Calcium score of the entire thoracic aorta is an independent predictor of all-cause mortality in patients referred to chest computed tomography.

BACKGROUND: Thoracic arterial calcifications (TAC) are not routinely reported or quantified in chest CT scans. We aimed to evaluate the association between TAC of the entire thoracic aorta and all-cause mortality (ACM) in patients referred to standard chest CT. METHODS: A retrospective analysis of consecutive standard chest CT scans (non-gated, non-contrast) for the quantification of TAC, CAC and aortic valve calcification. TAC was divided into 4 sample-derived categories (TAC 1 = 0, TAC 2 = 1-65, TAC 3 = 66-439 and TAC 4 ≥ 440). Data regarding ACM was retrieved from the health care provider database. Multivariate Cox proportional regression models were used to assess associations between the TAC categories and ACM. RESULTS: The study cohort included 415 patients (mean age 67 years, 52% male); 107 ACM events were recorded during a median follow-up of 9 years (inter-quartile range: 7.4-10.4). The rate of ACM was 13%, 25%, 32%, 41% according to TAC category (p < 0.001). The highest TAC category (≥ 440) was a strong and independent predictor of ACM [HR = 1.69 (1.13-2.52; 0.01)] in multivariate analysis. Other independent predictors of ACM included age [HR = 1.07 (1.04-1.10; p < 0.001)], male sex [HR = 2.27 (1.49-3.46; 0.001)] and malignancy [HR = 2.21 (1.49-3.23; < 0.001)]. CONCLUSIONS: Severe TAC (≥ 440) was found to be an independent predictor of ACM. Thus, we suggest that documenting and quantifying TAC should be routinely incorporated into standard chest CT reports.

The Multi-Ethnic Study of Atherosclerosis-Calcium Score Improves Statin Treatment Allocation in Asymptomatic Adults.

Background: The current categorization of cardiovascular (CV) risk broadens the indications for statin therapy. Coronary artery calcium (CAC) identifies those who are most likely to benefit from primary prevention with statin therapy. The multi-ethnic study of atherosclerosis-calcium (MESA-C) includes CAC for CV risk stratification. Objective: We aimed to establish whether the MESA-C score improves allocation to statin treatment in a cohort of asymptomatic adults. We also analyzed patient survival according to their risk score calculation. Design: A retrospective analysis of asymptomatic adults. Participants: A total of 632 consecutive subjects free of coronary artery disease (CAD) and/or stroke, mean age 56 ± 7 years, 84% male, underwent clinical evaluations and CAC measurements. Main Measures: PCE and MESA-C risk scores were calculated for each subject. According to the 10-year risk for CV events, subjects were classified into moderate and high CV risk (≥7.5%) for whom a statin is clearly indicated, or borderline and low CV risk (<7.5%). Key Results: During mean follow-up of 6.5 ± 3.3 years, 52 subjects experienced their first CV event. Those with a MESA-C risk score < 7.5% had favorable outcomes even when the PCE indicated a risk of ≥ 7.5%. The MESA-C score improved the discrimination of CV risk with the ROC curves C-statistics increasing from 0.653 for the PCE to 0.770 for the MESA-C. Of those, 84% (99/118) with borderline CV risk (5-7.5%) according to the PCE score, were reallocated by the MESA-C score into a higher (≥7.5%) or lower (<5%) CV risk category. Furthermore, subjects with low MESA-C scores had the highest survival rate regardless of the PCE risk, while those with high MESA-C risks had the lowest survival rate regardless of the PCE risk. Conclusion: In asymptomatic subjects, the MESA-C score improves allocation to statin treatment and CV risk discrimination, while both scores are essential for more precise survival estimations.

Combined aortic valve and coronary artery calcifications in lung cancer screening as predictors of death from cardiovascular disease.

OBJECTIVES: Smoking is a major risk factor for both cardiovascular disease (CVD) and lung cancer. Aortic valve calcification (AVC) and coronary artery calcification (CAC) are both due to atherosclerotic disease. We aim to investigate whether AVC on low-dose CT (LDCT) predicts death from CVD in smokers beyond that provided by CAC. METHODS: We reviewed a prospective cohort of 8618 smokers enrolled in LDCT screening for lung cancer in New York State between June 2000 and December 2005. As of December 2009, 169 of the 643 deaths were due to CVD; median follow-up time was 96.4 months. Visual AVC was assessed as being absent (AVC = 0) or present (AVC > 0). CAC ordinal scores of 0-12 were categorized into three validated prognostic categories (0, 1-3, and 4-12). Cox proportional hazards regression analysis was used to assess whether AVC > 0 increased the risk of CVD death, after adjustment for CAC categories and other risk factors. RESULTS: The prevalence of AVC significantly increased (p < 0.0001) with the increasing severity of the CAC categories; Pearson, Spearman, and Kendall's correlation coefficients showed a significant correlation between AVC and CAC with r = 0.29, ρ = 0.32, and τB = 0.28 (all p values < 0.0001), respectively. CAC and AVC were significant predictors of CVD death when considered alone using multivariable Cox regression analysis (adjusted HR of CAC = 1.57, p = 0.04; adjusted HR of AVC = 1.39, p = 0.045). When AVC > 0 and CAC ≥ 4, the hazard ratio was 2.35 (95%CI 1.57-3.50) compared with the reference group of AVC = 0 and CAC < 4, when adjusted for other risk factors. CONCLUSIONS: The presence of AVC identified on LDCT is a significant predictor of future CVD death, particularly for those with ordinal CAC score ≥ 4. KEY POINTS: • Aortic valve calcification (AVC) and coronary artery calcification (CAC) are both due to atherosclerotic disease. The prevalence of AVC in lung cancer screening cohort significantly increased with the increasing severity of CAC. • CAC and AVC were significant predictors of cardiovascular disease (CVD) death when considered alone. Participants who underwent lung cancer screening with AVC > 0 and CAC ≥ 4 had more than a 2-fold increased risk of CVD death than the group with AVC = 0 and CAC < 4, when adjusted for other risk factors.

Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe.

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39-61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the "Initiative for European Lung Screening (IELS)"-a large international group of physicians and other experts concerned with lung cancer-agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached.

[ENDOTHELIAL DYSFUNCTION: A POSITION PAPER OF THE ISRAEL HEART SOCIETY].

INTRODUCTION: Prediction of cardiovascular adverse events is challenging. It became apparent that traditional coronary artery disease (CAD) risk factors are the cornerstones of the European 10-year CAD risk SCRORE and the Framingham score. However, despite their importance, the prediction value of general assessment tools such as the SCORE and Framingham options in an individual subject is limited, especially in young adults and women. The trend toward personalized medicine and individualized risk assessment during recent years is growing strong and various functional and imaging screening tests, including endothelial function studies, have been suggested to improve accuracy and provide the functional implications of these risk factors. Endothelial dysfunction is an early stage of atherosclerosis and has been associated with adverse cardiovascular outcome events, including myocardial infarction, stroke and death. The purpose of this position paper is to review the scientific background, methods available for assessment of endothelial function and the interpretation of test results. The current manuscript also suggest some meaningful clinical guidelines on potential integration of these tests into our practice.

Left Ventricular Hypertrophy Predicts Cardiovascular Events in Hypertensive Patients With Coronary Artery Calcifications.

BACKGROUND: Coronary artery calcification (CAC) is associated with increased cardiovascular (CV) risk. Left ventricular hypertrophy (LVH) is an independent risk factor for CV events. Our aim was to estimate the relative CV risk of LVH in the presence of CAC. METHODS: We included asymptomatic hypertensive patients who were enrolled in the calcification arm of the INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy). Patients had baseline echocardiography and computed tomography to assess CAC. The primary end-point was the first CV event. RESULTS: Two hundred and fifty-two subjects (mean age 64.7 ± 5.5 years, 54% men) were followed for a mean of 13.3 ± 2.6 years. 72 patients (28.5%) had LVH and 159 patients (63%) had CAC. During follow up, 89 patients had a first CV event. The rate of CV events was higher in those with than in those without CAC (43.4% vs. 21.5%, P < 0.01) and in those with than in those without LVH (44% vs. 31.6%, P < 0.01). However, LVH had no effect on CV events in the absence of CAC, whereas LVH almost doubled the rate of CV events (61.4% vs. 36.5%, P < 0.01) in the presence of CAC. In comparison to patients without CAC and without LVH the hazard ratio for CV event in those with LVH was 1.46 (95% confidence interval [CI], 0.50-4.21) in those without CAC and 4.4 (95% CI, 2.02-9.56) in those with CAC. CONCLUSIONS: LVH and CAC independently predict CV events in asymptomatic hypertensive patients. However, the risk of LVH is mainly observed in those with CAC.

The Association of Secondhand Tobacco Smoke and CT Angiography-Verified Coronary Atherosclerosis.

OBJECTIVES: The aim of this study was to assess the relationship of the extent of atherosclerosis on coronary computed tomographic angiography to the extent of secondhand tobacco smoke (SHTS) exposure in asymptomatic never smokers. BACKGROUND: A dose-related association between SHTS and coronary artery calcium has been reported, but the total extent of atherosclerosis has not been investigated. METHODS: A total of 268 never smokers, ages 40 to 80 years, completed a questionnaire assessing risk factors and extent of lifetime SHTS exposure, providing a total SHTS exposure score. Ordinal coronary artery calcium scores were derived from low-dose nongated computed tomographic scans, followed by computed tomographic angiography. Analyses of the prevalence, extent, and plaque characteristics of atherosclerosis were performed, and the independent contribution of SHTS, adjusted for other documented risk factors, was determined. RESULTS: Coronary atherosclerosis was noted in 48% and was more frequent with low to moderate and high versus minimal SHTS exposure (48% and 69% vs. 25%; p < 0.0001). Adjusted odds ratios for any atherosclerosis were 2.1 (95% confidence interval: 1.0 to 4.4; p = 0.05) for low to moderate and 3.5 (95% confidence interval: 1.4 to 8.5; p = 0.01) for high exposure versus minimal SHTS exposure and were not significant for standard risk factors of diabetes (p = 0.56), hyperlipidemia (p = 0.11), hypertension (p = 0.65), and renal disease (p = 0.24). With increasing SHTS exposure, the percentage of major vessel (14%, 41%, and 45%; p = 0.0013) with any plaque or stenosis increased, as did the number with 5 or more involved segments (0%, 39%, and 61%; p = 0.0001). Also the average number of involved segments increased (0.82, 1.98, and 3.49; p < 0.0001), with calcified plaques alone (0.25, 0.77, and 1.52; p < 0.0001), with calcified and partially calcified plaques (0.28, 0.82, and 1.58; p < 0.001), but not with noncalcified plaques alone (p = 0.11). CONCLUSIONS: The presence and extent of atherosclerosis were associated with the extent of SHTS exposure even when adjusted for other risk factors, further demonstrating the causal relationship of SHTS exposure and coronary disease.

Coronary artery calcification in clinical practice: what we have learned and why should it routinely be reported on chest CT?

The recent acceptance of low dose chest computed tomography (LDCT) as a screening modality for early lung cancer detection will significantly increase the number of LDCT among high risk population. The target subjects are at the same time at high risk to develop cardiovascular (CV) events. The routine report on coronary artery calcification (CAC) will therefore, enhances the screening benefit by providing the clinicians with an additive powerful risk stratification tool for the management or primary prevention of CV events. This review will provide the radiologists with helpful information for the daily practice regarding on what is CAC, its clinical applications and how to diagnose, quantify and report on CAC while reading the LDCT.

[ISRAELI GUIDELINES FOR THE TREATMENT OF HYPERLIPIDEMIA - 2014 UPDATE].

Atherosclerosis is one of the leading causes of morbidity and mortality in the world, including in Israel. This document updates the clinical recommendations of the Israeli medical societies (The Society for Research, Prevention and Treatment of Atherosclerosis, The Israel Heart Society, The Israel Association of Family Physicians, The Israel Society of Internal Medicine) from 2012. The need for an update stems from new studies and from the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. These recommendations take into account the guidelines of leading medical organizations in the world, as well as the specific circumstances and needs of the medical system in Israel.

Coronary artery calcification on low-dose computed tomography: comparison of Agatston and Ordinal Scores.

OBJECTIVE: To compare Agatston with Ordinal Scores for the extent of coronary artery calcification (coronary artery calcium) using nongated low-dose computed tomography (CT) scans. MATERIALS AND METHODS: A total of 631 asymptomatic participants had CT scans from 2010 to 2013. Their Ordinal and Agatston Score were classified into categories. RESULTS: The Ordinal Score Categories showed excellent agreement (weighted kappa of 0.83; 95% confidence interval: 0.79-0.88) with the Agatston Score Categories. CONCLUSIONS: The use of the Ordinal Score is readily obtained on low-dose CT scans that are used for CT screening for lung cancer and these scores are useful for risk stratification of coronary artery disease.

Coronary artery calcium and exercise electrocardiogram as predictors of coronary events in asymptomatic adults.

Early identification of patients at risk for coronary heart disease is crucial to formulate effective preventive strategies. The elevated risk of coronary artery calcium (CAC) for coronary heart disease is well established. Our aim was to estimate the relative risk of abnormal exercise electrocardiography (Ex ECG) in the presence of CAC. During the year 2001, 566 asymptomatic subjects performed a treadmill exercise test and consented to perform an unenhanced computed tomography to assess CAC. Patients were followed until December 2012. The relative risk for coronary events (acute myocardial infarction, hospitalization for unstable angina or coronary catheterization that resulted in angioplasty or coronary artery bypass surgery), of abnormal Ex ECG and presence of CAC were analyzed. An abnormal Ex ECG was found in 71 subjects (12.5%), and CAC was found in 286 subjects (50.5%). During a mean follow-up of 6.5 ± 3.3 years, 35 subjects experienced a first coronary event. In those without CAC, the rate of coronary events was low (4 of 280; 1.4%) regardless of the Ex ECG results. Subjects with both CAC and abnormal Ex ECG had the highest rate of coronary events (13 of 39; 33%). The adjusted hazard ratio for coronary events, in subjects with CAC, was 5.16 (95% confidence interval 2.52 to 10.60) in those with abnormal Ex ECG compared with those with normal Ex ECG. In conclusion, in subjects with CAC, further risk stratification can be achieved by an Ex ECG, whereas in those without CAC, an Ex ECG has less additional value in predicting coronary events.

Serum uric acid is associated with coronary artery calcification.

Uric acid (UA) is associated with atherosclerosis, and coronary artery calcium (CAC) is a marker of atherosclerosis. The authors studied the association between UA and CAC. A total of 663 asymptomatic patients (564 men; mean age, 55±7 years) were evaluated for the presence of CAC. The study population was divided into three tertiles according to their UA levels, and the prevalence of CAC was compared between the tertiles. CAC was detected in 349 (53%) patients. Levels of UA were significantly higher in those with CAC than in those without CAC (5.6+1.2 vs 5.3+1.3; P=.003). The odds ratio for the presence of CAC in the highest vs lowest UA tertile was 1.72 (95% confidence interval, 1.17-2.51). The highest UA tertile remained associated with the presence of CAC after adjustment for known cardiovascular risk factors. The results show that high serum UA levels are associated with the presence of CAC.

Exaggerated blood pressure response to exercise is not associated with masked hypertension in patients with high normal blood pressure levels.

The association between exaggerated blood pressure (BP) response to exercise (ExBPR) and "masked hypertension" is unclear. Medical records of patients with high-normal BP who were evaluated in the Chaim Sheba Screening Institute Ramat Gan, Israel, during the years 2002-2007 and referred for 24-hour ambulatory BP monitoring (ABPM) and exercise test were reviewed. Data on exercise tests performed in the preceding 5 years were retrieved. Reproducible ExBPR was defined when it was recorded at least twice. BP levels on 24-hour ABPM were compared between patients with a normal BP response and those with an ExBPR (systolic BP ≥200 mm Hg). Sixty-nine normotensive patients with high normal BP levels were identified. ExBPR was recorded in 43 patients and was reproducible in 28. BP levels on 24-hour ABPM were similar in patients with and without ExBPR. In patients with high-normal BP levels, ExBPR is not associated with masked hypertension.

Bezafibrate treatment is associated with a reduced rate of re-hospitalization in smokers after acute coronary syndrome.

BACKGROUND: Significantly increased rate of hospitalizations in current smokers is a major smoking-related problem which is associated with a heavy economic burden, whereas cardiovascular disease accounted for nearly half of hospitalizations. The effect of bezafibrate on the rate of re-hospitalization in smokers already treated with statin immediately post-acute coronary syndrome (ACS) is unknown. The aim of this study was to investigate 30-day rate of re-hospitalization in current smokers participating in the ACS Israeli Surveys (ACSIS) and who were treated on discharge with a bezafibrate/statin combination vs. statin alone. METHODS: The study population comprised 3392 patients with confirmed current smoking status from the ACSIS 2000, 2002, 2004, 2006, 2008 and 2010 enrollment waves who were alive on discharge and received statin. Of these, 3189 (94%) were discharged with statin alone, 203 (6%) with a combination of a statin and bezafibrate. RESULTS: Thirty-day re-hospitalization rate was significantly lower in patients from the combination group than in their counterparts from the statin monotherapy group: 12.8% vs. 19%, p = 0.028. Multivariable analysis identified the combined bezafibrate/statin treatment as an independent predictor of reduced risk of 30-day re-hospitalization rate with odds ratio (OR) 0.53 (95% confidence interval [CI] 0.31-0.91), and it corresponded to 47% risk reduction. Other significant variables in our model associated with independent risk of 30-day re-hospitalization rate during the follow-up were female gender (OR 1.43, CI 1.05-1.95, p = 0.03) and age > 65 years (OR 1.49, CI 1.13-1.95, p = 0.004). CONCLUSIONS: Adding bezafibrate to statin in smokers was associated with a significantly reduced 30-day rate of re-hospitalization after ACS.

Comparison of statin alone versus bezafibrate and statin combination in patients with diabetes mellitus and acute coronary syndrome.

Acute coronary syndromes (ACS) in patients with diabetes mellitus (DM) are associated with a high risk for major adverse cardiovascular events (MACEs) despite statin treatment. The impact of combined bezafibrate and statin therapy in patients with DM and ACS has not been specifically investigated. The aim of this study was to evaluate the association of combined therapy with 30-day MACEs in patients with DM participating in the nationwide Acute Coronary Syndrome Israeli Surveys (ACSIS). The study population comprised 3,063 patients with DM from the ACSIS 2000, 2002, 2004, 2006, 2008, and 2010 enrollment waves who were alive at discharge and received statins. Of these, 225 (7.3%) received on discharge combined bezafibrate and statin therapy, and 2,838 (92.7%) were treated with statins alone. MACEs were defined as a composite measure of death, recurrent myocardial infarction, recurrent ischemia, stent thrombosis, ischemic stroke, and urgent revascularization. The development of 30-day MACEs was recorded in 8% patients receiving combination therapy and 14.2% of those receiving statins alone (p = 0.01). Crude 1-year mortality and 30-day rehospitalization rates were also significantly lower in patients receiving combination therapy: 4.0% versus 8.1% (p = 0.03) and 13.3% versus 21.6% (p = 0.003), respectively. Multivariate analysis identified combined therapy as an independent predictor of reduced risk for 30-day MACEs, with an odds ratio of 0.56 (95% confidence interval 0.34 to 0.92), corresponding to a 44% relative risk reduction. In conclusion, a significantly lower risk for 30-day MACEs was observed in statin-treated patients with DM who also received bezafibrate after ACS. Signals regarding improvement of 30-day rehospitalization and 1-year mortality rates emerged as well.

Coronary calcium in patients with and without diabetes: first manifestation of acute or chronic coronary events is characterized by different calcification patterns.

BACKGROUND: Coronary artery calcification (CAC) is closely related to coronary atherosclerosis. However, less is known about the clinical significance of extensive CAC (ECAC) in regard to types of first coronary events (acute vs. chronic). Diabetes mellitus (DM) represents a strong risk factor for CAD although its association with CAC is controversial. Aiming to elucidate these controversies we investigated the long-term outcome of coronary artery disease (CAD) in relation to degree of CAC in patients with and without DM from our annual cheek-up outpatient clinic. METHODS: Coronary artery computed tomography (CT) was performed in 667 patients who were yearly evaluated during a mean follow-up period of 6.3 ±3.4 year. The following 4 CAC categories were established: calcium absence; total calcium score (TCS): 1-100 AU; TCS: 101-600 AU and ECAC: TCS above 600 AU. Acute event was defined as first acute myocardial infarction (MI) or a new unstable angina. First chronic event was defined as a positive stress test with a consequent elective percutaneous coronary intervention or coronary artery bypass grafting. RESULTS: 628 subjects (94%) were free from any cardiac events, 39 (6%) experienced first cardiac event: 18 of them suffered acute and 21 chronic events. There were 67 patients with and 600 patients without DM: 78% of patients with DM presented CAC vs. 50% of patients without DM (p < 0.001).The mean TCS was 17 times higher in the chronic than in the acute events group: 914 vs. 55 AU, p < 0.001. In 95% of the patients with chronic events more than one calcified vessel was found, compared to 67% of the patients with acute events and only 30% of those without events (p < 0.001). Incidence of CAD events (all types pooled together) rose consequently from 2% in subjects without CAC to 34% in subjects with ECAC (p < 0.001). However, among the 32 subjects with ECAC, 11 (34%) developed chronic event while none of them had acute event. In contrast, none of subjects with TCS =0 or TCS 1-100 AU presented with chronic events. Subjects with TCS 101-600 AU presented 10 (9%) chronic and 5 (4.5%) acute events (p < 0.001). CONCLUSIONS: Asymptomatic subjects with ECAC are not firstly manifested as acute coronary events but presented a high level of chronic CAD-related events during the 6.3 ±3.4 year follow-up. In contrast, first acute CAD-related events occurred mostly in subjects with mild and moderate CAC score.

Progression of coronary artery calcification is associated with long-term cardiovascular events in hypertensive adults.

OBJECTIVES: Coronary artery calcification (CAC) is an independent predictor of cardiovascular (CV) events in hypertensive adults. However, the additive value of serial CAC measurements for risk stratification is unclear. The aim of the present study was to find whether CAC progression predicts long-term CV events in hypertensive patients. METHODS: The study group included 210 patients (mean age 64 ± 5.6 years, 54% men), a subgroup of 544 participants in the calcification side arm of the INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy). All were free of symptoms or known CV disease, had at least two CT scans 1 year apart, and had available long-term follow-up. Progression of CAC was defined as the absolute change in CAC score between maximal score during follow-up and baseline score. The endpoint was the first CV event after the last CT scan. Three categories of CAC progression were defined. Zero progression was defined as 'nonprogressors', and progression below and above the median of maximal progression were defined as 'slow progressors' and 'rapid progressors', respectively. RESULTS: During 15 years of follow-up (mean 11.4 ± 4.4), 83 patients experienced a first CV event. The rate of events was higher in rapid (29/59, 49%), and slow (36/78 46%) than in nonprogressors (18/73 25%); (P=0.005). Compared with nonprogressors, the adjusted hazard ratio for CV events was 1.91 [95% confidence interval (95% CI); 1.05-3.47] in the slow, and 2.13 (95% CI; 1.12-4.03) in the rapid progressors. CONCLUSION: In hypertensive patients, progression of CAC is associated with long-term CV events.

Second-hand tobacco smoke in never smokers is a significant risk factor for coronary artery calcification.

OBJECTIVES: The aim of this study was to assess the relationship of the extent of subclinical atherosclerosis measured by coronary artery calcification (CAC) to the extent of second-hand tobacco smoke (SHTS) exposure in asymptomatic people who never smoked. BACKGROUND: An association between SHTS and CAC was recently reported in a single study, but the quantitative aspects of the relationship are not known. METHODS: A cohort of 3,098 never smokers 40 to 80 years of age, enrolled in the FAMRI-IELCAP (Flight Attendant Medical Research Institute International Early Lung Cancer Action Program) screening program, completed a SHTS questionnaire, and had a low-dose nongated computed tomography scan. The questionnaire provided a quantitative score for total SHTS exposure, as well as separately as a child and as an adult at home and at work; 4 categories of exposure to SHTS were identified (minimal, low, moderate, and high exposure). CAC was graded using a previously validated ordinal scale score that ranged from 0 to 12. Logistic regression analysis of the prevalence and ordered logistic regression analysis of the extent of CAC were performed to assess the independent contribution of SHTS adjusted for age, sex, diabetes, hypercholesterolemia, hypertension, and renal disease. Linear and quadratic regression analyses of CAC and SHTS were performed. RESULTS: The prevalence of CAC was 24.3% (n = 754) and was significantly higher in those with more than minimal SHTS exposure compared with those with minimal SHTS exposure (26.4% vs. 18.5%, p < 0.0001). The adjusted odds ratios for CAC prevalence were 1.54 (95% confidence interval: 1.17 to 2.20) for low SHTS exposure, 1.60 (95% confidence interval: 1.21 to 2.10) for moderate exposure, and 1.93 (95% confidence interval: 1.49 to 2.51) for high exposure. The association of the extent of SHTS with the extent of CAC was confirmed by the adjusted odds ratio (p < 0.0001). CONCLUSIONS: The presence and extent of CAC were associated with extent of SHTS exposure even when adjusted for other risk factors for CAC, suggesting that SHTS exposure causes CAC.

Coronary artery calcification is associated with the development of hypertension.

BACKGROUND: Hypertension (HTN) is associated with coronary artery calcification (CAC). We hypothesized that preexisting CAC is associated with the development of HTN. METHODS: This study included 483 normotensive subjects (mean age 54 years, 83% males) who underwent a baseline evaluation of their CAC score with ungated dual-section computed tomography during 2001-2002 and returned for at least the first annual follow-up. All subjects underwent an annual examination and were followed for a mean period of 6.6 ± 3.2 years to identify newly developed HTN. Data on the patient's medical history, physical examination and laboratory evaluations were collected. RESULTS: During the follow-up, 104 subjects developed HTN. The rate of newly developed HTN was significantly higher among those with CAC (60 of 223 subjects; 27%) than among those without CAC (44 of 260; 17%) (P < 0.01). The presence of CAC predicted the development of HTN with a hazard ratio of 1.73 (95% confidence interval, 1.17-2.56; P < 0.01). After adjustment for age, sex, body mass index, smoking, baseline systolic blood pressure, and levels of glucose, triglycerides, and low-density lipoprotein cholesterol, the presence of CAC still predicted the development of HTN with a hazard ratio of 1.63 (95% confidence interval, 1.02-2.60; P = 0.04). CONCLUSIONS: Preexisting CAC is associated with the development of HTN.

Cardiovascular events in patients received combined fibrate/statin treatment versus statin monotherapy: Acute Coronary Syndrome Israeli Surveys data.

BACKGROUND: The effect of combination of fibrate with statin on major adverse cardiovascular events (MACE) following acute coronary syndrome (ACS) hospitalization is unclear. The main aim of this study was to investigate the 30-day rate of MACE in patients who participated in the nationwide ACS Israeli Surveys (ACSIS) and were treated on discharge with a fibrate (mainly bezafibrate) and statin combination vs. statin alone. METHODS: The study population comprised 8,982 patients from the ACSIS 2000, 2002, 2004, 2006, 2008 and 2010 enrollment waves who were alive on discharge and received statin. Of these, 8,545 (95%) received statin alone and 437 (5%) received fibrate/statin combination. MACE was defined as a composite measure of death, recurrent MI, recurrent ischemia, stent thrombosis, ischemic stroke and urgent revascularization. RESULTS: Patients from the combination group were younger (58.1±11.9 vs. 62.9±12.6 years). However, they had significantly more co-morbidities (hypertension, diabetes), current smokers and unfavorable cardio-metabolic profiles (with respect to glucose, total cholesterol, triglyceride and HDL-cholesterol). Development of MACE was recorded in 513 (6.0%) patients from the statin monotherapy group vs. 13 (3.2%) from the combination group, p = 0.01. 30-day re-hospitalization rate was significantly lower in the combination group: 68 (15.6%) vs. 1691 (19.8%) of patients, respectively; p = 0.03. Multivariable analysis identified the fibrate/statin combination as an independent predictor of reduced risk of MACE with odds ratio of 0.54, 95% confidence interval 0.32-0.94. CONCLUSION: A significantly lower risk of 30-day MACE rate was observed in patients receiving combined fibrate/statin treatment following ACS compared with statin monotherapy. However, caution should be exercised in interpreting these findings taking into consideration baseline differences between our observational study groups.