Francis Heart Study Research Articles

Epicardial fat modifies the relationship between coronary calcium score and all-cause mortality: The St. Francis Heart Study

ObjectiveEpicardial fat is associated with cardiovascular risk factors and adverse outcomes. However, it is not clear if epicardial fat remains to be a mortality risk when coronary calcium score (CAC) is taken into account. MethodsWe studied the 1005 participants from the St. Francis Heart Study who were apparently healthy with CAC scores at 80th percentile or higher for age and gender, randomly assigned to placebo or statin therapy. At baseline, lipid profiles and non-contrast CT images were obtained where the epicardial fat volume was analyzed. Likelihood ratio testing was used to assess the additional prognostic value of epicardial fat to CAC for the risk of all-cause mortality. ResultsIncreased epicardial fat volume was associated with higher CAC. For each unit increase in lnCAC, the average epicardial fat volume increased by 3.34 mL/m2. After a mean follow-up period of 17 years, 179 (18%) participants died. Increased epicardial fat volume was associated with an adjusted hazard ratio of 1.11 (95% CI: 1.02 to 1.20) predicting all-cause mortality. In the stratified analysis testing strata of epicardial fat and CAC, those with increased epicardial fat and increased CAC had the highest risk of death. Compared with a model containing lnCAC and traditional risk factors, a model additionally containing epicardial fat volume yielded a better model fit (likelihood ratio test p < 0.001). ConclusionIncreased epicardial fat volume is associated with increased all-cause mortality risk. In addition, it portends incremental prognostic value to CAC score in mortality prediction.

Favorable Change Of Epicardial Fat Features Is Associated With Improved Lipid Profile From Statin Therapy And Reduced Long Term All-Cause Mortality

Introduction: Low epicardial fat density and high epicardial fat volume are associated with adverse lipid profile. However, it is not clear if improving lipid profile from statin therapy is associated with favorable change of epicardial fat features. We explored this association in St. Francis Heart Study.

Long-term all-cause mortality among asymptomatic individuals with 80th percentile of coronary calcium score based on age and gender in the St. Francis Heart Study.

High coronary artery calcium score (CAC) is a significant risk factor for cardiovascular morbidity and mortality. We investigated the long-term outcome of subjects with elevated CAC. We studied 1005 participants of The St. Francis Heart Study who were asymptomatic and apparently healthy and had CAC scores at 80th percentile or higher for age and gender. They were randomized to receive atorvastatin 20 mg daily or placebo for up to 5 years. We used an as-treated study design accounting for cross-overs at the end of the original trial. All-cause mortality risk was assessed using adjusted hazard ratios. Mean age was 59 ± 6 years and 26% (N = 263) were female. After 17 ± 3 years follow-up 176 subjects died. High CAC at baseline was associated with increased mortality risk with adjusted hazard ratio for logarithmic transformed CAC at 1.33 and 95% confidence interval 1.06-1.68. The mortality risk associated with CAC was similar between the group with high-sensitivity CRP ≥2 and <2 mg/dL. Those with a family history of premature coronary artery disease exhibited a higher mortality risk in association with high CAC with an adjusted hazard ratio 1.51 (1.09, 2.09). Elevated CAC is an independent risk for long-term all-cause mortality. The screening of CAC score in addition to identifying conventional risk factors can differentiate asymptomatic individuals with and without increased long-term mortality risk.

Collective impact of conventional cardiovascular risk factors and coronary calcium score on clinical outcomes with or without statin therapy: The St Francis Heart Study

Background and aimsThe efficacy of statin therapy remains unknown in patients eligible for statin therapy with and without elevated coronary calcium score (CAC). The study sought to evaluate how cardiovascular risk factors, expressed in terms of statin eligibility for primary prevention, and CAC modify clinical outcomes with and without statin therapy. MethodsWe conducted a post-hoc analysis of the St. Francis Heart Study treatment trial, a double-blind, placebo-controlled randomized controlled trial of atorvastatin (20 mg), vitamin C (1 g), and vitamin E (1000 U) daily, versus placebos in 990 asymptomatic individuals with CAC ≥ 80th percentile for age and gender. Primary cardiovascular outcomes included non-fatal myocardial infarction or coronary death, coronary revascularization, stroke, and peripheral arterial revascularization. We further stratified the treatment and placebo groups by eligibility (eligible when statin indicated) for statin therapy based on 2013 ACC/AHA guidelines and based on CAC categories. ResultsAfter a median follow-up of 4.8 years, cardiovascular events had occurred in 3.9% of the statin treated but not eligible, 4.6% of the untreated and not eligible, 8.9% of the treated and eligible and 13.4% of the untreated and eligible groups, respectively (p<0.001). Low CAC (<100) occurred infrequently in statin eligible subjects (≤4%) and was associated with low 10-year event rate (<1 per 100 person-years). In contrast, high CAC (>300) occurred frequently in more than 35% of the statin not eligible subjects and was associated with a high 10-year event rate (≥17 per 100 person-years). Risk prediction improved significantly when both clinical risk profile and CAC score were combined (net reclassification index p = 0.002). ConclusionsUnder the current statin treatment guidelines a small number of statin eligible subjects with low CAC might not benefit from statin therapy within 5 years. However, the statin not eligible subjects with high CAC have high event rate attributing to loss of opportunity for effective primary prevention.

Coronary artery calcification score as tool for risk assessment among families with premature coronary artery disease

IntroductionThere is discussion about incorporating a family history (FamHis) of premature coronary artery disease (CAD) in risk score algorithms. However, FamHis provides information on individual risk. Coronary artery calcification score (CACS) is a metric of atherosclerosis that may determine the individual risk within families at high risk of premature CAD. MethodsIn asymptomatic individuals (n = 704), we assessed the association between FamHis of CAD and elevated CACS. To assess the predictive value of CACS in individuals with a FamHis of CAD, we performed a post-hoc analysis on the St. Francis Heart Study (n = 834). We assessed, in a case control design, the risk of future CAD in individuals with a FamHis of CAD and either CACS >80th percentile or no CACS at all. ResultsIndividuals with a FamHis for CAD had an increased risk for elevated CACS (adjusted odds ratio (OR) 2.23 (95% CI 1.48–3.36); p < 0.05), compared to those without a FamHis. In the prospective study (3.5 years follow-up), the event rate equally low in those with a positive FamHis and a negative FamHis (0% vs. 1%), if they had a CAC of 0. However, in those with CACS >80th percentile, a FamHis of CAD doubled the CAD event rate (positive FamHis 12.5% vs. negative FamHis 6.8%; adjusted HR 2.08 (95% CI 1.09–3.87; p < 0.05). ConclusionCAC scoring leads to risk discrimination among those with a positive FamHis for premature CAD. These results support testing CAC score in asymptomatic individuals with a positive FamHis to identify a high risk population.

Abstract 13148: Combined Association of Conventional Cardiovascular Risk Profile and Coronary Artery Calcium Score (CAC) With Cardiovascular Risk and CAC Progression: The St Francis Heart Study

Objective: Both coronary artery calcium (CAC) and clinical risk profile (RP) predict cardiovascular (CV) risk. Little is known about the association of combined CAC and RP with risk of CV outcomes and CAC progression. Methods: We followed 1,225 asymptomatic adults from the observational arm of the St Francis Heart Study for a median of 3.9 years. Participants were categorized into four groups based on CAC and RP (using 2013 AHA guidelines for statin eligibility): group 1 (N=336) CAC&lt;80 th percentile (for age and gender), statin not indicated; group 2 (N=350) CAC&lt;80 th percentile, statin indicated; group 3 (N=209) CAC≥80 th percentile, statin not indicated and group 4 (N=330) CAC≥80 th percentile, statin indicated. We compared the risk among groups for a composite CV outcome that included non-fatal MI, coronary death, coronary revascularization, stroke and peripheral arterial revascularization. We also examined the association of groups with CAC progression at four years from baseline. Results: Mean age was 59±6 years. Those eligible for statin were older (61±5 vs 55±5 years) and more likely to be male (82% vs.51%) than those not eligible. Median [IQR] CAC was higher in statin eligible than in noneligible subjects, 0 [0-7] vs. 9 [0-54] for groups 1 and 2 and 210 [115-404] vs. 482 [257-837] for groups 3 and 4. Adjusted hazard ratio (95% CI) for the composite CV outcome was 6.9 (0.8-58.9), 15.2 (1.9-119.3), and 37.8 (4.8-297.2) for groups 2, 3 and 4, respectively compared to group 1. There was a higher progression of CAC from baseline to year 4 among group 3 (median: 210 to 350) and group 4 (482 to 822) compared to group 1 (0 to 3) and group 2 (9 to 16), P&lt;0.001. Conclusion: While higher CAC is associated with greater CV outcome risk and CAC progression, statin therapy eligibility is associated with a higher CV outcome risk both among those with and without elevated CAC. Our findings suggest that RP remains important and should not be overlooked when CAC testing is used.

High dose and long-term statin therapy accelerate coronary artery calcification

BackgroundIn randomized clinical trials statins and placebo treated patients showed the same degree of coronary artery calcium (CAC) progression. We reanalyzed data from two clinical trials to further investigate the time and dose dependent effects of statins on CAC. Additionally, we investigated whether CAC progression was associated with incident cardiovascular events. Methods and resultsData were pooled from two clinical trials: St. Francis Heart Study (SFHS) (419 and 432 patients treated with placebo and 20mg atorvastatin daily, respectively) and EBEAT Study (164 and 179 patients respectively treated with 10mg and 80mg atorvastatin daily). CAC scores were assessed at baseline, 2years and 4–6years in SFHS; in EBEAT they were measured at baseline and 12months. After a short-term follow-up (12 to 24months) placebo and low dose atorvastatin showed a similar CAC increase, although 80mg/daily atorvastatin increased CAC an additional 12–14% over placebo (p<0.001). In the long-term, atorvastatin caused a greater progression of CAC compared to placebo (additional 1.1%, p=0.04). In SFHS 42 cardiovascular events occurred after the second CT scan. The baseline and progression of CAC were greater in patients with events. However, only baseline CAC and family history of premature cardiovascular disease but not CAC progression were independent predictors of events. ConclusionsDespite a greater CAC increase with high dose and long-term statin therapy, events did not occur more frequently in statin treated patients. This suggests that CAC growth under treatment with statins represents plaque repair rather than continuing plaque expansion.

Adrenal Cortisol Hyper-Responsiveness as a Possible Cause of Obesity, Insulin Resistance and Cardiovascular Risk

Introduction: Increased cortisol concentrations due to endogenous over-secretion or exogenous administration result in obesity, insulin resistance, and increased risk of cardiovascular disease (CVD). We wanted to assess whether non pathological adrenal hyper responsiveness to ACTH could reproduce these changes and thus explain how stress, via the pituitary-adrenal axis, can also cause such abnormalities. Methods: ACTH stimulation test was performed on 1072 non diabetic healthy participants in the St. Francis Heart Study and multiple blood tests, anthropometric measurements and coronary calcium scores were also obtained. Results: Post stimulation cortisol concentrations were correlated with obesity, insulin resistance, lipid abnormalities, Framingham scores (all p ≤ 0.01), but not with blood pressure and not with coronary calcium scores. In multivariate models, increased cortisol secretion was significantly predictive of abdominal fat even after controlling for insulin resistance, and of insulin resistance even after controlling for abdominal fat. Conclusions: Adrenal hyper responsiveness may explain some of the observation of the relationship between stress and the metabolic abnormalities which can lead to CVD. Increased cortisol secretion predicts insulin resistance and obesity , independently of each other.

Abstract 16701: Conventional Cardiovascular Risk Modifies Clinical Outcomes Among Subjects With Elevated Coronary Artery Calcium Score With and Without Statin Therapy: Post Hoc Analysis From the St Francis Heart Study

Objective: Coronary artery calcium score (CAC) predicts cardiovascular (CV) risk independent of conventional risk profile. However, it remains unclear how clinical risk profile modifies CV outcomes among subjects with elevated CAC with and without lipid lowering therapy. Methods: We conducted a post hoc analysis of the treatment trial of the St. Francis Heart Study_double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg, vitamin C 1 g, and vitamin E 1,000 U daily, versus matching placebos in 993 asymptomatic individuals with CAC at or above the 80th percentile for age and gender. Primary CV outcomes included non-fatal MI or coronary death, coronary revascularization, stroke, and peripheral arterial revascularization. Among the placebo and treatment groups, we further stratified by eligibility for statin therapy based on current AHA guidelines yielding 4 subgroups: treated not eligible (+Rx/-E), placebo not eligible (-Rx/-E), treated eligible (+Rx/+E) and placebo eligible (-Rx/+E). Results: Mean age was 59±6 years. Those eligible were older (61±5 vs. 56±5 years) and more likely to be males (85% vs. 56%) than those not eligible. Median [IQR] CAC was higher in the eligible than not eligible groups (overall, p&lt;0.0001), 199 [112-396] (+Rx/-E), 207 [114-416] (-Rx/-E), 490 [289-791] (+Rx/+E) and 484 [286-837] (-Rx/+E). After a median follow up of 4.8 years, 4.0%, 4.8%, 9.8% and 15.4% had a CV event in +Rx/-E, -Rx/-E, +Rx/+E and -Rx/+E, respectively. After adjusting for CV risk factors and CAC, hazard ratio (95% CI) was 1.1 (0.4-2.9), 3.3 (1.1-9.4) and 4.9 (1.7-14.0) for -Rx/-E, +Rx/+E and -Rx/+E, respectively compared to +Rx/-E. There was a significant interaction between CAC and eligibility for statin therapy for a CV outcome (p=0.05). Conclusion: Among subjects with elevated CAC, those eligible for statin therapy have higher CAC and overall greater risk for a CV outcome than those not eligible. While statin therapy lowers CV risk among those eligible, it does not significantly alter CV risk among those not eligible. There is a significant interaction between CAC and statin therapy eligibility for a CV outcome. Our findings suggest that clinical risk profile remains an important risk modifier for CV outcomes among those with elevated CAC.

Asymptomatic Individuals With a Positive Family History for Premature Coronary Artery Disease and Elevated Coronary Calcium Scores Benefit From Statin Treatment: A Post Hoc Analysis From the St. Francis Heart Study

The goal of this study was to evaluate whether individuals with a positive family history for premature coronary artery disease (CAD) and coronary calcium scoring (CCS) above the 80th percentile might benefit from preventive treatment. First-degree relatives of patients with premature CAD have an increased risk for cardiovascular disease (CVD), whereas events are poorly predicted in these individuals. Surrogate markers, such as CCS, might refine risk scoring. Nevertheless, the outcome of the St. Francis Heart trial, which investigated the effect of atorvastatin 20 mg/day in asymptomatic individuals with CCS above the 80th percentile, did not reach statistical significance. We performed a post hoc analysis on the database of the St. Francis trial to assess efficacy of treatment with atorvastatin 20 mg/day in those with CCS above the 80th percentile and presence (n = 543) or absence (n = 462) of a positive family history for premature CAD. All participants received aspirin 81 mg/day. Primary outcome included coronary death, myocardial infarction, coronary revascularization, stroke, and arterial surgery. A total of 1,005 individuals, with a mean age of 59.0 ± 5.9 years and a median absolute CCS of 370 Agatston units (interquartile range: 183 to 662) participated in the trial. After a follow-up of 4.3 (interquartile range: 3.5 to 4.5) years, 7.2% of the treated individuals with a positive family history had a cardiovascular event versus 12.5% of the placebo group (hazard ratio [HR]: 0.55; 95% confidence intervals [CI]: 0.31 to 0.97; p = 0.040). This is comparable with a number needed to treat of 18.9. In individuals without a family history, events were minimally reduced: 6.6% in the treated versus 6.8% in the placebo group (HR: 1.04; 95% CI: 0.51 to 2.13; p = 0.912). The combination of a positive family history and CCS above the 80th percentile identifies a subgroup within the primary prevention population that receives greater benefit from statin treatment than the population at large. These results have important implications for future guidelines concerning individuals with a positive family history for premature CAD.

Atorvastatin and Antioxidants for the Treatment of Nonalcoholic Fatty Liver Disease: The St Francis Heart Study Randomized Clinical Trial

Nonalcoholic fatty liver disease (NAFLD) is defined as the spectrum of benign fatty liver to necroinflammation and fibrosis. Its prevalence has been found to be as high as 39%. It is estimated that up to 15% of those affected will go on to have progressive liver disease. Currently, there is no proven therapy for NAFLD. In this study, we aim to determine whether statin therapy may be an effective treatment for NAFLD and identify independent predictors of NAFLD. In all, 1,005 men and women, aged 50-70 years were randomized to receive either a daily combination of atorvastatin 20 mg, vitamin C 1 g, and vitamin E 1,000 IU vs. matching placebo, as part of the St Francis Heart Study randomized clinical trial. Liver to spleen (LS) ratios were calculated on 455 subjects with available computed tomography scans performed at baseline and follow-up to determine NAFLD prevalence. Baseline and final LS ratios were compared within treatment groups, and results were compared between the treatment and placebo groups using univariate and multivariate analyses. Mean duration of follow-up was 3.6 years. There were 80 patients with NAFLD at baseline. We identified baseline triglyceride levels (odds ratio (OR)=1.003, P<0.001) and body mass index (OR=0.10, P<0.001) as independent correlates of NAFLD. Treatment with atorvastatin combined with vitamins E and C significantly reduced the odds of NAFLD at the end of follow-up, 70 vs. 34% (OR=0.29, P<0.001). In conclusion, atorvastatin 20 mg combined with vitamins C and E is effective in reducing the odds of having hepatic steatosis by 71% in healthy individuals with NAFLD at baseline after 4 years of active therapy.

S1853 Atorvastatin for the Treatment of Nonalcoholic Fatty Liver Disease: the ST. Francis Heart Study Randomized Clinical Trial

Apoptosis and oxidative injury are recognized as the most important causes of hepatocyte injury in non-alcoholic fatty liver disease (NAFLD). We aimed to search for the association between serum alanine aminotransferase (ALT) levels and hepatocyte apoptosis and oxidative stress parameters in NAFLD. Fifty patients (24 male / 26 female, mean age: 47.3 ± 10.1 years) with biopsy-proven NAFLD were studied. While ALT was in normal range in 24 subjects, it was elevated in 26. Upper range of normal was set to 19 U/L for women and 30 U/L for men. While non-alcoholic fatty liver (NAFL) denotes simple steatosis, nonalcoholic steatohepatitis (NASH) denotes the presence of inflammation, ballooned hepatocytes and fibrosis. Liver oxidative stress was estimated on the basis of tissue gluthathione concentration, and superoxide dismutase (SOD), and malondialdehyde (MDA) activities in tissue and serum specimens. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor kB (NF-kB), antiapoptotic Bcl-2 protein, and tumor necrosis factor receptor (TNF-sRp55). The mean caspase 3 and 8 activity scores, oxidative stress parameters, mean necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Only patients with NASH had significantly higher caspase 3 and 8 activity, and serum MDA levels than those with NAFL (54.81±18.06, 39.81±27.43, p=0.04; 49.62±17.66, 26.17±15.03, p=0.03, and 5.09±0.77, 3.58±0.50, p= 0.049, respectively). Multiple regression analysis revealed that ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis (OR:0.99, p=0.74, CI: 0.991.00, and OR:0.99, p=0.71, CI:0.98-1.00, respectively). Area under the receiver operating characteristic curve (AUROC) did not show any significant sensitivity and specificity for discriminative power of ALT (according to the upper limits above) for the necroinflammatory and fibrosis severity (AUROC 0.49; 95 % CI: 0.57-0.91, and AUROC 0.43; 95 % CI: 0.190.67, and respectively). In conclusion, we demonstrated that apoptosis and oxidative stress are the main events contributing to disease progression in NAFLD and serum ALT values do not correlate well with the parameters of these injurious processes or the severity of resultant histological changes.

How Low-Risk Is a Coronary Calcium Score of Zero?

Coronary artery calcium (CAC) scoring by computed tomography (CT) has been the subject of intense interest and critical scrutiny since it was first reported as a clinical tool in 1990.1 With improvements in study design, greater availability of coronary CT scanners, and increased attention to the posttest prognosis of patient samples and asymptomatic individuals who have undergone coronary CT, CAC measurement is now considered a potentially useful test for improving coronary risk assessment in selected intermediate-risk asymptomatic patients in whom high CAC scores signify increased cardiovascular risk beyond that predicted by conventional cardiovascular risk factors alone.2 Article p 1693 At the other end of the spectrum, does a very low CAC score signify very low risk? An American Heart Association writing group3 stated that a CAC score of zero (CAC=0; ie, no calcified plaque detected) indicated 1) that the presence of atherosclerotic plaque, including unstable or vulnerable plaque, was highly unlikely; 2) that the presence of significant luminal obstructive disease was highly unlikely (negative predictive value on the order of 95% to 99%); and 3) that the risk of a cardiovascular event in the next 2 to 5 years was quite low (0.1 per 100 person-years). In addition, at least 1 early study suggested that CAC=0 might be useful in the emergency room setting as a tool to rule out myocardial ischemia in symptomatic patients.4 A recent review article5 suggested the same conclusions. However, as pointed out by a different …

Can coronary calcification measured by CT predict future coronary events?

Arad Y, Goodman KJ, Roth M, Newstein D, Guerci AD. Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol 2005;46:158-65. Background: The degree of coronary artery calcification

Treatment of Asymptomatic Adults With Elevated Coronary Calcium Scores With Atorvastatin, Vitamin C, and Vitamin E: The St. Francis Heart Study Randomized Clinical Trial

Treatment of Asymptomatic Adults With Elevated Coronary Calcium Scores With Atorvastatin, Vitamin C, and Vitamin E: The St. Francis Heart Study Randomized Clinical Trial

Treatment of Asymptomatic Adults With Elevated Coronary Calcium Scores With Atorvastatin, Vitamin C, and Vitamin E: The St. Francis Heart Study Randomized Clinical Trial

We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease (ASCVD) events. The electron beam computed tomography-derived coronary calcium score predicts coronary disease events. Small, uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events, but controlled, scientific demonstration of these effects is lacking. We conducted a double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg daily, vitamin C 1 g daily, and vitamin E (alpha-tocopherol) 1,000 U daily, versus matching placebos in 1,005 asymptomatic, apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender. All study participants also received aspirin 81 mg daily. Mean duration of treatment was 4.3 years. Treatment reduced total cholesterol by 26.5% to 30.4% (p < 0.0001), low-density lipoprotein cholesterol by 39.1% to 43.4% (p < 0.0001), and triglycerides by 11.2% to 17.0% (p < or = 0.02) but had no effect (p = 0.80) on progression of coronary calcium score (Agatston method). Treatment also failed to significantly reduce the primary end point, a composite of all ASCVD events (6.9% vs. 9.9%, p = 0.08). Event rates were related to baseline calcium score (pre-specified analysis) and may have been reduced in a subgroup of participants with baseline calcium score >400 (8.7% vs. 15.0%, p = 0.046 [not a pre-specified analysis]). Treatment with alpha-tocopherol, vitamin C, and low doses of atorvastatin (20 mg once daily) did not affect the progression of coronary calcification. Treatment may have reduced ASCVD events, especially in subjects with calcium scores >400, but these effects did not achieve conventional levels of statistical significance.

Rationale and Design of the St. Francis Heart Study: A Randomized Clinical Trial of Atorvastatin Plus Antioxidants in Asymptomatic Persons with Elevated Coronary Calcification

Early detection of asymptomatic subjects who are at risk for future cardiovascular events may allow for earlier medical treatment in order to prevent disease progression and future events. Electron-beam computed tomography accurately identifies people with increased coronary calcification, which is correlated with increased coronary plaque mass, increased likelihood of obstructive coronary disease, and increased likelihood of future cardiovascular events. The St. Francis Heart Study is a single-center combination study of men and women 50–70 years old that includes a natural history study of the relation between calcium scores and cardiovascular events ( n = 5582), the association of calcium scores with traditional and nontraditional coronary disease risk factors ( n = 1160), and a randomized clinical trial designed to assess the benefit of combination treatment with atorvastatin, vitamin C, and vitamin E, as compared to placebos, in subjects with elevated age- and gender-adjusted coronary calcification ( n = 1007). Mean follow-up duration will be 4 years. The study is proceeding on schedule with anticipated completion by August 2002. It should provide important information regarding the benefits of treating asymptomatic men and women who have elevated coronary artery calcium, using cholesterol reduction and antioxidant therapy. The article describes the design of the St. Francis Heart Study. Control Clin Trials 2001;22:553–572

SAI-3: Rationale and design of the St. Francis Heart Study: a randomized clinical trial of atorvastatin plus antioxidants in asymptomatic persons with elevated coronary calcium

SAI-3: Rationale and design of the St. Francis Heart Study: a randomized clinical trial of atorvastatin plus antioxidants in asymptomatic persons with elevated coronary calcium

Rationale and design of the St. Francis heart study: a randomized clinical trial of atorvastatin plus a antioxidants in asymptomatic persons with elevated coronary calcium

We prospectively examined the association between three adiposity indices, including body mass index (BMI), waist circumference (WC), and percentage of body fat (PBF), and risk of hypertension in normal-weight Chinese children.The current study included 1526 (713 boys and 813 girls) normal-weight Chinese children (age 6–14 years old), who were free of hypertension at baseline (2014). Heights, body weight, WC, and PBF (estimated by bioelectrical impedance analysis) were measured at the baseline. Blood pressure was repeatedly measured in 2014, 2015 and 2016. Hypertension was defined as either high systolic blood pressure and/or high diastolic blood pressure, according to age- and sex-specific 95th percentile for Chinese children. We used Cox proportional hazards model to calculate the association between exposures and hypertension. We identified 88 incident hypertension cases during two years of follow up. High BMI was associated with high risk of developing hypertension after adjusting for potential confounders. The adjusted hazard ratio for hypertension was 2.88 (95% CI: 1.24, 6.69) comparing two extreme BMI quartiles. Each SD increase of BMI (≈1.85 kg/m2) was associated with a 32% higher likelihood to developing hypertension (Hazard ratio = 1.32; 95% CI: 1.003, 1.73). In contrast, we did not find significant associations between WC or PBF and higher hypertension risk (p-trend >0.2 for both).High BMI, but not WC and PBF, was associated with high risk of hypertension in normal-weight Chinese children.