Clinical Cardiovascular Disease Events Research Articles

Nut consumption for the primary prevention of cardiovascular disease.

Nuts contain a number of nutritional attributes which may be cardioprotective. A number of epidemiological studies have shown that nut consumption may have a beneficial effect on people who have cardiovascular disease (CVD) risk factors. However, results from randomised controlled trials (RCTs) are less consistent. To determine the effectiveness of nut consumption for the primary prevention of CVD. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science Core Collection, CINAHL, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA) and Health Economics Evaluations Database (HEED) up to 30 July 2015. We searched trial registers and reference lists of reviews for further studies. We did not apply any language restrictions. We included RCTs of dietary advice to increase nut consumption or provision of nuts to increase consumption lasting at least three months and including healthy adults or adults at moderate and high risk of CVD. The comparison group was no intervention or minimal intervention. The outcomes of interest were CVD clinical events and CVD risk factors. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias in included trials. We included five trials (435 participants randomised) and one ongoing trial. One study is awaiting classification. All trials examined the provision of nuts to increase consumption rather than dietary advice. None of the included trials reported on the primary outcomes, CVD clinical events, but trials were small and short term. All five trials reported on CVD risk factors. Four of these trials provided data in a useable format for meta-analyses, but heterogeneity precluded meta-analysis for most of the analyses. Overall trials were judged to be at unclear risk of bias.There were variable and inconsistent effects of nut consumption on CVD risk factors (lipid levels and blood pressure). Three trials monitored adverse events. One trial reported an allergic reaction to nuts and three trials reported no significant weight gain with increased nut consumption. None of the included trials reported on other secondary outcomes, occurrence of type 2 diabetes as a major risk factor for CVD, health-related quality of life and costs. Currently there is a lack of evidence for the effects of nut consumption on CVD clinical events in primary prevention and very limited evidence for the effects on CVD risk factors. No conclusions can be drawn and further high quality longer term and adequately powered trials are needed to answer the review question.

Vitamin K for the primary prevention of cardiovascular disease.

A deficiency in vitamin K has been associated with increased calcium deposition and coronary artery calcification, which may lead to cardiovascular disease. To determine the effectiveness of vitamin K supplementation as a single nutrient supplement for the primary prevention of cardiovascular disease. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8 of 12, 2014); MEDLINE (Ovid, 1946 to September week 2 2014); EMBASE Classic + EMBASE (Ovid, 1947 to September 18 2014); Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index, Science (CPCI-S) (both 1990 to 17 September 2014) on Web of Science (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database (Issue 3 of 4, 2014). We searched trial registers and reference lists of reviews for further studies. We applied no language restrictions. We included randomised controlled trials of vitamin K supplementation as a single nutrient supplement, lasting at least three months, and involving healthy adults or adults at high risk of cardiovascular disease. The comparison group was no intervention or placebo. The outcomes of interest were cardiovascular disease clinical events and cardiovascular disease risk factors. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias. We included only one small trial (60 participants randomised) which overall was judged to be at low risk of bias. The study examined two doses of menaquinone (vitamin K2) over 3 months in healthy participants aged 40 to 65 years. The primary focus of the trial was to examine the effects of menaquinone (subtype MK7) on different matrix Gla proteins (MGP - vitamin K dependent proteins in the vessel wall) at different doses, but the authors also reported blood pressure and lipid levels. The trial did not report on our primary outcomes (cardiovascular disease clinical events) as it was small, short term and conducted in healthy participants.In terms of cardiovascular disease risk factors, no effects were seen for vitamin K2 on blood pressure or lipid levels, although the trial was small and findings are limited. The trial did not report any of our other secondary outcomes. The very limited results of this review highlight the lack of evidence currently available to determine the effectiveness of vitamin K supplementation for the primary prevention of cardiovascular disease, and demonstrate the need for further high quality trials in this area.

Qigong for the primary prevention of cardiovascular disease.

Two major determinants of cardiovascular disease (CVD) are a sedentary lifestyle and stress. Qigong involves physical exercise, mind regulation and breathing control to restore the flow of Qi (a pivotal life energy). As it is thought to help reduce stress and involves exercise, qigong may be an effective strategy for the primary prevention of CVD. To determine the effectiveness of qigong for the primary prevention of CVD. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (November 2014, Issue 10 of 12); MEDLINE (Ovid) (1946 to 2014 October week 4); EMBASE Classic + EMBASE (Ovid) (1947 to 2014 November 4); Web of Science Core Collection (1970 to 31 October 2014); Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database and Health Economics Evaluations Database (November 2014, Issue 4 of 4). We searched several Asian databases (inception to July 2013) and the Allied and Complementary Medicine Database (AMED) (inception to December 2013), as well as trial registers and reference lists of reviews and articles; we also approached experts in the field and applied no language restrictions in our search. Randomised controlled trials lasting at least three months involving healthy adults or those at high risk of CVD. Trials examined any type of qigong, and comparison groups provided no intervention or minimal intervention. Outcomes of interest included clinical CVD events and major CVD risk factors. We did not include trials that involved multi-factorial lifestyle interventions or weight loss. Two review authors independently selected trials for inclusion. Two review authors extracted data from included studies and assessed the risk of bias. We identified 11 completed trials (1369 participants) and one ongoing trial. Trials were heterogeneous in participants recruited, qigong duration and length of follow-up periods. We were unable to ascertain the risk of bias in nine trials published in Chinese, as insufficient methodological details were reported and we were unable to contact the study authors to clarify this.We performed no meta-analyses, as trials were small and were at significant risk of bias. Clinical events were detailed in subsequent reports of two trials when statistically significant effects of qigong were seen for all-cause mortality, stroke mortality and stroke incidence at 20 to 30 years after completion of the trials. However, these trials were designed to examine outcomes in the short term, and it is not clear whether qigong was practised during extended periods of follow-up; therefore effects cannot be attributed to the intervention. None of the included studies reported other non-fatal CVD events.Six trials provided data that could be used to examine the effects of qigong on blood pressure. Reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were seen in three and two trials, respectively. Three trials examined the effects of qigong on blood lipids when favourable effects were seen in one trial for total cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides, and two trials showed favourable effects on high-density lipoprotein (HDL) cholesterol. The only trial considered at low risk of selection and detection bias did not demonstrate statistically significant effects on CVD risk factors with qigong, but this study was small and was underpowered. None of the included studies reported incidence of type 2 diabetes (T2D), adverse events, quality of life or costs. Currently, very limited evidence is available on the effectiveness of qigong for the primary prevention of CVD. Most of the trials included in this review are likely to be at high risk of bias, so we have very low confidence in the validity of the results. Publication of the ongoing trial will add to the limited evidence base, but further trials of high methodological quality with sufficient sample size and follow-up are needed to be incorporated in an update of this review before the effectiveness of qigong for CVD prevention can be established.

Haeme oxygenase signalling pathway: implications for cardiovascular disease.

Evidence now points to the haeme oxygenase (HO) pathway as a possible actor in modulating risk for cardiovascular disease (CVD). In particular, the HO pathway may represent a key endogenous modulator of oxidative, inflammatory, and cytotoxic stress while also exhibiting vasoregulatory properties. In this review, we summarize the accumulating experimental and emerging clinical data indicating how activity of the HO pathway and its products may play a role in mechanisms underlying the development of CVD. We also identify gaps in the literature to date and suggest future directions for investigation. Because HO pathway activity can be influenced not only by genetic traits and environmental stimuli but also by a variety of existing pharmacologic interventions, the pathway could serve as a prime target for reducing the overall burden of CVD. Further work is needed to determine the role of HO pathway products as possible prognostic markers of risk for clinical CVD events and the extent to which therapeutic augmentation or inhibition of HO pathway activity could serve to modify CVD risk.

Endogenous testosterone and its relationship to preclinical and clinical measures of cardiovascular disease in the atherosclerosis risk in communities study.

Epidemiologic studies suggest that endogenous testosterone (T) levels in males may be implicated in cardiovascular disease (CVD), however further clarification is needed. We assessed the cross-sectional relationship between endogenous plasma T and mean carotid intima media thickness (cIMT), and the longitudinal relationship with incident clinical CVD events, cardiac mortality, and all-cause mortality using male participants in the Atherosclerosis Risk in Communities (ARIC) study. This study involved a subset of men from visit 4 of the ARIC study. The study was conducted in a community based cohort. Males who provided a morning blood sample excluding those taking androgen therapy, with prevalent coronary heart disease (CHD), stroke, or heart failure (HF) (n = 1558). None. Plasma T by liquid chromatography mass spectrometry and carotid IMT using high resolution B-mode ultrasound were obtained at visit 4. Incident CHD, HF, cardiac mortality, and all-cause mortality were identified by surveillance through 2010 (median 12.8 years). Lower T was significantly associated with higher body mass index, greater waist circumference, diabetes, hypertension, lower HDL, and never smoking (P = 0.01). T was not associated with mean cIMT in unadjusted or adjusted analyses. Following multivariable adjustment, there was no association of quartile (Q) of T with incident CHD [hazard ratio (HR) = 0.87 (95% CI = 0.60-1.26) for Q1; 0.97 (95% CI = 0.69-1.38) for Q2; 0.97 (95% CI = 0.69-1.36) for Q3 compared to reference of Q4] or for incident HF [HR = 0.77 (95% CI = 0.46-1.29) for Q1; 0.72 (95% CI = 0.43-1.21) for Q2; 0.87 (95% CI = 0.53-1.42) for Q3 compared to reference of Q4]. Similarly there was no association of Q of T with mortality or cardiac-associated mortality. Low male plasma T is cross-sectionally associated with key CVD risk factors, but after adjustment there was no association with mean cIMT, incident cardiac events, or mortality. Our results are reassuring that neither high nor low T levels directly predict atherosclerosis, but are a marker for other cardiovascular risk factors.

Cardiovascular diseases and vulnerable plaques: data, modeling, predictions and clinical applications.

Introduction Two symposia on “cardiovascular diseases and vulnerable plaques” Cardiovascular disease (CVD) is the leading cause of death worldwide. Huge effort has been made in many disciplines including medical imaging, computational modeling, bio- mechanics, bioengineering, medical devices, animal and clinical studies, population studies as well as genomic, molecular, cellular and organ-level studies seeking improved methods for early detection, diagnosis, prevention and treatment of these diseases [1-14]. However, the mechanisms governing the initiation, progression and the occurrence of final acute clinical CVD events are still poorly understood. A large number of victims of these dis- eases who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs [8,9]. Most cardiovascular diseases are associated with vulnerable plaques. A grand challenge here is to develop new imaging techniques, predictive methods and patient screening tools to identify vulnerable plaques and patients who are more vulnerable to plaque rupture and associated clinical events such as stroke and heart attack, and recommend proper treatment plans to prevent those clinical events from happening. Articles in this special issue came from two symposia held recently focusing on “Cardio-vascular Diseases and Vulnerable Plaques: Data, Modeling, Predictions and Clinical Applications.” One was held at Worcester Polytechnic Institute (WPI), Worcester, MA, USA, July 13-14, 2014, right after the 7th World Congress of Biomechanics. This symposium was endorsed by the World Council of Biomechanics, and partially supported by a grant from NIH-National Institute of Biomedical Image and Bioengineering. The other was held at Southeast University (SEU), Nanjing, China, April 18-20, 2014.

Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease.

Cardiovascular disease (CVD) remains the number one cause of death and disability worldwide and public health interventions focus on modifiable risk factors, such as diet. Coenzyme Q10 (CoQ10) is an antioxidant that is naturally synthesised by the body and can also be taken as a dietary supplement. Studies have shown that a CoQ10 deficiency is associated with cardiovascular disease. To determine the effects of coenzyme Q10 supplementation as a single ingredient for the primary prevention of CVD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 11); MEDLINE (Ovid, 1946 to November week 3 2013); EMBASE (Ovid, 1947 to 27 November 2013) and other relevant resources on 2 December 2013. We applied no language restrictions. Randomised controlled trials (RCTs) lasting at least three months involving healthy adults or those at high risk of CVD but without a diagnosis of CVD. Trials investigated the supplementation of CoQ10 alone as a single supplement. The comparison group was no intervention or placebo. The outcomes of interest were CVD clinical events and major CVD risk factors, adverse effects and costs. We excluded any trials involving multifactorial lifestyle interventions to avoid confounding. Two authors independently selected trials for inclusion, abstracted data and assessed the risk of bias.We contacted authors for additional information where necessary. We identified six RCTs with a total of 218 participants randomised, one trial awaiting classification and five ongoing trials. All trials were conducted in participants at high risk of CVD, two trials examined CoQ10 supplementation alone and four examined CoQ10 supplementation in patients on statin therapy; we analysed these separately. All six trials were small-scale, recruiting between 20 and 52 participants; one trial was at high risk of bias for incomplete outcome data and one for selective reporting; all studies were unclear in the method of allocation and therefore for selection bias. The dose of CoQ10 varied between 100 mg/day and 200 mg/day and the duration of the interventions was similar at around three months.No studies reported mortality or non-fatal cardiovascular events. None of the included studies provided data on adverse events.Two trials examined the effect of CoQ10 on blood pressure. For systolic blood pressure we did not perform a meta-analysis due to significant heterogeneity. In one trial CoQ10 supplementation had no effect on systolic blood pressure (mean difference (MD) -1.90 mmHg, 95% confidence interval (CI) -13.17 to 9.37, 51 patients randomised). In the other trial there was a statistically significant reduction in systolic blood pressure (MD -15.00 mmHg, 95% CI -19.06 to -10.94, 20 patients randomised). For diastolic blood pressure we performed a random-effects meta-analysis, which showed no evidence of effect of CoQ10 supplementation when these two small trials were pooled (MD -1.62 mmHg, 95% CI -5.2 to 1.96).One trial (51 patients randomised) looked at the effect of CoQ10 on lipid levels. The trial showed no evidence of effect of CoQ10 supplementation on total cholesterol (MD 0.30 mmol/L, 95% CI -0.10 to 0.70), high-density lipoprotein (HDL)-cholesterol (MD 0.02 mmol/L, 95% CI -0.13 to 0.17) or triglycerides (MD 0.05 mmol/L, 95% CI -0.42 to 0.52).Of the four trials that investigated CoQ10 supplementation in patients on statin therapy, three of them showed that simultaneous administration of CoQ10 did not significantly influence lipid levels or systolic blood pressure levels between the two groups. The fourth trial showed a significant increase in the change in total and low-density lipoprotein (LDL)-cholesterol at three months across the four arms of the trial (α-tocopherol, CoQ10, CoQ10 + α-tocopherol and placebo), however the way in which the data were presented meant that we were unable to determine if there was any significant difference between the CoQ10 only and placebo arms. In contrast, there was no significant difference in the change in HDL-cholesterol and triglycerides after three months between the four arms of the trial. There are very few studies to date examining CoQ10 for the primary prevention of CVD. The results from the ongoing studies will add to the evidence base. Due to the small number of underpowered trials contributing to the analyses, the results presented should be treated with caution and further high quality trials with longer-term follow-up are needed to determine the effects on cardiovascular events.

Cochrane Corner: Yoga to prevent cardiovascular disease

It is widely accepted that both stress and physical inactivity are important risk factors for cardiovascular disease (CVD) [1]. Strategies which promote a healthy lifestyle, including exercise and stress management, have been shown to be beneficial in terms of reducing CVD risk factors [1]. Yoga has been demonstrated to reduce stress [2] and the holding of poses that is involved provides surprising robust exercise [3] and so, theoretically, yoga could be effective as a primary prevention intervention for CVD. This Cochrane review included all controlled trials of any type of yoga lasting at least three months, with a comparison group of either no or minimal intervention [4]. 11 trials with around 800 participants in total, and two ongoing studies were included, and clinical CVD events and major CVD risk factors were the outcomes assessed. Around half of the participants recruited to the studies were considered to be at high risk of CVD, and around half were considered to be healthy. None of the included studies provided CVD or all-cause mortality data, or reported non-fatal CVD endpoints. However, in terms of CVD risk factors, 9 of the 11 studies measured blood pressure, and although meta-analysis was not possible for systolic blood pressure, all but 1 study reported that yoga led to a reduction, which was statistically significant in 3 studies. Metaanalysis was possible for diastolic blood pressure as there was less heterogeneity between studies, and yoga was found to significantly lower diastolic blood pressure (MD 2.90, 95% CI 4.52 to 1.28). Five trials measured lipid levels. The data for total cholesterol could not be pooled for meta-analysis, but two of the studies found A R T I C L E I N F O

Transcendental meditation for the primary prevention of cardiovascular disease.

A major determinant in cardiovascular disease (CVD) is stress. As transcendental meditation (TM) is thought to help in lowering negative stress indicators, it may be a beneficial strategy for the primary prevention of CVD. To determine the effectiveness of TM for the primary prevention of CVD. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 10); MEDLINE (Ovid) (1946 to week three November 2013); EMBASE Classic and EMBASE (Ovid) (1947 to week 48 2013); ISI Web of Science (1970 to 28 November 2013); and Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment Database and Health Economics Evaluations Database (November 2013). We also searched the Allied and complementary Medicine Database (AMED) (inception to January 2014) and IndMed (inception to January 2014). We handsearched trial registers and reference lists of reviews and articles and contacted experts in the field. We applied no language restrictions. We included randomised controlled trials (RCTs) of at least three months' duration involving healthy adults or adults at high risk of CVD. Trials examined TM only and the comparison group was no intervention or minimal intervention. We excluded trials that involved multi-factorial interventions. Outcomes of interest were clinical CVD events (cardiovascular mortality, all-cause mortality and non-fatal events) and major CVD risk factors (e.g. blood pressure and blood lipids, occurrence of type 2 diabetes, quality of life, adverse events and costs). Two authors independently selected trials for inclusion, extracted data and assessed the risk of bias. We identified four trials (four papers) (430 participants) for inclusion in this review. We identified no ongoing studies. The included trials were small, short term (three months) and at risk of bias. In all studies, TM was practised for 15 to 20 minutes twice a day.None of the included studies reported all-cause mortality, cardiovascular mortality or non-fatal endpoints as trials were short term, but one study reported survival rate three years after the trial was completed. In view of the considerable statistical heterogeneity between the results of the studies for the only outcomes reported, systolic blood pressure (I(2) = 72%) and diastolic blood pressure (I(2) = 66%), we decided not to undertake a meta-analysis. None of the four trials reported blood lipids, occurrence of type 2 diabetes, adverse events, costs or quality of life. Currently, there are few trials with limited outcomes examining the effectiveness of TM for the primary prevention of CVD. Due to the limited evidence to date, we could draw no conclusions as to the effectiveness of TM for the primary prevention of CVD. There was considerable heterogeneity between trials and the included studies were small, short term and at overall serious risk of bias. More and larger long-term, high-quality trials are needed.

Abstract 15615: Eligibility for Lipid Lowering Therapy Based on AHA/ACC Risk Score, Coronary Artery Calcification, and CVD Events- National Implications for the Appropriate Use of Preventive Pharmacotherapy: Multi-Ethnic Study of Atherosclerosis (MESA)

Background: It is estimated that according to ACC-AHA guidelines for cholesterol management an additional 12.8 million adults including 10.4 million for primary prevention are considered for moderate-high intensity statin therapy. We sought to determine whether coronary artery calcium (CAC) testing might identify individuals who are expected to derive the most, and the least, benefit from the prescribed pharmacotherapy. Methods: MESA is a longitudinal, population-based study of 6,814 men and women aged 45-84 without clinical cardiovascular disease (CVD) at enrollment. The following participants were excluded from the analysis: 1100 (16%) on lipid lowering medication, 87 individuals (1.3%) with absent LDL levels, 26 (0.4%) with missing risk factors for calculation of 10-yr risk of ASCVD based on the new pooled-cohort equations as well as 634 (9.3%) aged >75 years. Results: The final study population consisted of 4,967 individuals (59±9 years, 47% males). Overall 255 (5.1%) hard CVD events were noted in follow-up of median 10.3 years (IQR=9.7-10.8). Based on the new guidelines (figure), 2449 (49%) were considered candidates for moderate-high intensity statin therapy at baseline. Of these, 41% had CAC=0 and had 5.2 CVD events/1000 person-years and 29% had CAC>100 and they had 15.2 events/1000 person-years. Among the 610 individuals who would be considered candidates for moderate intensity statin , 350 (57%) had a CAC=0 and an event rate of 1.5/1000 person year. CAC testing was similarly able to risk stratify individuals across increasing levels (quartiles) of ASCVD risk >7.5% (figure). Conclusion: Within MESA, nearly half of patients considered for statin therapy based on the new guidelines had CAC=0, and experienced a very low event rate and subsequent high number needed to treat to prevent one event. Our study findings suggest that CAC further refines the estimate of CVD risk and may facilitate informed shared decision-making regarding statin treatment.

Abstract 16947: A Meta-Synthesis on Usefulness of Stress Reduction with Meditation in the Prevention and Treatment of Cardiovascular Disease

Introduction: Epidemiological research has documented that psychosocial stress is a major risk factor for atherosclerotic cardiovascular disease (CVD). In providing effective health education to patients with CVD, nurses and other health professionals require evidence-based information on behavioral methods to reduce stress for primary and secondary prevention of CVD. Previously published trials suggest that selected stress reduction methods, including meditation may modify CVD risk factors, quality of life, morbidity and mortality. Hypothesis: Stress reduction with meditation may contribute to the management of psychosocial stress, hypertension, metabolic syndrome, chronic CVD, nonfatal/fatal CVD clinical events and associated health care costs. Methods: We performed a meta-synthesis (qualitative review) of published biomedical literature for randomized controlled trials, meta-analyses and professional guidelines on the effects of meditation on CVD and its risk factors. Results: The two most widely studied stress reduction - meditation approaches in CVD were the Transcendental Meditation (TM) technique and mindfulness meditation There were 11 RCTs, two meta-analyses and one American Heart Association scientific statement on TM and blood pressure that suggest TM is clinically useful in lowering high BP, short and long-term, in diverse populations. Other risk factors showing beneficial responses to TM were anxiety, insulin resistance, smoking and surrogate markers for CVD. RCTs and meta-analyses report significant risk reductions for myocardial infarction, stroke and mortality over 5-8 years. In patients with CVD, mindfulness meditation was associated with beneficial psychological effects; however, in meta-analyses of physical parameters of CVD, effects were not yet well-established. Conclusion: Available evidence suggests that meditation may be useful in the behavioral interventions for cardiovascular health and quality of life. Both Transcendental Meditation and mindfulness meditation practices show beneficial effects on psychosocial stress factors. Substantial evidence indicates that TM practice is associated with reductions in hypertension, other CVD risk factors, and rates of CVD morbidity and mortality.

Associations between Clinical Cardiovascular Disease Events and Long-Term Exposure to Air Pollutants in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

MESA Air prospectively assesses the relationship between individual-level estimates of long-term air pollution exposures and the incidence of cardiovascular disease (CVD) events. We present preliminary findings for analyses of the association between long-term exposure to fine particulate matter (PM2.5), oxides of nitrogen (NOx), and black carbon (BC) with incidence of CVD events. We estimate the association between long-term exposures and risk of CVD events using proportional hazards models. Two-week average predictions from spatiotemporal prediction models are aggregated to create two-year moving average air pollution concentrations to capture secular trends in long-term exposures. Primary analyses adjust for city, individual socio-economic status (SES), smoking, adiposity, physical activity, family history of CVD, HDL and total cholesterol, and employment outside of the home. Additionally, median household income and baseline SES z-score at the census tract are included. Our study was designed to be adequately powered based on 1200 events accrued over a 10-year period in the cohort. At baseline, the average age of enrolled participants eligible for this analysis was 62 years. During the average 9.1 years of follow-up from recruitment (2000-2002) through 2011, 634 of the 6764 participants experienced a CVD event. In interim analyses, PM2.5 is significantly associated with increased risk of CVD events (HR: 1.08 per 1 µg/m3, 95% CI: 1.01-1.14). NOx is associated with increased risk, but this association is not statistically significant (HR: 1.06 per 10 ppb, 95% CI: 0.97-1.15). BC shows no association (HR 0.99 per 1 10-6/m, 95% CI 0.93-1.05). Preliminary findings support the relationship between air pollution and CVD events despite slower than expected events accrual during the study. Use of time-varying exposures accurately reflects secular trends in long-term exposures and is strongly associated with incidence of CVD. Further follow-up will allow for greater power.

Significance of a Positive Family History for Coronary Heart Disease in Patients With a Zero Coronary Artery Calcium Score (from the Multi-Ethnic Study of Atherosclerosis)

Although a coronary artery calcium (CAC) score of 0 is associated with a very low 10-year risk for cardiac events, this risk is nonzero. Subjects with a family history of coronary heart disease (CHD) has been associated with more subclinical atherosclerosis than subjects without a family history of CHD. The purpose of this study was to assess the significance of a family history for CHD in subjects with a CAC score of 0. The Multi-Ethnic Study of Atherosclerosis cohort includes 6,814 participants free of clinical cardiovascular disease (CVD) at baseline. Positive family history was defined as reporting a parent, sibling, or child who had a heart attack. Time to incident CHD or CVD event was modeled using the multivariable Cox regression; 3,185 subjects were identified from the original Multi-Ethnic Study of Atherosclerosis cohort as having a baseline CAC score of 0 (mean age 58 years, 37% men). Over a median follow-up of 10 years, 101 participants (3.2%) had CVD events and 56 (1.8%) had CHD events. In age- and gender-adjusted analyses, a family history of CHD was associated with an ∼70% increase in CVD (hazard ratio 1.73, 95% confidence interval 1.17 to 2.56) and CHD (hazard ratio 1.72, 95% confidence interval 1.01 to 2.91) events. CVD events remained significant after further adjustment for ethnicity, risk factors, and baseline medication use. In conclusion, asymptomatic subjects with a 0 CAC score and a positive family history of CHD are at increased risk for CVD and CHD events compared with those without a family history of CHD, although absolute event rates remain low.

Left Ventricular Geometry and All-cause Mortality in Advanced Age

Abnormalities of cardiac structure and function are common in a wide range of populations including those with and without established clinical cardiovascular disease (CVD). This study reports the prevalence of left ventricular hypertrophy (LVH), the four patterns of LV geometry and establishes clinical characteristics and five-year outcomes of each group in people of advanced age. A study conducted in general practices and Māori Health Services in three New Zealand North Island locations. One hundred participants had a full clinical echocardiogram performed and analysed in 2008 by one experienced cardiologist blinded to the participant's clinical history. Two-thirds of the participants had CVD. Thirty-two participants had echocardiographic LVH. Those with LVH had higher left atrial area [median (IQR) 26.4cm(2) (10.9) vs. 22.0cm(2) (7.0), p<0.01] and E/e' [median (IQR) 13 (6.8) vs.10.8 (4.1), p=0.01] than those without LVH. Of those with LVH, 10 demonstrated concentric hypertrophy (CH) and 22 eccentric hypertrophy (EH); 12 concentric remodelling (CR) and 40 normal geometry (NG). Both CR and EH were independently associated with higher risk of all-cause mortality (p<0.01) and hospital admissions (p<0.05) than those with NG. Those with EH also had a higher risk of CVD events (p=0.029). Despite a high prevalence of CVD and hypertension in this sample, half had normal LV geometry. Concentric remodelling and eccentric hypertrophy were associated with higher mortality and adverse CVD outcomes in people of advanced age.

Lipoproteins as biomarkers and therapeutic targets in the setting of acute coronary syndrome.

The period following an acute coronary syndrome (ACS) represents a critical time frame with a high risk for recurrent events and death. The pathogenesis of this increase in clinical cardiovascular disease events after ACS is complex, with molecular mechanisms including increased thrombosis and inflammation. Dyslipoproteinemia is common in patients with ACS and predictive of recurrent cardiovascular disease events after presentation with an ACS event. Although randomized clinical trials have provided fairly convincing evidence that high-dose statins reduce the risk of recurrent cardiovascular events after ACS, there remain questions about how aggressively to reduce low-density lipoprotein cholesterol levels in ACS. Furthermore, no other lipid-related interventions have yet been proven to be effective in reducing major cardiovascular events after ACS. Here, we review the relationship of lipoproteins as biomarkers to cardiovascular risk after ACS, the evidence for lipid-targeted interventions, and the potential for novel therapeutic approaches in this arena.

Increased arterial inflammation relates to high-risk coronary plaque morphology in HIV-infected patients.

Mechanisms predisposing HIV-infected patients to increased cardiovascular disease (CVD) risk remain unclear. To determine the interrelationship between arterial inflammation and high-risk coronary plaque morphology in HIV-infected patients with subclinical coronary atherosclerosis. Forty-one HIV-infected patients on stable antiretroviral therapy without known CVD but with atherosclerotic plaque on coronary CT angiography were evaluated with F-FDG-PET. Patients were stratified into 2 groups based on relative degree of arterial inflammation [aortic target-to-background ratio (TBR)]. High-risk coronary atherosclerotic plaque morphology features were compared between groups. HIV-infected patients with higher and lower TBRs were similar with respect to traditional CVD risk parameters. Among HIV-infected patients with higher TBR, an increased percentage of patients demonstrated at least 1 low-attenuation coronary atherosclerotic plaque (40% vs. 10%, P = 0.02) and at least 1 coronary atherosclerotic plaque with both low attenuation and positive remodeling (35% vs. 10%, P = 0.04). Moreover, in the higher TBR group, both the number of low-attenuation plaques per patient (P = 0.02) and the number of vulnerability features in the most vulnerable plaque (P = 0.02) were increased. TBR grouping remained significantly related to the number of low-attenuation plaques/subject (β = 0.35, P = 0.004), controlling for age, gender, low-density lipoprotein, duration of HIV, and CD4. These data demonstrate a relationship between arterial inflammation on F-FDG-PET and high-risk coronary atherosclerotic plaque features among HIV-infected patients with subclinical coronary atherosclerosis. Further studies are needed to determine whether arterial inflammation and related high-risk coronary morphology increase the risk of clinical CVD events in the HIV population.

Yoga for the primary prevention of cardiovascular disease.

A sedentary lifestyle and stress are major risk factors for cardiovascular disease (CVD). Since yoga involves exercise and is thought to help in stress reduction it may be an effective strategy in the primary prevention of CVD. To determine the effect of any type of yoga on the primary prevention of CVD. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11) inThe Cochrane Library;MEDLINE (Ovid) (1946 to November Week 3 2013); EMBASE Classic + EMBASE (Ovid) (1947 to 2013 Week 48); Web of Science (Thomson Reuters) (1970 to 4 December 2013); Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database and Health Economics Evaluations Database (Issue 4 of 4, 2013) inThe Cochrane Library. We also searched a number of Asian databases and the Allied and Complementary Medicine Database (AMED) (inception to December 2012).We searched trial registers and reference lists of reviews and articles, and approached experts in the field. We applied no language restrictions. Randomised controlled trials lasting at least three months involving healthy adults or those at high risk of CVD. Trials examined any type of yoga and the comparison group was no intervention or minimal intervention. Outcomes of interest were clinical CVD events and major CVD risk factors. We did not include any trials that involved multifactorial lifestyle interventions or weight loss. Two authors independently selected trials for inclusion, extracted data and assessed the risk of bias. We identified 11 trials (800 participants) and two ongoing studies. Style and duration of yoga differed between trials. Half of the participants recruited to the studies were at high risk of CVD. Most of studies were at risk of performance bias, with inadequate details reported in many of them to judge the risk of selection bias.No study reported cardiovascular mortality, all-cause mortality or non-fatal events, and most studies were small and short-term. There was substantial heterogeneity between studies making it impossible to combine studies statistically for systolic blood pressure and total cholesterol. Yoga was found to produce reductions in diastolic blood pressure (mean difference (MD) -2.90 mmHg, 95% confidence interval (CI) -4.52 to -1.28), which was stable on sensitivity analysis, triglycerides (MD -0.27 mmol/l, 95% CI -0.44 to -0.11) and high-density lipoprotein (HDL) cholesterol (MD 0.08 mmol/l, 95% CI 0.02 to 0.14). However, the contributing studies were small, short-term and at unclear or high risk of bias. There was no clear evidence of a difference between groups for low-density lipoprotein (LDL) cholesterol (MD -0.09 mmol/l, 95% CI -0.48 to 0.30), although there was moderate statistical heterogeneity. Adverse events, occurrence of type 2 diabetes and costs were not reported in any of the included studies. Quality of life was measured in three trials but the results were inconclusive. The limited evidence comes from small, short-term, low-quality studies. There is some evidence that yoga has favourable effects on diastolic blood pressure, HDL cholesterol and triglycerides, and uncertain effects on LDL cholesterol. These results should be considered as exploratory and interpreted with caution.

Adverse pregnancy outcomes and subsequent risk of cardiovascular disease in women with systemic lupus erythematosus

Background/objectivePatients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcomes and cardiovascular disease (CVD). The objective of this exploratory study was to investigate the association between...

Abstract P447: Cellular Adhesion Molecules: Early Indicators of Subsequent Clinical Cardiovascular Disease Events in a Young Adult Population. The CARDIA Study.

Background: Cellular adhesion molecules (CAM) have a central role in the accumulation of circulating leukocytes at sites of vascular injury, infection and/ inflammation, and have been associated with the development of atherosclerotic plaque and coronary artery disease in mature adults. Objective: To test the hypothesis that higher overall circulating CAM levels in young adults predict cardiovascular disease (CVD) events over the next 18 years. Method: We measured several circulating CAM molecules (ICAM-1, P-selectin, E-selectin and VCAM) in the Coronary Artery Risk Development in Young Adults (CARDIA) study at exam year 7 (1992-93, black and white men and women, CVD-free, mean age 32, range 25-37 years, n=2428) and monitored incident CVD events (n=70, including coronary heart disease, stroke, and heart failure, adjudicated based on medical records) through exam year 25, mean age of 50 years. We ranked each CAM in quintiles (coded 0-4) and summed the ranks across CAMs into an index to examine the association with incident CVD with Cox regression models. Results: Unadjusted cumulative CVD event rates were 1.6% (sum of CAM quartile ranks 0-8: 22 events in 1353 participants), 2.3% (sum of ranks 9-12: 29/813), and 7.3% (sum of ranks 13-16: 19/262). In proportional hazards regression analysis adjusted for year 7 age, sex, race, clinic, education, smoking, diet, physical activity, body mass index, blood pressure, blood lipids, and blood glucose, sum of ranks 13-16 were associated with a higher risk of CVD compared to the referent (rank sum 0-8) (See Table). Conclusion: High levels of circulating CAMs at an early stage of adulthood (mean age 32, range 25-37 years) were associated with an increased risk of incident CVD events. CAMs may be an early biomarker for development of subclinical CVD, even in CVD-free young adults with low atherosclerosis burden and decades prior to the development of clinical CVD.

Association of exhaled carbon monoxide with subclinical cardiovascular disease and their conjoint impact on the incidence of cardiovascular outcomes

Whereas endogenous carbon monoxide (CO) is cytoprotective at physiologic levels, excess CO concentrations are associated with cardiometabolic risk and may represent an important marker of progression from subclinical to clinical cardiovascular disease (CVD). In 1926 participants of the Framingham Offspring Study (aged 57 ± 10 years, 46% women), we investigated the relationship of exhaled CO, a surrogate of blood CO concentration, with both prevalent subclinical CVD and incident clinical CVD events. Presence of subclinical CVD was determined using a comprehensive panel of diagnostic tests used to assess cardiac and vascular structure and function. Individuals with the highest (>5 p.p.m.) compared with lowest (≤4 p.p.m.) CO exposure were more likely to have subclinical CVD [odds ratios (OR): 1.67, 95% CI: 1.32-2.12; P < 0.001]. During the follow-up period (mean 5 ± 3 years), 193 individuals developed overt CVD. Individuals with both high CO levels and any baseline subclinical CVD developed overt CVD at an almost four-fold higher rate compared with those with low CO levels and no subclinical disease (22.1 vs. 6.3%). Notably, elevated CO was associated with incident CVD in the presence [hazards ration (HR): 1.83, 95% CI: 1.08-3.11; P = 0.026] but not in the absence (HR: 0.80, 95% CI: 0.42-1.53; P = 0.51) of subclinical CVD (Pinteraction = 0.019). Similarly, subclinical CVD was associated with incident CVD in the presence of high but not low CO exposure. Our findings in a community-based sample suggest that elevated CO is a marker of greater subclinical CVD burden and, furthermore, a potential key component in the progression from subclinical to clinical CVD.