Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women

Objective: To examine the association between chocolate intake and the risk of future cardiovascular events. Methods: We conducted a prospective study using data from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Habitual chocolate intake was quantified using the baseline food frequency questionnaire (1993–1997) and cardiovascular end points were ascertained up to March 2008. A systematic review was performed to evaluate chocolate consumption and cardiovascular outcomes. Results: A total of 20 951 men and women were included in EPIC-Norfolk analysis (mean follow-up 11.3±2.8 years, median 11.9 years). The percentage of participants with coronary heart disease (CHD) in the highest and lowest quintile of chocolate consumption was 9.7% and 13.8%, and the respective rates for stroke were 3.1% and 5.4%. The multivariate-adjusted HR for CHD was 0.88 (95% CI 0.77 to 1.01) for those in the top quintile of chocolate consumption (16–99 g/day) versus non-consumers of chocolate intake. The corresponding HR for stroke and cardiovascular disease (cardiovascular disease defined by the sum of CHD and stroke) were 0.77 (95% CI 0.62 to 0.97) and 0.86 (95% CI 0.76 to 0.97). The propensity score matched estimates showed a similar trend. A total of nine studies with 157 809 participants were included in the meta-analysis. Higher compared to lower chocolate consumption was associated with significantly lower CHD risk (five studies; pooled RR 0.71, 95% CI 0.56 to 0.92), stroke (five studies; pooled RR 0.79, 95% CI 0.70 to 0.87), composite cardiovascular adverse outcome (two studies; pooled RR 0.75, 95% CI 0.54 to 1.05), and cardiovascular mortality (three studies; pooled RR 0.55, 95% CI 0.36 to 0.83). Conclusions: Cumulative evidence suggests that higher chocolate intake is associated with a lower risk of future cardiovascular events, although residual confounding cannot be excluded. There does not appear to be any evidence to say that chocolate should be avoided in those who are concerned about cardiovascular risk

Association between serum secretory phospholipase A2 and risk of ischaemic stroke

Background and purpose: Previous literature has demonstrated an association between high serum levels of type II secretory phospholipase A2 (sPLA2) concentration and an increased risk of coronary artery disease. However, such association has not been established in terms of ischaemic stroke risk. The aim was to evaluate the association between both sPLA2 concentration and activity as continuous variables with risk of future ischaemic stroke. / Methods: A nested case–control study was conducted using data from the European Prospective Investigation into Cancer—Norfolk study. Cases (n = 145) in the current study were participants who developed ischaemic stroke during follow-up, with controls (n = 290) matched in a 2:1 ratio based on age and sex. Statistical analyses were performed using SPSS (version 25.0) software. Logistic regression was used to determine odds ratios (OR) and corresponding 95% confidence intervals (95% CIs) for ischaemic stroke. / Results: After adjusting for a wide array of cardiovascular confounders, sPLA2 activity was found to be associated with an increased risk of ischaemic stroke using both multiple imputations with chained equations and complete case analysis: OR 1.20 (95% CI 1.01–1.43) and OR 1.23 (95% CI 1.01−1.49), respectively. However, sPLA2 concentration was not found to be associated with increased risk of ischaemic stroke. / Conclusions: The activity of sPLA2, but not sPLA2 concentration, is associated with an increased risk of future ischaemic stroke. This finding may be significant in risk group stratification, allowing targeted prophylactic treatment, or the development of novel therapeutic agents

Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease

OBJECTIVE: In statin-treated patients with stable coronary artery disease (CAD), residual risk of cardiovascular events is partly explained by plasma levels of low-density lipoprotein cholesterol (LDL-C). This study aimed to estimate individual benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in CAD patients already treated with high-dose statin. METHODS: Individual lifetime benefit was estimated in months gain free of stroke or myocardial infarction (MI) until age 80 years. Predictions were based on two competing risk models developed in data from 4853 patients with CAD originating from the atorvastatin 80 mg arm of the Treating to New Targets (TNT) trial. The relative effect of PCSK9 inhibition was added to the models and was assumed based on average estimates from large clinical trials. We accounted for individual LDL-C levels, assuming 50% LDL-C reduction by PCSK9 inhibition and 21% cardiovascular risk reduction per mmol/L (39 mg/dL) LDL-C lowering. RESULTS: Estimated individual gain was 1.8 mmol/L (>70 mg/dL). Estimated benefit was lowest (≤5 months) in older patients (≥70 years), in particular if LDL-C and other risk factors levels were low. CONCLUSION: The individual estimated lifetime benefit from PCSK9 inhibition in patients with stable CAD on high-dose statin varied from <6 to ≥12 months free of stroke or MI. Highest benefit is expected in younger patients (age 40-60 years) with high risk factor burden and relatively high LDL-C levels. TRIAL REGISTRATION NUMBER: NCT00327691; Post-results

apoB/apoA-I Ratio and Lp(a) Associations With Aortic Valve Stenosis Incidence: Insights From the EPIC-Norfolk Prospective Population Study.

Background Apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio and lipoprotein(a) (Lp[a]) are associated with aortic valve stenosis (AVS) disease progression. Clinical characteristics such as age, sex, and presence of concomitant coronary artery disease may strongly modify these associations; however, these effects have not been well defined in longitudinal studies. We set out to assess these associations between apoB/apoA-I ratio, Lp(a), and AVS incidence in a large population study. Methods and Results We analyzed data from 17 745 participants (mean age, 59.2±9.1 years; men, 44.9%) in the EPIC-Norfolk (European Prospective Investigation Into Cancer in Norfolk Prospective Population Study) population study in whom apoB/apoA-I and Lp(a) levels were measured. Participants were identified as having incident AVS if they were hospitalized or died with AVS as an underlying cause. After a median follow-up of 19.8 years (17.9-21.0 years) there were 403 (2.2%) incident cases of AVS. The hazard ratio for AVS risk was 1.30 (95% CI, 1.19-1.41; P50 mg/dL) remained an independent risk factor for AVS after adjustment for age, sex, low-density lipoprotein cholesterol, and concomitant coronary artery disease (hazard ratio, 1.70; 95% CI, 1.33-2.19 [P<0.001]). Conclusions In this population study, apoB/apoA-I ratio was associated with risk of AVS incidence, especially in younger and female participants and those without concomitant coronary artery disease. Lp(a) was an independent risk factor for AVS incidence. Interventional trials are needed to investigate whether modulating apoB/apoA-I or lowering Lp(a) can prevent or slow down AVS

Ideal cardiovascular health and risk of cardiovascular events in the EPIC-Norfolk prospective population study.

BACKGROUND: The American Heart Association has prioritised seven cardiovascular health metrics to reduce the cardiovascular burden, including: body mass index, healthy diet, physical activity, smoking status, blood pressure, glycated haemoglobin A1c and total cholesterol. The aim of the current study was to assess the association between the American Heart Association-defined health metrics and the risk of cardiovascular events in the EPIC-Norfolk prospective study. DESIGN: Prospective cohort study. METHODS: An overall cardiovascular health score was calculated based on the number of health metrics including ideal, intermediate or poor. Cox proportional hazards models were used to describe the association of the seven metrics separately and the overall health score with risk of coronary heart disease, stroke and cardiovascular disease. A total of 10,043 participants was included in the analysis (follow-up 1993-2008). For all individual health metrics a more ideal status was associated with a lower risk of cardiovascular events. RESULTS AND CONCLUSION: As for the overall cardiovascular health score, those in the highest (i.e. healthiest) category (score 12-14) had an adjusted hazard ratio for coronary heart disease of 0.07 (95% confidence interval (CI) 0.02-0.29, P < 0.001), for stroke of 0.16 (95% CI 0.02-1.37, P = 0.09) and for cardiovascular disease of 0.07 (95% CI 0.02-0.23, P < 0.001), compared to people in the lowest (i.e. unhealthiest) category (score 0-2). The overall cardiovascular health score was strongly and inversely associated with risk of coronary heart disease, stroke and cardiovascular disease. Our data suggest that even small improvements in modifiable risk factors may lead to substantial reductions in the risks of cardiovascular events.The EPIC-Norfolk Study is funded by Cancer Research UK grant number 14136 and the Medical Research Council grant number G1000143, SL is supported by a studentship from Unilever Corporate Research, UK.This is the author accepted manuscript. The final version is available from SAGE via http://dx.doi.org/10.1177/204748731560201

Usefulness of coronary calcium scoring to myocardial perfusion SPECT in the diagnosis of coronary artery disease in a predominantly high risk population

Coronary calcium scoring (CCS) adds to the diagnostic performance of myocardial perfusion single-photon emission computed tomography (SPECT) to assess the presence of significant coronary artery disease (CAD). Patients with a high pre-test likelihood are expected to have a high CCS which potentially could enhance the diagnostic performance of myocardial perfusion SPECT in this specific patient group. We evaluated the added value of CCS to SPECT in the diagnosis of significant CAD in patients with an intermediate to high pre-test likelihood. In total, 129 patients (mean age 62.7 +/- A 9.7 years, 65 % male) with stable anginal complaints and intermediate to high pre-test likelihood of CAD (median 87 %, range 22-95) were prospectively included in this study. All patients received SPECT and CCS imaging preceding invasive coronary angiography (CA). Fractional flow reserve (FFR) measurements were acquired from patients with angiographically estimated 50-95 % obstructive CAD. For SPECT a SSS &gt; 3 was defined significant CAD. For CCS the optimal cut-off value for significant CAD was determined by ROC curve analysis. The reference standard for significant CAD was a FFR of &lt; 0.80 acquired by CA. Significant CAD was demonstrated in 64 patients (49.6 %). Optimal CCS cut-off value for significant CAD was &gt; 182.5. ROC curve analysis for prediction of the presence of significant CAD for SPECT, CCS and the combination of CCS and SPECT resulted in an area under the curve (AUC) of 0.88 (95 % CI 81-94), 0.75 (95 % CI 66-83 %) and 0.92 (95 % CI 87-97 %) respectively. The difference of the AUC between SPECT and the combination of CCS and SPECT was 0.05 (P = 0.12). The addition of CCS did not significantly improve the diagnostic performance of SPECT in the evaluation of patients with a predominantly high pre-test likelihood of CAD

Impact of physical activity on the risk of cardiovascular disease in middle-aged and older adults: EPIC Norfolk prospective population study.

Background There is broad consensus that regular physical activity yields major health benefits. However, current guidelines on physical activity are mainly aimed at middle-aged adults. It is unclear whether physical activity also translates into cardiovascular health benefits in older adults. Therefore, we aimed to compare the association between different levels of physical activity and the risk of cardiovascular disease (CVD) in elderly to middle-aged individuals. Methods We analysed data from the EPIC Norfolk prospective population study. Cox proportional hazards models were used to analyse the association between physical activity levels and time to CVD events in three age categories (65 years). Interaction between age categories and physical activity levels was assessed. Results Analyses were based on 24,502 study participants aged 39-79 years. A total of 5240 CVD events occurred during 412,954 person-years follow-up (median follow-up was 18.0 years). Among individuals aged over 65 years, hazard ratios for CVD were 0.86 (95% confidence interval (CI) 0.78-0.96), 0.87 (95% CI 0.77-0.99) and 0.88 (95% CI 0.77-1.02) in moderately inactive, moderately active and active people, respectively, compared to inactive people. Among people aged 55-65 and less than 55 years, the associations were directionally similar, but not statistically significant. The interaction term between physical activity levels and age categories was not significant ( P = 0.38). Conclusion The inverse association between physical activity and the risk of CVD was significant in elderly and comparable with middle-aged individuals. In addition, we observed that modest levels of physical activity confer benefits in terms of CVD risk, compared to being completely inactive

C-Reactive Protein Identifies Low-Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer-Norfolk Prospective Population Study.

BACKGROUND: Conflicting data exist about the cardiovascular risk of metabolically healthy obese persons. The prognostic value of C-reactive protein (CRP) in this intriguing group is unknown. We assessed the association between CRP levels and the risk of coronary heart disease (CHD) in metabolically healthy persons with abdominal obesity. METHODS AND RESULTS: In the European Prospective Investigation of Cancer-Norfolk prospective cohort, CRP levels and information on metabolic syndrome criteria were available for 7279 participants, of whom 825 (11%) developed CHD during a follow-up period of 10.9±1.8 years. There was a trend toward a higher multivariable-adjusted hazard ratio for CHD in metabolically healthy obese participants with CRP levels >2 mg/L compared with <2 mg/L (hazard ratio 1.59, 95% CI 0.97-2.62, P=0.066). Metabolically unhealthy obese participants had significantly higher CHD risk compared with metabolically healthy obese participants with CRP levels <2 mg/L (hazard ratio 1.88, 95% CI 1.20-2.94, P=0.006). Most important, we found that the risk of CHD among metabolically healthy obese persons with CRP levels <2 mg/L was comparable to that of metabolically healthy nonobese persons (hazard ratio 0.91, 95% CI 0.60-1.39, P=0.674). CONCLUSIONS: Among metabolically healthy obese persons, low CRP levels were associated with a CHD risk comparable to that of metabolically healthy nonobese persons. CRP appears to be an easy and widely available method for identifying a low-risk subpopulation among metabolically healthy obese persons.EPIC‐Norfolk is supported by program grants from the Medical Research Council UK and Cancer Research UK. The CRP measurements in the full cohort were supported by a grant from the Medical Research Council to the Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (MRC G0701863). The funding sources had no role in the study design, the conduct of the analysis, or the decision to submit the manuscript for publication

Chocolate consumption and incident heart failure

BACKGROUND: We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association. METHODS AND RESULTS: We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993-1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58 ± 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5 ± 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100 g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66-0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71-1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (N = 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66-1.01). CONCLUSIONS: Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure.The EPIC-Norfolk study was supported by grants from the Medical Research Council and Cancer Research UK.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.numecd.2016.01.00