.8) years. The new ACC/AHA guidelines recommended 2,377 (50%) MESA participants for moderate- to high-intensity statins; the majority (77%) was eligible because of a 10-year estimated ASCVD risk ≥7.5%. Of those recommended statins, 41% had CAC = 0 and had 5.2 ASCVD events/1,000 person-years. Among 589 participants (12%) considered for moderate-intensity statin, 338 (57%) had a CAC = 0, with an ASCVD event rate of 1.5 per 1,000 person-years. Of participants eligible (recommended or considered) for statins, 44% (1,316 of 2,966) had CAC = 0 at baseline and an observed 10-year ASCVD event rate of 4.2 per 1,000 person-years.

Conclusions

Significant ASCVD risk heterogeneity exists among those eligible for statins according to the new guidelines. The absence of CAC reclassifies approximately one-half of candidates as not eligible for statin therapy.

Objectives

The aim of this study was to assess the odds of initiation or continuation of pharmacological and lifestyle preventive therapies in patients with nonzero versus zero coronary artery calcium (CAC) score detected on cardiac computed tomography.

Background

Detection of calcified coronary plaque could serve as a motivational tool for physicians and patients to intensify preventive therapies.

Methods

We searched PubMed, EMBASE (Excerpta Medica database), Web of Science, Cochrane CENTRAL (Cochrane central register of controlled trials), ClinicalTrials.gov, and the International Clinical Trials Registry Platform for studies evaluating the association of CAC scores with downstream pharmacological or lifestyle interventions for prevention of cardiovascular disease. Pooled odds ratios (ORs) of downstream interventions were obtained using the DerSimonian and Laird random effects model.

Results

After a review of 6,256 citations and 54 full-text papers, 6 studies (11,256 participants, mean follow-up time: 1.6 to 6.0 years) were included. Pooled estimates of the odds of aspirin initiation (OR: 2.6; 95% confidence interval [CI]: 1.8 to 3.8), lipid-lowering medication initiation (OR: 2.9; 95% CI: 1.9 to 4.4), blood pressure-lowering medication initiation (OR: 1.9; 95% CI: 1.6 to 2.3), lipid-lowering medication continuation (OR: 2.3; 95% CI: 1.6 to 3.3), increase in exercise (OR: 1.8; 95% CI: 1.4 to 2.4), and dietary change (OR: 1.9; 95% CI: 1.5 to 2.5) were higher in individuals with nonzero CAC versus zero CAC scores, but not for aspirin or blood pressure-lowering medication continuation. When assessed within individual studies, these findings remained significant after adjustment for baseline patient characteristics and cardiovascular risk factors.

Conclusions

This systematic review and meta-analysis suggests that nonzero CAC score, identifying calcified coronary plaque, significantly increases the likelihood of initiation or continuation of pharmacological and lifestyle therapies for the prevention of cardiovascular disease.

BACKGROUND:Morphometric measurements of systemic atherosclerosis and direct quantification of visceral fat are only possible using materials from autopsy studies. However, the few autopsy studies that have investigated the association of visceral fat with atherosclerosis had small sample sizes and focused on coronary arteries of young or middle-aged White subjects. We aimed to investigate the association of pericardial fat (PF) and abdominal visceral fat (AVF) with atherosclerosis in the aorta, coronary, carotid, and cerebral arteries in a large autopsy study. MATERIALS AND METHODS:We evaluated deceased subjects aged 30 years or above. We dissected and weighted the PF and the AVF and evaluated the atherosclerotic burden in the aorta, as well as the carotid, coronary, and cerebral arteries using morphometric measurements. We also investigated the interaction of PF and AVF with age regarding the atherosclerotic burden. RESULTS:The mean age of the 240 included subjects was 64.8±15.3 years, and 63% was male. Greater PF was associated with a higher degree of aortic atherosclerosis after adjusting for confounding variables (coefficient = 4.39, 95% CI = 0.83; 7.94, p = 0.02). Greater AVF was associated with a higher coronary stenosis index (coefficient = 1.49, 95% CI = 0.15; 2.83, p = 0.03) and a greater number of coronary plaques (coefficient = 0.71, 95% CI = 0.24; 1.19, p = 0.003). We did not find an association of PF or AVF with carotid or cerebral atherosclerotic burden. We found a significant interaction of AVF (coefficient = -0.08; 95% CI = -0.14; -0.02, p = 0.009) and PF (coefficient = -0.87, 95% CI = -1.70; -0.04, p = 0.04) with age regarding carotid artery atherosclerotic burden. CONCLUSIONS:Greater AVF was associated with greater atherosclerotic burden and extent in coronary arteries, while greater PF correlated with a higher degree of atherosclerosis in the aorta.

Background Macrophages and T lymphocytes in the perivascular adipose tissue (PvAT) were previously linked to coronary artery disease. However, the role of these cells and B lymphocytes in the human PvAT adjacent to unstable atherosclerotic plaques has not been investigated. Moreover, previous studies were inconclusive on whether PvAT inflammation was restricted to the surroundings of the atheroma plaque. Methods and Results Coronary arteries were freshly dissected with the surrounding PvAT. Atherosclerotic plaques were classified according to the internationally accepted anatomopathological criteria. Immune cells in the PvAT were detected using immunohistochemistry and then quantified. We used linear and logistic regressions with robust standard errors, adjusted for possible confounding factors. In 246 atherosclerotic plaques (205 stable and 41 unstable plaques) from 82 participants (mean age=69.0±14.4 years; 50% men), the percentage of arterial obstruction was positively correlated with the densities of CD68⁺ macrophages (P=0.003) and CD20⁺ B lymphocytes (P=0.03) in the periplaque PvAT. The number of cells was greater in the periplaque PvAT than in the distal PvAT (macrophages, P<0.001; B lymphocytes, P=0.04). In addition, the density of macrophages in the periplaque PvAT was greater in the presence of unstable plaques (P=0.03) and was also greater near unstable plaques than in the distal PvAT (P=0.001). CD3⁺ T lymphocytes were not associated with percentage of obstruction and stable/unstable plaque composition. Conclusions The density of CD20⁺ B lymphocytes and CD68⁺ macrophages in periplaque PvAT was increased with plaque size, and the CD68⁺ macrophages were greater near unstable atherosclerotic plaques than near stable lesions. This inflammation was more intense in the periplaque PvAT than in the PvAT distal to the atherosclerotic plaques.