Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial.

AIMS: Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients. METHODS AND RESULTS: A total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P < 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P < 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053). CONCLUSIONS: Icosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.

Sex Differences in Coronary Artery Calcium and Long-term CV Mortality.

PURPOSE OF REVIEW: To summarize differences in plaque depositions, coronary artery calcium (CAC) scoring, and the role of CAC in predicting atherosclerotic cardiovascular disease (ASCVD) mortality in men and women. RECENT FINDINGS: Women have coronary plaque that is more lipid-rich, dense, and less calcified than their male counterparts. CAC scoring has emerged as a useful tool to quantify ASCVD burden. However, recent evidence favors the use of sex-adjusted CAC cutoffs for women to account for the relatively lower overall CAC burden and therefore risk stratify women appropriately. Several studies have identified CAC distribution patterns in women associated with increased CV mortality, particularly the number of lesions involved, CAC volume, and size. Multiple studies have shown that the pathophysiology and associated risks of ASCVD are different in women when compared with men. CAC scoring is a tool that is widely being used for ASCVD risk stratification. Recent studies have shown that although men have higher CAC burdens, women are more likely to develop plaque erosions with non-calcified plaque that carries a greater risk for cardiovascular events. Providers should be aware of sex-specific CAC patterns carrying increased mortality risk for women, particularly increasing lesion size and number. Given the differences in plaque composition and distribution, revised sex-adjusted CAC scoring is suggested to better risk stratify patients, especially those deemed intermediate risk, and decrease CV mortality.

Randomized trial of rivaroxaban versus warfarin in the evaluation of progression of coronary atherosclerosis.

Warfarin, a vitamin K antagonist, is associated with systemic vascular calcification. We evaluated whether rivaroxaban (a direct oral factor Xa inhibitor with no interaction with vitamin K) will slow the progression in coronary plaque volumes compared with warfarin in patients with nonvalvular atrial fibrillation using coronary computed tomography angiography.

A Leaky False Pouch: Left Ventricle Pseudoaneurysm with Active Hemopericardium Detected on Cardiac Computed Tomography Angiography.

Pseudoaneurysm is a rare but fatal complication of myocardial infarction (MI). With the advances in cardiovascular disease detection and treatments, fatal structural complications post-MI are now rare. When they occur, advanced diagnostic modalities can be used for early diagnosis, aiding surgical planning, and improving prognosis. In our case, post-MI left ventricle pseudoaneurysm complicated by hemopericardium was diagnosed using cardiac computed tomography angiography (CCTA). Use of attenuation measurement on CCTA helped diagnose active extravasation into the hemopericardium. This case highlights the high index of suspicion needed for rare but fatal complications post-MI and the utility of CCTA in their management.

Efficacy and Safety of Iodixanol in Computed Coronary Tomographic Angiography and Cardiac Catheterization.

Iodixanol is an iso-osmolar non-ionic dimeric hydrophilic contrast agent with a higher viscosity than the monomeric agents. It is the only Food and Drug Administration (FDA)-approved iso-osmolar agent in the United States, and it is the only contrast agent with an FDA-approved indication for use in cardiac computed tomographic angiography (CCTA), to assist in the diagnostic evaluation of patients with suspected coronary artery disease. In clinical studies, it has been noted to have fewer side effects and similar image quality when compared to low-osmolar contrast media. This can be attributed to the pharmacological properties of iodixanol. These contrast agents are used for coronary computed tomography angiography and cardiac catheterization. In this article, the use, tolerability, and efficacy of iodixanol are reviewed, specifically evaluating the use of CCTA and coronary angiography, including outcome studies, randomized trials, and comparisons to other contrast agents.

Quantitative imaging biomarkers of coronary plaque morphology: insights from EVAPORATE.

Aims: Residual cardiovascular risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total events, but the mechanisms of benefit are not fully understood. EVAPORATE evaluated the effects of IPE on plaque characteristics by coronary computed tomography angiography (CCTA). Given the conclusion that the IPE-treated patients demonstrate that plaque burden decreases has already been published in the primary study analysis, we aimed to demonstrate whether the use of an analytic technique defined and validated in histological terms could extend the primary study in terms of whether such changes could be reliably seen in less time on drug, at the individual (rather than only at the cohort) level, or both, as neither of these were established by the primary study result. Methods and Results: EVAPORATE randomized the patients to IPE 4 g/day or placebo. Plaque morphology, including lipid-rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH), was assessed using the ElucidVivo® (Elucid Bioimaging Inc.) on CCTA. The changes in plaque morphology between the treatment groups were analyzed. A neural network to predict treatment assignment was used to infer patient representation that encodes significant morphological changes. Fifty-five patients completed the 18-month visit in EVAPORATE with interpretable images at each of the three time points. The decrease of LRNC between the patients on IPE vs. placebo at 9 months (reduction of 2 mm3 vs. an increase of 41 mm3, p = 0.008), widening at 18 months (6 mm3 vs. 58 mm3 increase, p = 0.015) were observed. While not statistically significant on a univariable basis, reductions in wall thickness and increases in cap thickness motivated multivariable modeling on an individual patient basis. The per-patient response assessment was possible using a multivariable model of lipid-rich phenotype at the 9-month follow-up, p < 0.01 (sustained at 18 months), generalizing well to a validation cohort. Conclusion: Plaques in the IPE-treated patients acquired more characteristics of stability. Reliable assessment using histologically validated analysis of individual response is possible at 9 months, with sustained stabilization at 18 months, providing a quantitative basis to elucidate drug mechanism and assess individual patient response.

Blood Cancer and the Heart: Light Chain Cardiomyopathy in Refractory Multiple Myeloma.

We report a case of a 57-year-old woman with a history of multiple myeloma (MM) and light chain (AL) amyloidosis who presented due to worsening dyspnea on exertion. Her MM has been refractory to multiple chemotherapy regimens and two autologous bone marrow transplantation. Diagnostic evaluations including serum kappa and lambda chains, echocardiogram, pyrophosphate cardiac scan, and cardiac magnetic resonance were indicative of a progression to AL cardiomyopathy. Addition of daratumumab to her regimen appeared to ameliorate the progression of AL cardiomyopathy. However, it was stopped due to adverse effects of pancytopenia and allergic reactions including skin rash and hives. She was hospitalized for heart failure exacerbation and died approximately 2 months following the discontinuation of daratumumab. This case highlights the late presentation of AL cardiomyopathy in refractory MM.

Radiation Doses in Patients Undergoing Computed Tomographic Coronary Artery Calcium Evaluation With a 64-Slice Scanner Versus a 256-Slice Scanner.

Computed tomographic coronary artery calcium scanning enables cardiovascular risk stratification; however, exposing patients to high radiation levels is an ongoing concern. New-generation computed tomographic systems use lower radiation doses than older systems do. To quantify comparative doses of radiation exposure, we prospectively acquired images from 220 patients with use of a 64-slice GE LightSpeed VCT scanner (control group, n=110) and a 256-slice GE Revolution scanner (study group, n=110). The groups were matched for age, sex, and body mass index; statistical analysis included t tests and linear regression. The mean dose-length product was 21% lower in the study group than in the control group (60.2 ± 27 vs 75.9 ± 22.6 mGy·cm; P <0.001) and also in each body mass index subgroup. Similarly, the mean effective radiation dose was 21% lower in the study group (0.84 ± 0.38 vs 1.06 ± 0.32 mSv) and lower in each weight subgroup. After adjustment for sex, women in the study group had a lower dose-length product (50.4 ± 23.4 vs 64.7 ± 27.6 mGy·cm) than men did and received a lower effective dose (0.7 ± 0.32 vs 0.9 ± 0.38 mSv) (P=0.009). As body mass index and waist circumference increased, so did doses for both scanners. Our study group was exposed to radiation doses lower than the previously determined standard of 1 mSv, even after adjustment for body mass index and waist circumference. In 256-slice scanning for coronary artery calcium, radiation doses are now similar to those in lung cancer screening and mammography.

Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results.

AIMS: Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients. METHODS AND RESULTS: EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40-115 mg/dL, and persistently high triglyceride levels (135-499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (-1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use. CONCLUSION: EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial. CLINICALTRIALS. GOVIDENTIFIER: NCT029226027.

Effect of a plant-based bioequivalent inorganic nitrate (NO3-) complex with vitamins, antioxidants and phytophenol rich food extracts in hypertensive individuals - A randomized, double-blind, placebo-controlled study.

BACKGROUND: This study assessed efficacy of plant based bioequivalent nitrate complex, consist of vitamins, natural antioxidants and phytophenol rich food extracts to elevate nitric oxide (NO) bioavailability as determined by saliva conversion of nitrate (NO3-) to nitrite (NO2-) a required step to produce NO, in relationship to lowering blood pressure (BP) in both men and women. METHODS: 67 individuals (26 men; mean age of 59.3 ± 9.0 yrs) with mean baseline systolic and diastolic BP >120 and 80 mmHg respectively were randomized to receive daily dosing of 314 mM NO3- or NO3- free (placebo) tablets in double-blinded study for 12 weeks (wks). Inorganic NO3- tablets consist of NO3- rich beetroot extract, thiamine nitrate, and potassium nitrate in the presence of ascorbic acid, to facilitate NO bioavailability. RESULTS: The primary endpoint of the study was reduction in BP at 12 wks by improving endothelial function. At study conclusion, mean ± SD reduction in systolic BP (SBP) in the inorganic NO3- group was 12.5 ± 13.3 mmHg (p = 0.0007), as compared to 6.19 ± 11.39 mmHg (p = 0.004) in the placebo group, for a placebo-corrected reduction of -6.31 mmHg (95% CI 10.89-2.31, p = 0.04). NO3- also reduced diastolic BP by 4.7 ± 10.3 mmHg (p = 0.01), while no significant reduction in placebo group (1.98 ± 9.38 mmHg, p = 0.24) was noted. Endothelial function improved at 12 weeks by 0.8 ± 3.1 (p = 0.03) in active group when compared to 0.1 ± 1.8 (p = 0.82) in placebo group. CONCLUSION: Endothelial function improved robustly reducing both systolic and diastolic BP in hypertensive individuals with daily supplementation of dietary NO3-. CLINICALTRIALS. GOV ID: NCT03909789.

Association of flow mediated vasodilation and burden of subclinical atherosclerosis by coronary CTA.

BACKGROUND AND AIMS: Endothelial dysfunction and atherosclerosis are linked by multiple mechanisms. Brachial artery flow-mediated dilation (FMD) rate is used to evaluate endothelial function and has been independently associated with adverse cardiac outcomes. The relationship between brachial artery FMD rate and severity of subclinical atherosclerosis by coronary computed tomography angiography (CCTA) is not understood. We hypothesized that brachial FMD is inversely associated with burden of subclinical atherosclerosis measured by CCTA. METHODS: This is a retrospective study of 100 participants with intermediate cardiac risk and atypical symptoms to examine association between brachial artery FMD rate and surrogate markers of severity of subclinical atherosclerosis on CCTA. Multivariate linear regression analysis was used to understand the relationship between brachial artery FMD rate and markers of plaque burden on CCTA including coronary artery calcium (CAC) score, segment involvement score (SIS; total number of segments with any plaque), segment stenosis score (SSS, sum of maximal stenosis score per segment), and total plaque score (TPS, the sum of all segments plaque burden). RESULTS: 52 participants (42%) were female. Mean age of the cohort was 59.3 ± 10.4 years. After adjusting for traditional risk factors, brachial artery FMD rate was inversely associated with higher CAC, TPS, SIS and SSS (p < 0.05 for all). FMD <4.5 predicted the presence of CAC >0 and ≤ 100 most effectively, with a sensitivity of 62.2% and a specificity of 66.7%, respectively (area under the curve (AUC) of 0.5729, p = 0.0302). FMD <2.7 predicted the presence of CAC >100 most effectively, with a sensitivity of 34% and a specificity of 83% respectively (AUC of 0.6226, p = 0.0095). CONCLUSIONS: Brachial FMD is independently associated with the presence and extent of subclinical atherosclerosis on CCTA. Our findings provide more detailed evidence that mechanistically, FMD, a surrogate marker of systemic endothelial dysfunction is a correlate of atherosclerotic burden, assessed by CCTA and CAC.

Aged garlic extract reduces low attenuation plaque in coronary arteries of patients with diabetes: A randomized, double-blind, placebo-controlled study.

Several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification and non-calcified plaque (NCP) in the general population. However, its effects on plaque progression in patients with diabetes have not yet been investigated, at least to the best of our knowledge. This study investigated whether AGE reduces the coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). A total of 80 participants with DM with a median age of 57 years were prospectively assigned to consume 2,400 mg AGE/day (after completion, 37 participants) or placebo (after completion, 29 participants) orally. Both groups underwent CCTA at baseline and follow-up 365 days apart. In total, 66 participants completed the study. Coronary plaque volume, including total plaque (TP), dense calcium (DC), fibrous, fibro-fatty and low-attenuation plaque (LAP) volumes were measured based upon pre-defined intensity cut-off values using semi-automated software (QAngio CT). Changes in various plaque types were normalized to the total coronary artery length. The non-parametric Wilcoxon rank-sum test was performed to examine the differences in plaque formation between the 2 groups. No significant differences were found in the baseline characteristics between the AGE and placebo groups. Compared with the placebo group, the AGE group exhibited a statistically significant regression in normalized LAP [median and standard deviation (SD) -0.2 (18.8) vs. 2.5 (69.3), P=0.0415]. No differences were observed in TP, fibrous, or fibrofatty plaque volumes between the AGE and placebo group. On the whole, this study indicated that the %LAP change in the AGE group was significantly greater than that in the placebo group in patients with diabetes. However, further studies are warranted to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events.

Feasibility of measuring pericoronary fat from precontrast scans: Effect of iodinated contrast on pericoronary fat attenuation.

BACKGROUND: Pericoronary adipose tissue (PCAT) attenuation has been identified as a marker for cardiovascular risk. The effect of contrast enhancement on fat attenuation is unknown. We aim to compare precontrast coronary scans to postcontrast CCTA for quantification of pericoronary fat volume and attenuation. METHODS: Thin slice pre- and post-contrast studies obtained at 120 kVp, heart rate <60, with no plaque or artifact in the right coronary artery (RCA) were selected. Analysis was limited to pixels -30 Hounsfield units (HU) to -190 HU and from 10 mm to 50 mm distal to the RCA origin at a radial distance equal to the vessel diameter. A subgroup with no plaque across all coronaries was also analyzed. RESULTS: Of 119 study pairs, the average RCA diameter was highly correlated at 3.85 mm (postcontrast) and 3.84 mm (precontrast), r = 0.97, p < 0.0001. The mean attenuation of pre- and postcontrast images was also highly correlated at -87.02 ±â€¯7.15 HU and -82.74 ±â€¯6.54 HU, respectively (r = 0.65, p < 0.0001). Pericoronary fat volume in the -190 to -30 HU range was 396 mm³ lower in the post contrast versus pre-contrast, consistent with higher attenuation (less negative) voxels postcontrast (p < 0.0001). Inter- and intra-reader agreement ranged 95-100% and 90% for precontrast and 85-90% for postcontrast studies, respectively. Subgroup analysis revealed precontrast attenuation -85.59 ±â€¯7.53 HU and postcontrast -82.21 ±â€¯7.15 HU were highly correlated r = 0.67, p < 0.0001. CONCLUSION: Pericoronary fat enhances with iodinated contrast, potentially explaining some of its risk-predictive capabilities. Fat attenuation and volume can be reliably measured from precontrast calcium scans, with volume quantification showing particularly strong correlation. Excellent inter- and intra-reader agreement is also demonstrated.

Association of high-density lipoprotein levels with baseline coronary plaque volumes by coronary CTA in the EVAPORATE trial.

BACKGROUND AND AIMS: Dyslipidemia with elevated triglycerides (TGL) and low high-density lipoprotein cholesterol (HDL-C) predicts residual cardiovascular risk, despite goal LDL-C levels and optimal statin therapy. Coronary plaque characterization by CCTA can provide mechanistic understanding of coronary artery disease and associated prognosis. The role of HDL-C in the pathogenesis of atherosclerosis is not well understood in statin-treated patients with elevated TGL. We sought to examine the association of HDL-C levels with baseline coronary plaque volumes, namely total plaque (TP) and total non-calcified plaque (TNCP) volumes by CCTA in participants enrolled in the EVAPORATE trial. METHODS: We analyzed 80 participants who were enrolled in the trial. Linear regression analysis as a univariate and multivariate model adjusted for significant cardiovascular risk factors was performed to evaluate independent association of HDL-C and baseline coronary plaque volumes. In an exploratory analysis, stratified by sex, we compared the association of serum HDL-C levels with baseline coronary plaque volumes in males and females. RESULTS: Mean (SD) age of participants (n = 80) was 57.1 (8.6) years and 43% were male. Median (Inter Quartile Range/IQR) log-TNCP volume was 83.0 (0.1-7.3) mm3 and median (IQR) log-TP volume was 144.8 (0.1-7.1) mm3. After adjustment for relevant clinical covariates including age, gender, BMI, hypertension, diabetes, past smoking and baseline TGL levels, increasing levels of HDL-C remain independently associated with lower baseline log-TNCP volumes (ß: 0.043 ± 0.021, p = 0.042) and baseline log-TP volumes (ß: 0.046 ± 0.022, p = 0.035) on CCTA. On stratifying by sex in a multivariable regression analysis, HDL-C levels were inversely associated with baseline log-TNCP volumes (ß: 0.066 ± 0.026, p = 0.018) and log-TP volumes (ß: 0.077 ± 0.025, p = 0.004) in females, but not in males (log-TNCP volumes ß: 0.038 ± 0.034, p = 0.282) and log-TP volumes (ß: -0.033 ± 0.036, p = 0.364). CONCLUSIONS: In a cohort of statin treated patients with known atherosclerosis and residually elevated TGL, there was a significant inverse relationship between HDL-C levels and baseline coronary plaque, TP and TNCP volumes on CCTA. Our findings provide more detailed mechanistic evidence regarding the protective role of HDL-C in coronary atherosclerosis in a high-risk cohort. Further investigation to evaluate the interaction of HDL-C levels and coronary plaque volumes on differential CVD risk in statin-treated patients with elevated TGL levels is warranted.

Aged garlic extract reduces left ventricular myocardial mass in patients with diabetes: A prospective randomized controlled double-blind study.

Increased left ventricular myocardial mass (LVM) is a well known prognostic marker of poor cardiac outcomes. Decreases in LVM have been shown to decrease the cardiovascular risk. Aged garlic extract (AGE) has been shown to have an overall favorable effect on cardiac health; however, to the best of our knowledge, no study to date has specifically examined its effects on left ventricular mass. This study investigated whether AGE can affect LVM measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). This is a double-blind, placebo controlled randomized trial. In total, 65 participants with DM with a mean age of 58 years were prospectively assigned to consume 2,400 mg AGE/day or the placebo orally. Both groups underwent CCTA at baseline and follow-up at 1 year apart. LVM was measured using automated software. The baseline characteristics did not differ between the AGE and placebo groups. There was a trend towards a significant reduction in LVM at follow-up as compared to baseline in the AGE group (119.30±34.77 vs. 121.0±34.70, P=0.059). No change was observed in LVM in the placebo group at 1-year follow-up as compared to baseline (124.6±37.33 vs. 124.6±35.13, P=0.9). On the whole, this study indicated that AGE may decrease or stabilize LVM. Further studies however, with a larger sample size and longer follow-up times are required to evaluate the effects of AGE on hypertension and LVM.

Low short-term and long-term cardiovascular and all-cause mortality in absence of coronary artery calcium: A 22-year follow-up observational study from large cohort.

OBJECTIVES: We sought to evaluate the gender-specific predictive value of coronary artery calcium (CAC) score on all-cause mortality and cardiovascular disease (CVD) mortality in individuals with and without diabetes mellitus (DM). BACKGROUND: CAC score is a robust predictor of CVD and all-cause mortality during long-term follow-up in large cohorts in adults with DM. However, less is known about its sex-specific impact on all-cause mortality in DM. METHODS: We evaluated 25,563 asymptomatic participants with no known history of coronary artery disease (CAD) who underwent clinically indicated CAC. 1999 (7.8%) individuals had diabetes. CAC was characterized as an Agatston score of 0, 1-99, 100-300, and ≫300. We evaluated the association between CAC and all-cause mortality and CVD mortality. RESULTS: Overall, 1345 individuals died (5.3%) from all causes during a mean follow-up of 14.7 ±â€¯3.8 years. CAC score was 0 in 57.5% females and 34.4% of males without DM, while 36.6% females and 20.3% males with DM had CAC-0. The frequency of CAC ≫ 300 was 18% and 36% in females and males with DM, respectively. CAC score of zero was associated with low all-cause mortality event rate in females and males with diabetes (1.7 and 2.5 events per 1000 person-years, respectively). Cardiovascular mortality per 1000 person years was ≪1 in females and males with CAC score of 0 irrespective of their diabetes. Adjusted multivariable analysis, compared to CAC-0, HR for all-cause mortality associated with CAC 1-99, 100-299 and ≫300 were 1.74(95% CI 0.65, 4.63, P-0.20), 5.54(95% CI 2.16, 14.22, P ≪ 0.001) and 5.75(95% CI 2.30, 14.37, P ≪ 0.001) in females with DM respectively; in males with DM HR associated with CAC 1-99, 100-299 and ≫300 were 1.87(95% CI 0.95, 3.66, P-0.06), 2.15(95% CI 1.05, 4.38, P-0.035) and 2.60(95% CI 1.34, 5.0, P-0.004), respectively. CONCLUSION: Presence of subclinical atherosclerosis varies among individuals with DM. The absence of CAC was associated with very low cardiovascular as well as all-cause mortality events in all subgroups during long term follow-up.

Calcification of the heart: mechanisms and therapeutic avenues.

INTRODUCTION: Coronary artery calcification (CAC) is reflective of atherosclerotic disease and incrementally predictive of future cardiovascular events (CVE), independent of traditional risk factors. Extra coronary calcium such as aortic valve calcification, which can be identified and quantified by computed tomography (CT) imaging, has shown to predict future CVE in both asymptomatic and symptomatic (i.e. stable angina and acute coronary syndrome [ACS]) settings. It has hence been a vital tool in studies involving new therapies for cardiovascular disease. Areas covered: In this review, promising therapies on the horizon are reviewed, along with the role of cardiac CT and coronary calcification in these studies. A Medline search for peer-reviewed publications using keywords related to coronary calcium score, aortic valve calcium, and therapies targeting the same was carried out. Expert commentary: CT scanning provides a distinct means of detecting and quantifying coronary plaque as well as valvular calcification with excellent reproducibility. Based on voluminous data available, the absence of coronary calcium serves as a factor to de-risk patients for cardiovascular risk stratification and management algorithms. Newer therapies have shown to lower progression of coronary calcification, thus being beneficial in slowing progression of atherosclerotic disease. As British Epidemiologist Geoffrey Rose states, the best predictor of a life-threatening disease is the early manifestation of that disease. As CAC represents the early manifestation of atherosclerosis, it is the best-known stratifier of risk today, and its clinical use will continue to rise.