Burden Of Traditional Risk Factors Research Articles

Risk factor burden in familial hypercholesterolaemia with early onset coronary artery disease

Abstract Background Familial hypercholesterolaemia (FH) is considered a causal risk factor for premature coronary artery disease (CAD) with a priority placed on identifying index cases and their relatives for preventative interventions. However recent population sequencing studies have identified that not all FH mutation carriers develop CAD. We hypothesised that a significant burden of traditional risk factors is required in addition to genetic risk to develop CAD. Methods We interrogated the clinical registry of patients attending the CVD risk and Lipids clinic at St Bartholomew’s Hospital in London which serves a large multi-ethnic population. Patients were prioritized for genetic testing based on Simon Broome and Dutch Lipid criteria. A second cohort of patients from the clinic consisted of premature CAD patients without phenotypic FH. CAD was defined as > 50% stenosis in an epicardial vessel by invasive or non-invasive imaging. Results We identified 40 patients with genetically confirmed FH and CAD (FH+/CAD+) and 116 people with FH and without CAD (FH+/CAD-). Of 10 traditional risk factors evaluated, prevalence of each was higher in FH +/CAD+ compared to FH+/CAD- patients. Collectively, FH+/ CAD+ patients had a median number of risk factors of 5(4,6) compared to 4(3,5) for FH+/CAD- patients, (P<0.001). In non-FH patients, risk factors burden was higher in those with CAD (FH-/CAD+), compared to those without CAD: 5(4,6) V. 4(3,5) risk factors, respectively(P<0.001). Importantly, in patients who developed CAD, the traditional risk factor burden was greater in FH- patients than that of FH+ patients whereas, the genetic risk burden was greater in FH+ patients (Figure-1). The mean age of onset of CAD in both FH+ and FH- patients was comparable: 43± 10 V. 43± 12years. Patients with FH+/CAD+ were older (53± 11 V 49± 13 years, P=0.276) but had an earlier onset of CAD, when risk burden was greater (43± 8 years if ≥ 5 risk factors v 49± 15 years if < 5 risk factors, P=0.192). Conclusion In a selected population from a large specialist lipid clinic, we demonstrate that traditional risk factor burden is additive to genetic risk for the development and age of onset of CAD, supporting a disease liability threshold model in FH.Figure-1.Risk Burden in FH with CAD

Ischemic burden and cardiovascular mortality in 12 middle- and high-income European countries

Abstract Background Death rates from ischemic heart disease (IHD) are consistently higher in middle-income countries (MICs) than in high-income countries (HICs) in Europe, but the reasons are unknown. Purpose The main goal of this study was to disentangle the relation between patient-specific revascularization through percutaneous coronary intervention (PCI) and risk factor burden among European women and men from HICs and MICs Methods We enrolled 22,087 patients with myocardial infarction (MI) from 40 urban hospitals in 12 European countries (6 high-income and 6 middle-income countries; HICs and MICs, respectively) and quantified their traditional risk-factor burden (hypercholesterolemia, diabetes, current smoking and hypertension), the severity of their clinical presentation (incidence of ST-segment elevation MI [STEMI]) and their 30-day cardiovascular outcomes. We calculated women to men risk ratios (RRs) using inverse probability weighting models with estimates compared by interaction test on the log scale. Results Women and men from MICs were significantly (P<0.001) younger than those from HICs. Rates of hypertension and diabetes were significantly (P<0.001) higher in MICs compared to HICs for both women and men. By contrast, we did not find significant differences between country income levels, sex and rates of hypercholesterolemia. In line with these data the use of preventive medications was significantly (P<0.001) more common in MICs than in HICs and in women compared with men. Despite this, the rates of STEMI on hospital presentation were remarkably (P<0.001) higher in MICs than in HICs. (68.8% vs 57.7% in women and 71.0% vs 57.9% in men), and accordingly the case fatality rates for MI were consistently (P<0.001) higher in MICs than in HICs, with women having higher rates of mortality than men (10.3% vs 5.7%; RR: 1.90; 95% CI: 1.67-2.17 and 5.5%, vs 4.2%; RR: 1.31; 95% CI: 1.06-1.63; respectively; P interaction=0.002). Contrary to what was expected, MIC hospitals had higher rates of revascularization procedures than HIC hospitals both in women (72% vs 56%) and men (80% vs 61%). Although the rates of death were consistently lower in the population undergoing revascularization, still mortality remained significantly (P<0.001) higher in MICs than in HICs and in women than in men (6.9% vs 3.8% and 4.3% vs 2.3%; 10.3% vs 5.7%), but the relative RRs for the two country income groups did not significantly differ each other (P interaction=0.40). Conclusions Although the rates of revascularization procedures in MI were higher in MICs, the rates of death were substantially higher in MICs than in HICs. The high burden of risk factors in MICs appears to be the reason of a substantial increased baseline ischemic risk with higher rate of STEMI as MI clinical presentation. Better control of risk factors may mitigate the observed gap in mortality from MI between MICs and HICs, especially in women.

Abstract 13721: Coronary Artery Calcium for Risk Stratification Among Persons With Very-High High-Density Lipoprotein Cholesterol

Introduction: Persons with very-high high-density lipoprotein-cholesterol (HDL-C) may experience an increased mortality risk. However, the predictors of mortality among those with very-high HDL-C remain unknown. Hypothesis: Compared to traditional risk factors, coronary artery calcium (CAC) will more strongly stratify risk among individuals with very-high HDL-C. Aims: Among individuals with very-high HDL-C, to 1) calculate crude all-cause mortality rates across the burden of traditional risk factors and CAC, and 2) identify independent risk factors associated with all-cause mortality. Methods: There were 335 primary prevention patients from the CAC Consortium who had very-high HDL-C ( > 80 mg/dL in men, > 100 mg/dL in women) and available information on traditional CVD risk factors. Crude all-cause mortality rates were calculated per 1,000 person-years. Multivariable Cox proportional hazards regression assessed the association of traditional risk factors and CAC with mortality. Results: The mean age was 58.6 years old, 51.0% were women, 51.3% had prevalent CAC, and the median HDL-C was 100 mg/dL. There were 20 deaths (6.0%) over a median follow-up of 10.5 years, 7 (2.1%) of which were attributable to CVD. There was a stepwise higher crude mortality rate per 1,000 person-years across increasing CAC burden ( Central Illustration ). Independent of traditional risk factors, each 100 Agatston Unit increase in CAC score was associated with a 7% higher hazard of all-cause mortality (HR: 1.07, 95% CI: 1.01-1.12) and individuals with CAC > 1000 experienced a 5.75-fold higher hazard of mortality when compared to CAC=0 (HR: 5.75, 95% CI: 1.26-26.24). Beyond age, no traditional risk factor was associated with mortality in multivariable analyses. Conclusion: Measurement of CAC on non-contrast cardiac computed tomography may facilitate risk assessment among individuals with very-high HDL-C.

PO-01-196 MINORITIES HAVE GREATER LONG-TERM ATRIAL FIBRILLATION-FREE SURVIVAL POST ABLATION DESPITE LOWER REFERRAL RATES AND HIGHER INCIDENCE OF BASELINE COMORBIDITIES

Significant differences in the incidence and management of atrial fibrillation (AF) have been observed based on patient sex and race. Women with AF tend to be older, have higher stroke/mortality risk, and receive catheter ablation less often than men, while racial minority patients paradoxically have lower prevalence of AF than nonminority patients despite a higher burden of traditional risk factors. To explore the sex and racial profile of patients undergoing catheter ablation for AF and their ablation outcomes. We conducted a retrospective cross-sectional analysis of all de novo AF catheter ablations performed from Jan 6, 2015 to Oct 28, 2021 using the common electronic health record across a large healthcare system. Inclusion criteria included a self-identification race and having at least one follow-up visit after the blanking period. Patients who self-identified as Caucasian American/White race were defined as Nonminority while patients who self-identified as Black or African American, American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander and multiracial were defined as Racial minority. A survival analysis of the first documented recurrence of any atrial tachyarrhythmia was also performed. A total of 1,634 subjects with a median age of 68 (IQR=61-75) years were analyzed. Patients were predominantly male (65.9%) and nonminority (79.6%) with mostly paroxysmal AF (60.9%). Among minority patients, 35.9% were identified as Black/African Americans, 18.3% as Asians, and 44.0% as multiracial. Minority patients were more likely to be younger (p<0.001) and have diabetes mellitus (p<0.001), heart failure (p<0.001), chronic kidney disease (p<0.001), prior stroke/transient ischemia attack (p=0.012) and hypertension (p<0.001) while less likely to have obstructive sleep apnea (p=0.01), cancer (p=0.036) and persistent AF (p=0.05). Minority patients had lower odds of AF recurrences (hazard ration (HR) = 0.73, 95% CI 0.58 – 0.95; Figure 1a) which remained significant after adjusting for baseline differences (adjusted HR = 0.70, 95% CI 0.55 – 0.91, p<0.001) while sex had no effect on AF recurrences (Figure 1). Referral for catheter ablation for AF favored nonminority and male patients. Despite higher incidence of comorbidities and lower referral rates, minority patients had lower adjusted odds of AF recurrences. Further exploration is warranted to understand the factors underlying these utilization and outcomes disparities.

Socioeconomic determinants of health, traditional risk factors and cardiovascular outcomes in Australia

BackgroundCardiovascular disease burden is decreasing, but these reductions have not been distributed equally amongst socioeconomic groups. ObjectivesThe aim of this study was to define the relationships between different domains of socioeconomic health, traditional cardiovascular risk factors and cardiovascular events. MethodsThis was a cross-sectional study of local government areas (LGAs) in Victoria, Australia. We used data from a population health survey combined with cardiovascular event data derived from hospital and government data. Four socioeconomic domains: educational attainment, financial wellbeing, remoteness, and psychosocial health, were generated from 22 variables. The primary outcome was a composite of non-STEMI, STEMI, heart failure and cardiovascular deaths per 10,000 persons. Linear regression and cluster analysis were used to assess the relationships between risk factors and events. ResultsAcross 79 LGAs there were 33,654 interviews conducted. All socioeconomic domains were associated with burden of traditional risk factors, including hypertension, smoking, poor diet, diabetes, and obesity. Financial wellbeing, educational attainment and remoteness were all correlated with cardiovascular events on univariate analysis. After multivariate adjustment for age and sex, financial wellbeing, psychosocial wellbeing, and remoteness were associated with cardiovascular events, while educational attainment was not. After including traditional risk factors only financial wellbeing and remoteness remained correlated with cardiovascular events. ConclusionsFinancial wellbeing and remoteness independently be associated with cardiovascular events, while educational attainment and psychosocial wellbeing are attenuated by traditional cardiovascular risk factors. Poor socioeconomic health is clustered in certain areas, which have high cardiovascular event rates.

Impact of smoking on outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

Smoking is a well‑established risk factor for cardiovascular diseases. However, in patients with ST‑segment elevation myocardial infarction (STEMI), smoking has been associated with better clinical outcomes; this phenomenon became known as the "smoker's paradox." The aim of this study was to evaluate the association between smoking and clinical outcomes in STEMI patients treated with primary percutaneous coronary intervention (PCI), using 3 large national registries. We retrospectively analyzed the data of 82 235 hospitalized STEMI patients treated with primary PCI. Among the analyzed population, 30 966 patients (37.96%) were smokers, and 51 269 (62.36%) were nonsmokers. We evaluated the baseline characteristics, pharmacotherapy, clinical outcomes, and readmission causes in a 36‑month follow‑up. The smokers were significantly younger (median [interquartile range] age, 58 [52-64] vs 68 [59-77] years; P <0.001) than the nonsmokers, and there were more men in this group. The patients who smoked were less likely to have traditional risk factors, as compared with the nonsmokers. In the unadjusted analysis, in‑hospital and 36‑month mortality and rehospitalization rates were lower in the smokers group. However, after adjustment for baseline characteristics that differed between the 2 groups, the multivariable analysis showed that tobacco use was one of the independent risk factors for 36‑month mortality (hazard ratio, 1.11; 95% CI, 1.06-1.18; P <0.001). In the present large‑scale, registry‑based analysis, the observed lower 36‑month crude rates of adverse events among the smokers, as compared with the nonsmokers, might be partially explained by a significantly lower burden of traditional risk factors and younger age of the smokers. After accounting for age and other baseline differences, smoking was found to be one of the independent risk factors for 36‑month mortality.

Early Contributors to Healthy Arterial Aging Versus Premature Atherosclerosis in Young Adults: The Bogalusa Heart Study.

BackgroundEarly identification of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease risk stratification and prevention. We sought to identify predictors for the long‐term absence of carotid plaque among young adults.Methods and ResultsWe included 508 participants from the Bogalusa Heart Study without clinical atherosclerotic cardiovascular disease who were free of carotid plaque at baseline (2001–2002) and underwent ultrasound imaging at follow‐up (2013–2016). Modified Poisson regression estimated the persistent absence of plaque over 12.8 years. Participants were on average age 36.2 years at baseline, 64% were women, and 29% were Black. Although nearly all participants (97%) had a 10‐year atherosclerotic cardiovascular disease risk <7.5%, there were 162 people (32%) who developed premature atherosclerosis. Aside from younger age (risk ratio [RR], 1.21; 95% CI, 1.07–1.36, per 10 years) and a total cholesterol/high‐density lipoprotein cholesterol ratio <3.5 (RR, 1.15; 95% CI, 1.01–1.30), normal values of traditional risk factors did not predict long‐term absence of plaque. Independent from traditional markers including glomerular filtration rate, serum calcium‐phosphate product (RR, 1.07; 95% CI, 1.01–1.14, per 1‐SD lower), phosphate (RR, 1.15; 95% CI, 1.03–1.29, per 1 mg/dL lower), and dietary sodium <2300 mg/day (RR, 1.20; 95% CI, 1.02–1.41) were significantly associated with the non‐development of plaque.ConclusionsNearly one third of young adults with a low burden of traditional risk factors developed premature atherosclerosis. Beyond younger age and an ideal lipoprotein profile, lower calcium‐phosphate homeostasis and low sodium intake were associated with long‐term absence of carotid plaque. These results suggest that dietary and intrinsic minerals are early contributors to the development of arterial aging phenotypes.

Abstract P175: Predicting Healthy Arterial Aging Versus Premature Atherosclerosis In Young Adults: The Bogalusa Heart Study

Introduction: Early differentiation of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease (ASCVD) risk stratification and prevention. We sought to identify predictors for the long-term absence of carotid plaque in young adults. Hypothesis: Calcium and phosphate are found in excess in atherosclerotic lesions, therefore we hypothesized that mineral markers may help to explain residual heterogeneity in arterial aging phenotypes beyond traditional ASCVD risk factors. Methods: We included 508 participants from the Bogalusa Heart Study without clinical ASCVD who were free of carotid plaque at baseline (2001-02) and underwent ultrasound at follow-up (2013-16). Modified Poisson regression estimated the persistent absence of carotid plaque over 12.8 years. Results: Participants were on average 36.2 years old at baseline, 64% were women, and 29% were African American. Although a majority (97%) of participants had a 10-year ASCVD risk &lt;7.5%, only 68% remained free of plaque ( Figure ). Beyond younger age (RR=1.20, 95% CI: 1.07-1.36, per 10 years) and a total cholesterol-HDL-cholesterol ratio &lt;3.5 (RR=1.15, 95% CI: 1.01-1.30), normal values of traditional risk factors did not predict long-term absence of plaque. Independent from traditional markers, including glomerular filtration rate, serum calcium-phosphate product (RR=1.08, 95% CI: 1.01-1.14, per 1-SD lower), phosphate (RR=1.15, 95% CI: 1.03-1.29, per 1 mg/dL lower), and dietary sodium &lt;2300 mg/day (RR=1.20, 95% CI: 1.03-1.41) significantly associated with non-development of plaque. Conclusions: Lower calcium-phosphate homeostasis and low sodium intake independently associated with long-term absence of carotid plaque. However, nearly one-third of young adults with a relatively low burden of traditional risk factors developed premature atherosclerosis. These results suggest that dietary and intrinsic minerals are early contributors to the development of arterial aging phenotypes.

Lifetime risk of cardiometabolic mortality according to vitamin D status of middle and older-aged adults: NHANES III mortality follow-up

The predictive value of total 25-hydroxyvitamin D (25(OH)D, a biomarker of vitamin D status) in relation to lifetime risk of cardiometabolic mortality is not known. The purpose of this study was to determine the association between standardized and annualized total 25(OH)D levels and lifetime risk for cardiometabolic mortality in middle- to older-aged adults. In this study, we followed up 7958 participants in the Third National Health and Nutrition Examination Survey from 1988 to 1994 (NHANES III) until the occurrence of cardiometabolic death or attainment of 95 years of age (median follow-up 17.9 years, 1371 cardiometabolic-deaths). Lifetime risks were estimated according to recommended total 25(OH)D cutoffs by national guidelines, and a combination of total 25(OH)D status and traditional risk factor burden. We also explored variation in lifetime risk estimates by levels of body mass index (BMI). The results of this study showed that annualized total 25(OH)D <30 nmol/L was associated with high lifetime risk of cardiometabolic mortality (40%). Lifetime risks of cardiometabolic mortality were similar for annualized levels between 30–< 50 nmol/L, 50–< 75 nmol/L and ≥75 nmol/L (31–33%). Lifetime risk was highest among participants with annualized total 25(OH)D <30 nmol/L and ≥2 major traditional risk factors (45%), whereas lifetime risk was lowest among participants with annualized 25(OH)D ≥30 nmol/L and low-intermediate risk factors (28%). Lifetime risk estimates were similar across BMI categories. In conclusion, a single measurement of vitamin D deficiency (annualized levels <30 nmol/L) in middle- to older-aged adults is a strong predictor of high lifetime risk for cardiometabolic mortality, particularly among those with high burden of traditional risk factors.

Coronary calcium score improves the estimation for pretest probability of obstructive coronary artery disease and avoids unnecessary testing in individuals at low extreme of traditional risk factor burden: validation and comparison of CONFIRM score and genders extended model

BackgroundReliability of models for estimating pretest probability (PTP) of obstructive coronary artery disease (CAD) has not been investigated in individuals at low extreme of traditional risk factor (RF) burden. Thus, we sought to validate and compare CONFIRM score and Genders extended model (GEM) among these individuals.MethodsWe identified symptomatic individuals with 0 or 1 RF who underwent coronary calcium scan and coronary computed tomographic angiography (CCTA). Follow-up clinical data were also recorded. PTP of obstructive CAD for every individual was estimated according to CONFIRM score and GEM, respectively. Area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI) and Hosmer–Lemeshow (H-L) test were used to assess the performance of models.ResultsThere were 1201 individuals with 0 RF and 2415 with 1 RF. The AUC for GEM was significantly larger than that for CONFIRM score, no matter in individuals with 0 (0.843 v.s. 0.762, p < 0.0001) or 1 (0.823 v.s. 0.752, p < 0.0001) RF. Compared to CONFIRM score, GEM demonstrated positive IDI (5% in individuals with 0 RF and 8% in individuals with 1 RF), positive NRI (41.50% in individuals with 0 RF and 40.19% in individuals with 1 RF), better prediction of clinical events and less discrepancy between observed and predicted probabilities, resulting in a significant decrease of unnecessary testing, especially in negative individuals.ConclusionIn individuals at low extreme of traditional RF burden of CAD, the addition of coronary calcium score provided a more accurate estimation for PTP and application of GEM instead of CONFIRM score could avoid unnecessary testing.

Clinical Features and Gaps in the Management of Probable Familial Hypercholesterolemia and Cardiovascular Disease.

Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease (ASCVD). The introduction of potent therapeutic agents underlies the importance of improving clinical diagnosis and treatment gaps in FH.Methods and Results:A regional database of 1,690 adult patients with high-probability FH based on age-dependent peak-low-density lipoprotein cholesterol (LDL-C) cut-offs and exclusion of secondary causes of severe hypercholesterolemia, was examined to explore the clinical manifestations and current needs in the management of ASCVD, which was present in 248 patients (15%), of whom 83% had coronary artery disease (CAD); 19%, stroke; and 13%, peripheral artery disease. ASCVD was associated with male gender, higher peak LDL-C, lower high-density lipoprotein cholesterol (HDL-C), and traditional risk factor burden. Despite high-intensity statin (prescribed in 83% and combined with ezetimibe in 42%), attainment of LDL-C treatment goals was low, and associated with treatment intensity and drug adherence. Multivessel CAD (adjusted hazard ratios (HR), 3.05; 95% CI: 1.65-5.64), myocardial infarction, and the presence of ≥1 traditional risk factor (HR, 2.59; 95% CI: 1.42-4.71), were associated with repeat coronary revascularizations, in contrast with peak LDL-C >300 mg/dL (HR, 1.13; 95% CI: 0.66-1.91). Main manifestations of ASCVD in FH patients were premature, multivessel CAD with need for recurrent revascularization, associated with classical cardiovascular risk factors but not with peak LDL-C. In spite of intensive therapy with lipid-lowering agents, treatment gaps were significant, with low attainment of LDL-C treatment goals.

Cardiorespiratory fitness, muscle strength and risk of cardiovascular outcomes

Physical fitness is associated with lower cardiovascular disease (CVD) mortality, with multiple studies demonstrating a consistent, inverse association between cardiorespiratory fitness (CRF) and mortality even after adjustment for the traditional risk factor burden (1,2). This association has persisted across the lifespan, as a single measurement of CRF in midlife is strongly associated with the lifetime risk for cardiovascular mortality decades later. Cardiorespiratory fitness is associated with a reduced risk of several adverse health outcomes (3-9). Although CRF is recognized as an important marker of both functional ability and cardiovascular health, it is currently one of the most important risk factors that is not routinely and regularly assessed in either the general or specialized clinical setting. The relationship between CRF and other nonfatal cardiovascular outcomes is not well understood, which reflects the limited data on nonfatal cardiovascular events including atrial fibrillation, heart failure (HF) and stroke with objectively measured physical fitness and muscle strength. Much of the focus on the mechanisms of benefit of physical exercise and CRF have focused on prevention of atherosclerosis and its complications, although the specific effects of physical exercise on cardiac and vascular function suggest that low CRF might be an important risk factor for HF and other nonfatal cardiovascular events (10).

Determinants of Racial/Ethnic Differences in Cardiorespiratory Fitness (from the Dallas Heart Study)

Previous studies have demonstrated ethnic/racial differences in cardiorespiratory fitness (CRF). However, the relative contributions of body mass index (BMI), lifestyle behaviors, socioeconomic status (SES), cardiovascular (CV) risk factors, and cardiac function to these differences in CRF are unclear. In this study, we included 2,617 Dallas Heart Study participants (58.6% women, 48.6% black; 15.7% Hispanic) without CV disease who underwent estimation of CRF using a submaximal exercise test. We constructed multivariable-adjusted linear regression models to determine the association between race/ethnicity and CRF, which was defined as peak oxygen uptake (ml/kg/min). Black participants had the lowest CRF (blacks: 26.3 ± 10.2; whites: 29.0 ± 9.8; Hispanics: 29.1 ± 10.0ml/kg/min). In multivariate analysis, both black and Hispanic participants had lower CRF after adjustment for age and gender (blacks: Std β=-0.15; p value ≤0.0001, Hispanics: Std β=-0.05, p value= 0.01; ref group: whites). However, this association was considerably attenuated for black (Std β=-0.04, p value= 0.03) and no longer significant for Hispanic ethnicity (p value= 0.56) after additional adjustment for BMI, lifestyle factors, SES, and CV risk factors. Additional adjustment for stroke volume did not substantially change the association between black race/ethnicity and CRF (Std β=-0.06, p value= 0.01). In conclusion, BMI, lifestyle, SES, and traditional risk factor burden are important determinants of ethnicity-based differences in CRF.

Premature cardiovascular disease following a history of hypertensive disorder of pregnancy

BackgroundFollowing an episode of hypertensive disorder of pregnancy (HDP) women have an increased risk of cardiovascular disease over their lifetime. At the time of acute coronary syndrome we compared clinical information between women with and without a history of hypertension in pregnancy to gain further insight into the pathophysiology of cardiovascular disease in this population. MethodsGENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond—PRemature Acute Coronary SYdrome) is a prospective multicenter study, with recruitment between January 2009 and April 2013, including 242 parous women with premature acute coronary syndrome. ResultsThe median age was 50years (IQR 6) and HDP was common; 43 (17.8%) women had prior gestational hypertension, 33 (13.6%) preeclampsia and 166 (68.6%) a prior normotensive pregnancy. Women with a history of HDP commonly had chronic hypertension and diabetes and those presenting with ST-elevation myocardial infarction were more likely to have a history of preeclampsia (aOR 3.12, 95% CI 1.22–8.01) than were women with prior normotensive pregnancies. Neither gestational hypertension (aOR 1.40, 95% CI 0.60–3.26) nor preeclampsia (aOR 0.63, 95% CI 0.23–1.74) was associated with a higher composite risk of three-vessel, left main or proximal left anterior descending coronary disease. ConclusionIn this study of women with premature cardiovascular disease, ST-elevation myocardial infarction was associated with a history of preeclampsia possibly because of persistent endothelial dysfunction. High-risk coronary lesions on angiography did not appear to have an association with preeclampsia or gestational hypertension despite a high burden of traditional risk factors.

Oxidative stress and thromboxane-dependent platelet activation in inflammatory bowel disease: effects of anti-TNF-α treatment.

Patients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism and coronary artery disease despite having a lower burden of traditional risk factors. Platelets from IBD patients release more soluble CD40 ligand (CD40L), and this has been implicated in IBD platelet hyper-activation. We here measured the urinary F2-isoprostane 8-iso-prostaglandin (PG)2α (8-iso-PGF2α), urinary 11-dehydro-thromboxane (TX) B2 (11-dehydro-TXB2) and plasma CD40L in IBD patients, and explored the in vitro action of anti-tumour necrosis factor (TNF)-α antibody infliximab on IBD differentiating megakaryocytes. Urinary and blood samples were collected from 124 IBD patients and 37 healthy subjects. Thirteen IBD patients were also evaluated before and after 6-week infliximab treatment. The in vitro effect of infliximab on patient-derived megakaryocytes was evaluated by immunoflorescence microscopy and by flow cytometry. IBD patients had significantly (p<0.0001) higher urinary 8-iso-PGF2α and 11-dehydro-TXB2 as well as plasma CD40L levels than controls, with active IBD patients displaying higher urinary and plasma values when compared to inactive patients in remission. A 6-week treatment with infliximab was associated with a significant reduction of the urinary excretion of 8-iso-PGF2α and 11-dehydro-TXB2 (p=0.008) and plasma CD40L (p=0.001). Infliximab induced significantly rescued pro-platelet formation by megakaryocytes derived from IBD patients but not from healthy controls. Our findings provide evidence for enhanced in vivo TX-dependent platelet activation and lipid peroxidation in IBD patients. Anti-TNF-α therapy with infliximab down-regulates in vivo isoprostane generation and TX biosynthesis in responder IBD patients. Further studies are needed to clarify the implication of infliximab induced-proplatelet formation from IBD megakaryocytes.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

OP0293 Implementation of the Eular Recommendations for Cardiovascular Risk Management in Germany: Results of A Cross-Sectional Epidemiologic Study

BackgroundThe increased cardiovascular (CV) risk of patients suffering from rheumatoid arthritis (RA) is well documented and can partially be explained by traditional risk factors [1]. Available evidence supports inflammatory arthritis...

Abstract P258: Traditional Risk Factors and a Genetic Risk Score Are Associated with Age of First Acute Coronary Syndrome

Background: Early onset myocardial infarction (MI) is frequently attributed to genetic factors that may accelerate the atherosclerotic process. However, early MI may also occur due to a high burden of traditional risk factors. We sought to examine the association between traditional risk factors as well as a genetic risk score on the age of a first acute coronary syndrome (ACS). Methods and Results: We included 460 participants (mean age 59 +/- 12 years, 22.4% female) with a first ACS enrolled in the Recurrence and Inflammation in the Acute Coronary Syndromes (RISCA) cohort. Participants were genotyped for 30 single nucleotide polymorphisms identified from prior myocardial infarction genome-wide association studies to construct a multilocus genetic risk score (GRS). Linear regression models were fit to estimate the association between traditional risk factors (TRFs) and the GRS with age of first ACS. Several TRFs were significantly associated with earlier age of first ACS (all β coefficients in years; p&lt;0.05 for all) : male sex [β=-6.9 (95%CI -9.7,-4.1)], current cigarette smoking [β=-8.1 (95% confidence interval [CI] -10.0, -6.1)], overweight (BMI&gt;25) [β=-2.6 (95%CI -4.8, -0.3)] and obesity (BMI&gt;30) [β=-5.24 (95%CI -7.9, -2.6)]. Use of hormone replacement therapy [β=-4.3 (95%CI -8.4, -0.3) ] and aspirin use were also associated with age of first ACS [β=3.7 (95%CI 0.3, 7.0)]. After multivariable adjustment for TRFs, a one standard deviation increment in the GRS was associated with a 1.0 (95%CI 0.1-2.0) year earlier age of first ACS. Conclusion: Among individuals with a first ACS, a GRS composed of 30 SNPs is associated with a younger age of presentation. Although common genetic predisposition modestly contributes to earlier ACS, a heavy burden of traditional risk factors is strongly associated with markedly earlier ACS.

Risk of cardiovascular disease in inflammatory bowel disease.

Abundant scientific evidence supporting an association between inflammatory bowel disease (IBD) and venous thromboembolic events, caused by an IBD related hypercoagulability, is acknowledged and thromboprophylactic treatment strategies are now implemented in the management of IBD patients. In contrary, the risk of arterial thromboembolic disease, as ischemic heart disease, cerebrovascular events, and mesenteric ischemia in patients with IBD remains uncertain and the magnitude of a potentially increased risk is continuously debated, with ambiguous risk estimates among studies. The evident role of inflammation in the pathogenesis of atherosclerosis forms the basis of a biological plausible link; the chronic systemic inflammation in IBD patients increases the risk of atherosclerosis and thereby the risk of thrombotic events. Further, studies have shown that the burden of traditional risk factors for atherosclerosis, such as obesity, diabetes mellitus, and dyslipidemia is lower in IBD populations, thus further strengthen the role of non-traditional risk factors, as chronic inflammation in the linking of the two disease entities. Likewise, mortality from cardiovascular disease in IBD remains questioned. The aim of the current review is to give an up-date on the existing evidence of the possible association between IBD and cardiovascular disease and to discuss traditional and non-traditional risk factors.

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

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