Epidemiological Study Of Myocardial Infarction Research Articles

Hand grip strength, anthropometrics and cognitive decline

AbstractBackgroundHand grip strength is a well validated measure of physical strength, while anthropometric measures such as weight, waist, hip and mid upper arm circumference, are well validated to determine physical health. The present analysis investigated the relationship between hand grip strength, anthropometric measures and dementia incidence in 70–90‐year‐old men residing in Northern Ireland (NI).MethodThe PRIME‐COG study is nested in PRIME (Prospective Epidemiological Study of Myocardial Infarction), a cohort study of men in NI. In the most recent follow up for PRIME‐COG, men underwent a comprehensive cognitive assessment from which a consensus diagnosis of normal cognitive function, MCI or dementia was made by experienced clinical researchers. Hand grip strength and anthropometrics measures were also recorded. Logistic regression models were performed to assess the association between hand grip strength and anthropometric measures and cognitive endpoints.ResultThe analysis identified that low hand grip strength was associated with dementia and/or MCI, although this did not reach statistical significance (OR 1.39, p = 0.18). In the anthropometric measures, a significant relationship was observed between hip circumference and dementia and/or MCI at PRIME‐COG follow up (OR 0.93, p = 0.01), whereas BMI was non‐significantly associated (OR 1.22, p = 0.58). The remaining anthropometric measures investigated were not found to hold any significant relationships with the cognitive outcomes.ConclusionWithin a cohort of older men residing in NI, low hand grip strength was associated with a 39% increased risk of dementia or MCI, although this was not statistically significant. In anthropometric measures, hip circumference was found to be significantly negatively associated with a 7% reduced risk of dementia or MCI, while BMI was associated with a 22% increased risk, which again was not of statistical significance. The present study helps further contribute to the evidence base that physical well‐being is associated with cognitive function.

Lower serum carotenoid levels are associated with incident cognitive decline independent of traditional risk factors in a prospective study of older men from Northern Ireland

AbstractBackgroundNutritional influences, and antioxidant status in particular, have been implicated in the aetiology of cognitive decline. This study investigated the neuroprotective effects of serum antioxidants in a prospective cohort of older men to identify associations with cognitive outcomes, independent of traditional risk factors.MethodThis cohort study included 873 Northern Irish men nested within PRIME (Prospective Epidemiological Study of Myocardial Infarction) who were followed‐up for at least 15 years. Mini Mental State Examination (MMSE) was carried out at baseline. The Addenbrooke’s Cognitive Examination‐R and MMSE were carried out at follow‐up. A consensus diagnosis of normal cognition for age, mild cognitive impairment (MCI) or dementia was made using accepted clinical criteria. Serum concentrations of retinol, two forms of vitamin E (α‐ and ϒ‐tocopherol) and six carotenoids measured from baseline samples were quantified by high‐performance liquid chromatography and assessed by multiple logistic regression analyses.ResultThe case definition included the 163 men characterised with MCI and 46 men with dementia; 664 participants were considered cognitively normal controls (Table 1). In unadjusted analyses, serum levels of the carotenoids α‐carotene, β‐carotene, lycopene and β‐cryptoxanthin were significantly lower in MCI/dementia cases than controls, in contrast to ϒ‐tocopherol, which was significantly higher (Table 2). Following adjustment for traditional risk factors including height, APOε4 genotype, diastolic blood pressure, smoking status and the presence of (pre)diabetes or depression, the effect size of those carotenoids significant in the unadjusted analysis was attenuated somewhat; only α‐carotene remained significantly associated with MCI/dementia (odds ratio = 0.55; confidence interval: 0.31‐0.99; Table 2).ConclusionOur data implicates lower levels of serum carotenoids as potential early biomarkers of MCI/ dementia before overt manifestation of symptoms, independent of traditional risk factors. These findings are consistent with hypotheses supportive of a neuroprotective role of dietary antioxidants and corroborate previous associations of higher serum carotenoid levels with better cognition in aging subjects. There is emerging evidence that carotenoids, through their potent antioxidant and anti‐inflammatory properties, may positively impact cognitive function. Limiting cognitive decline through lifestyle, exercise, and a higher carotenoid intake, may prove beneficial.

147 PRIME-COG study: grip strength, anthropometrics and cognitive decline

Abstract Background Measurement of hand grip strength is a validated measure of physical strength. While anthropometric measurements including waist, hip and mid-upper-arm circumference, are validated for physical health. Evidence has suggested grip strength and anthropometrics to be associated with cognitive impairment and dementia. The relationship between these variables and risk of mild cognitive impairment (MCI) or dementia was investigated in a cohort of 70–90-year-old men residing in Northern Ireland. Methods The PRIME-COG study is nested within the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study. Data collection for PRIME-COG included collection of lifestyle and demographic information. A comprehensive cognitive assessment, anthropometric measurements, and hand grip strength were measured by dementia research nurses from the Northern Ireland Clinical Research Network. Logistic regression models were performed to assess the association between hand grip strength and anthropometric measures and the composite cognitive endpoint MCI/dementia. Results Analysis identified that low hand grip strength was associated with MCI/dementia, although this did not reach statistical significance (OR 1.39, p = 0.18). Larger hip circumference was associated with reduced risk of MCI/dementia in the study population (fully adjusted model, OR 0.93, P = 0.01), while BMI was non-significantly associated with an increased risk (OR 1.22, p = 0.58). Conclusion Within the PRIME-COG cohort, low grip strength was associated with a 39% increased risk of MCI/dementia. Whilst not statistically significant, this supports the importance of grip strength as a clinical tool in the assessment of physical health in older adults. Larger hip circumference was significantly associated with a 7% reduced risk of MCI/dementia, while higher BMI was associated with a 22% increased risk, although this was not significant. Results from this study add to the evidence demonstrating the association between cognitive function and physical well-being.

The association of denture wearing with reduced lung function and increased airflow limitation in 58-72 year old men.

To investigate the association between denture wearing and airflow limitation in men in Northern Ireland enrolled in the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study. A case-control design was used to study partially dentate men. Cases were men aged 58-72 years who were confirmed as denture wearers. Controls were never denture wearers who were matched by age (± 1 month) and smoking habit to the cases. The men had a periodontal assessment and completed a questionnaire detailing their medical history, dental history and behaviours, social circumstances, demographic background and tobacco use. Physical examination and spirometry measurements of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were also undertaken. Spirometry data for edentulous men who wore complete dentures were compared with that recorded for the partially dentate men studied. There were 353 cases who were partially dentate and were confirmed denture wearers. They were matched for age and smoking habit to never denture wearer controls. The cases had an FEV1 that was on average 140 ml lower than the controls, p = 0.0013 and a 4% reduction in percent predicted FEV1, p = 0.0022. Application of the GOLD criteria indicated that 61 (17.3%) of the cases had moderate to severe airflow limitation compared with 33 (9.3%) of controls, p = 0.0051. Fully adjusted multivariable analysis showed that partially dentate men who were denture wearers were significantly more likely (p = 0.01) to have moderate to severe airflow reduction with an adjusted odds ratio (OR) of 2.37 (95% confidence intervals 1.23-4.55). In the 153 edentulous men studied moderate to severe airflow limitation was recorded in 44 (28.4%), which was significantly higher than in the partially dentate denture wearers (p = 0.017), and the men who had never worn a denture (p<0.0001). Denture wearing was associated with an increased risk of moderate to severe airflow limitation in the cohort of middle-aged Western European men studied.

211 ASSOCIATION OF PLASMA ANTIOXIDANTS AND COGNITIVE OUTCOMES IN NORTHERN IRISH MEN FROM PROSPECTIVE EPIDEMIOLOGICAL STUDY OF MYOCARDIAL INFARCTION (PRIME) STUDY

Abstract Background Oxidative stress and chronic inflammation have been demonstrated to contribute to cognitive decline in older age and the development of neurodegenerative disorders. Antioxidants have been revealed to help mitigate the effects of the damage caused by oxidative stress and inflammation, but their relationship with cognitive decline is not yet fully understood. The aim of this study was to investigate the association between various plasma antioxidant levels and cognitive status in participants from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study. Methods 10,600 men were recruited to the PRIME study between 1991-1993 and have been followed up across eleven time points. Baseline health and lifestyle characteristics were assessed, and plasma antioxidants were obtained and quantified. Baseline cognitive status was screened in 2000 using Mini-Mental State Examination (MMSE). Follow up assessment of cognitive status was performed in 2015 with MMSE and Addenbrooke’s Cognitive Examination-Revised (ACE-R) examinations. Results 2,009 men underwent cognitive assessment in 2000 and 873 men in 2015. At both 2000 and 2015 with the use of the MMSE and ACE-R examinations to assess cognitive status, serum concentration of all the antioxidants except for gamma-tocopherol and lycopene were higher in the men with better cognitive performance at a significant level of p&amp;lt;0.05. Better cognitive performance was associated with more time spent in education and higher level of education achieved at a statistically significant level (p&amp;lt;0.01). Furthermore, those with cognitive impairment were more likely to be older. After adjustments for lifestyle variables with a linear regression model, the only significant variable associated with cognition was time spent in education (B = 0.521, p= 0.02). Conclusion The findings suggest that the concentration of plasma antioxidants is associated with cognitive status. Smoking and education, as well as other lifestyle factors were, demonstrated to have an impact on cognitive status.

Association of TGFB1 rs1800469 and BCMO1 rs6564851 with coronary heart disease and IL1B rs16944 with all-cause mortality in men from the Northern Ireland PRIME study.

BackgroundHistorically, high levels of morbidity and mortality have been associated with cardiovascular disease in the Northern Ireland population. Previously reported associations between single nucleotide polymorphisms (SNPs) and cardiovascular disease within other populations have not always been consistent.ObjectiveTo investigate associations between 33 SNPs with fatal or non-fatal incident coronary heart disease (CHD) events and all-cause mortality in the Northern Irish participants of the Prospective Epidemiological Study of Myocardial Infarction (PRIME).MethodPhase 2 of the PRIME study prospectively evaluated 2,010 men aged 58–74 years in Northern Ireland for more than 10 years for incident CHD events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass, and cardiac death) and more than 15 years for all-cause mortality. SNPs previously reported in association with cardiovascular outcomes were evaluated against incident CHD events and all-cause mortality using Cox’s proportional hazards models adjusted for established cardiovascular disease risk factors.ResultsDuring the follow-up period, 177 incident CHD events were recorded, and 821 men died. Both BCMO1 rs6564851 (Hazard ratio [HR] = 0.76; 95% confidence intervals [CI]: 0.60–0.96; P = 0.02) and TGFB1 rs1800469 (HR = 1.30; CI: 1.02–1.65; P = 0.04) were significantly associated with incident CHD events in adjusted models. Only IL1B rs16944 was significantly associated with all-cause mortality (HR = 1.18; CI: 1.05–1.33; P = 0.005). No associations remained significant following Bonferonni correction for multiple testing.ConclusionWe report a novel association between BCMO1 rs6564851 and risk of incident CHD events. In addition, TGFB1 rs1800469 and IL1B rs16944 were associated with the risk of incident CHD events and all-cause mortality outcomes respectively, supporting previously reported associations.

Adherence to a Mediterranean diet is associated with better cognitive performance many years later in the PRIME cohort

AbstractBackgroundGreater adherence to a Mediterranean Diet (MD) has been associated with reduced cognitive decline and dementia risk. The Prospective Epidemiological Study of Myocardial Infarction (PRIME) recruited 10,600 European male participants between 1991 and 1993 aged 50‐59 years. The aim of this study was to examine the association between adherence to a MD (at baseline) and subsequent cognitive performance.MethodDietary data was collected via a short, self‐administered 16‐item Food Frequency Questionnaire; an adapted version of the traditional MD Score was also developed (aMDSR) and median values of intake for each MD component were used as the cut‐off point to calculate the aMDSM. In 2017, follow‐up cognitive assessments using the Addenbrooke’s Cognitive Examination – Revised (ACER) commenced within the Belfast cohort (n=405).ResultFor aMDSM, those in the Low MD category scored lower on all cognitive tests compared to the High MD category, with significant differences reported for ACE‐R (p = 0.001), ACE‐R sub domain of memory (p = 0.038), fluency (p = 0.001) and visuospatial skills (p = 0.030). For participants with a ACE‐R score below 88, suggestive of cognitive impairment, there were 19.3% in the Low MD category and 7.2% in the High MD category (p = 0.004). There were 7.4% in the Low MD category and 2.7% in the High MD category who obtained an ACE‐R score below 82, indicative of probable dementia, with no statistically significant difference between categories (p=0.09). In an adjusted model for age, education and cardiovascular risk factors, this significant difference was maintained, with those in the High MD category being 56% less likely to have an ACE‐R score of &lt;88/100 (OR 0.442, 95% CI 0.241‐0.810, p=0.008) compared to those in the Low MD category. For participants with a ACE‐R score below 82, indicative of probable dementia, there were 7.4% in the Low MD category and 2.7% in the High MD category with no statistically significant difference between categories (OR 0.661, 95%CI 0.269‐1.621, p=0.37) .ConclusionIn the PRIME Belfast cohort, higher adherence to a MD was associated with better cognitive performances 26 years later in some but not all analyses.

Association between overall fruit and vegetable intake, and fruit and vegetable sub-types and blood pressure: the PRIME study (Prospective Epidemiological Study of Myocardial Infarction).

Increased fruit and vegetable (FV) intake is associated with reduced blood pressure (BP). However, it is not clear whether the effect of FV on BP depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on BP. Baseline data from a prospective cohort study of 10 660 men aged 50-59 years examined not only the cross-sectional association between total FV intake but also specific types of FV and BP in France and Northern Ireland. BP was measured, and dietary intake assessed using FFQ. After adjusting for confounders, both systolic BP (SBP) and diastolic BP (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake; however, when examined according to fruit or vegetable sub-type (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on SBP >140 mmHg, the OR for total fruit, vegetable and fruit juice intake (per fourth) was 0·95 (95 % CI 0·91, 1·00), with the same estimates being 0·98 (95 % CI 0·94, 1·02) for citrus fruit (per fourth), 1·02 (95 % CI 0·98, 1·06) for fruit juice (per fourth), 0·93 (95 % CI 0·89, 0·98) for other fruit (per fourth), 1·05 (95 % CI 0·99, 1·10) for cooked vegetable (per fourth) and 0·86 (95 % CI 0·80, 0·91) for raw vegetable intakes (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP, DBP and risk of hypertension, but this differed by FV sub-type, suggesting that the strength of the association between FV sub-types and BP might be related to the type consumed, or to processing or cooking-related factors.

Association between oral health status and future dietary intake and diet quality in older men: The PRIME study

ObjectivesThis study investigated whether oral health status, defined as number of natural teeth and subsequent prosthodontic rehabilitation, was associated with future dietary intake and diet quality in older adults in The Prospective Epidemiological Study of Myocardial Infarction (PRIME). MethodsPRIME was originally established to explore cardiovascular risk factors in 50−59 year old men in Northern Ireland (1991–1994). A rescreening phase assessed oral health (2001–2004), while diet was assessed in 2015. Diet quality was characterised by the Dietary Diversity Score and Mediterranean Diet Score. In the current analysis, associations between oral health status, dietary intake and quality were assessed using regression models in 1096 participants. ResultsAmongst study participants, the overall mean number of teeth was 18.5, 51.5 % had ≥21 natural teeth and 49.6 % wore dentures. Oral health status was categorised into five groups: 21–28 teeth with (n = 111) and without (n = 453) dentures, 1–20 teeth with (n = 354) and without (n = 99) dentures and edentate with dentures (n = 79). After full adjustment, men with ≥21 teeth and dentures had a higher future intake of fruit, vegetables, and nuts, and diet quality scores, compared to those with <21 teeth with dentures. Edentate men with dentures were less likely to achieve the future fruit dietary recommendation. ConclusionsHaving ≥21 natural remaining teeth positively affected the future intake of fruit, vegetables, and nuts, as well as diet quality. Dentures may be beneficial in men with ≥21 natural remaining teeth, as they were associated with an increased future intake of fruit, vegetables, and nuts and better diet quality. Clinical significanceOral health status is associated with dietary intake, after an average time period of 13 years, with those with a larger number of natural teeth having a better diet quality. Further research is required to investigate this relationship in larger, diverse populations with more detailed dietary assessment.

Impact of Oral Health Status on Future Dietary Intake and Dietary Quality in Older Adults in Northern Ireland: A Longitudinal Analysis (P18-080-19)

ObjectivesEvidence linking oral health status with dietary intake and quality in older adults is inconsistent and limited by few prospective studies conducted to date. This study investigated whether oral health status, defined as number of natural teeth and prosthodontic rehabilitation, had an impact on future dietary intake and dietary quality in older Northern Irish (NI) men. MethodsThis study involved older men [n = 1096, mean = 63.5(2.9) years] from the Prospective Epidemiological Study of Myocardial Infarction (PRIME). A dental examination was undertaken at baseline (2001–2006) and oral health status was defined as: 21–28 teeth without dentures (n = 453), 21–28 teeth with dentures (n = 111), 1–20 teeth without dentures (n = 99), 1–20 teeth with dentures (n = 354), and edentate with dentures (n = 79). A food frequency questionnaire administered in 2015 derived intakes of major food groups and diet quality scores were characterised by the Dietary Diversity Score (DDS) and Mediterranean Diet Score (MDS). Associations between oral health status, food intake and diet quality scores were assessed using regression models adjusted for potential confounders including, age, socio-economic status, smoking and alcohol. ResultsIn fully adjusted models, the mean dietary intake of fruit, vegetables and nuts significantly differed between oral health status groups. In comparison to edentate men with dentures, the mean fruit intake was significantly higher in each dentate group: 21–28 teeth without dentures (P = 0.001), 21–28 teeth with dentures (P = 0.001), 1–20 teeth without dentures (P = 0.04), and 1–20 teeth with dentures (P = 0.03). The mean DDS was significantly higher amongst men with 21–28 teeth without dentures, compared to those with 1–20 teeth without dentures (P = 0.001), 1–20 teeth with dentures (P < 0.001), and edentate with dentures (P < 0.001), and mean MDS results were similar. Compared to men with 21–28 teeth without dentures, edentate men with dentures were 64% less likely to achieve the dietary guideline of 2 portions/day (P = 0.01). ConclusionsA greater number of natural teeth was associated with a higher future intake of fruit, vegetables and nuts, as well as higher dietary quality scores, in older NI men. Interventions should optimise retaining natural teeth to help improve dietary intake and quality in older adults. Funding SourcesDepartment of Economy funded PhD.

All-Cause Mortality up to and After Coronary Heart Disease and Stroke Events in European Middle-Aged Men: The PRIME Study.

The aim was to investigate prospectively the all-cause mortality risk up to and after coronary heart disease (CHD) and stroke events in European middle-aged men. The study population comprised 10 424 men 50 to 59 years of age recruited between 1991 and 1994 in France (N=7855) and Northern Ireland (N=2747) within the Prospective Epidemiological Study of Myocardial Infarction. Incident CHD and stroke events and deaths from all causes were prospectively registered during the 10-year follow-up. In Cox's proportional hazards regression analysis, CHD and stroke events during follow-up were used as time-dependent covariates. A total of 769 CHD and 132 stroke events were adjudicated, and 569 deaths up to and 66 after CHD or stroke occurred during follow-up. After adjustment for study country and cardiovascular risk factors, the hazard ratios of all-cause mortality were 1.58 (95% confidence interval 1.18-2.12) after CHD and 3.13 (95% confidence interval 1.98-4.92) after stroke. These findings support continuous efforts to promote both primary and secondary prevention of cardiovascular disease.

Depressive Symptoms, a Time-Dependent Risk Factor for Coronary Heart Disease and Stroke in Middle-Aged Men

To date, the association between depressive symptoms and the risk of cardiovascular diseases remains controversial. We investigated prospectively, within the same population, the time course of the association between baseline depressive symptoms and first stroke or coronary heart disease event. In the Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study, a multicenter, observational, prospective cohort, 9601 men from France and Northern Ireland were surveyed for the occurrence of first coronary heart disease (n=647) and stroke events (n=136) over 10 years. At baseline, the fourth quartile of a 13-item modified Center for Epidemiological Studies questionnaire was used to define the presence of depressive symptoms. We sought the best time-dependent function to assess the association between depressive symptoms and outcomes. Thus, the hazard ratios were estimated by a Cox proportional hazard model after splitting the follow-up before and after 5 years of follow-up time periods. Depressive symptoms at baseline were associated with coronary heart disease in the first 5 years of follow-up (hazard ratio, 1.43; 1.10-1.87) and with stroke in the second 5 years of follow up (hazard ratio, 1.96; 1.21-3.19) after adjustment for age, study centers, baseline socioeconomic factors, traditional vascular risk factors, and antidepressant treatment. The association was even stronger for ischemic stroke (n=108; hazard ratio, 2.48; 1.45-4.25). The current study suggests that in healthy, European, middle-aged men, baseline depressive symptoms are associated with an increased risk of coronary heart disease in the short-term, and for stroke in the long-term.

Plasma Biomarkers for Prediction of Sudden Cardiac Death

Sudden cardiac death (SCD) accounts for most cardiovascular deaths in the United States, claiming an estimated 300 000 lives per year.1 Despite intense efforts to develop resuscitation techniques, survival rates are still low, at ≈5%.2 This has led to a renewed focus in this field directed toward optimizing risk prediction to identify the candidate that would qualify for prophylactic or preventive interventions.3 At present, the clinical risk stratification is largely limited to the use of left ventricular ejection fraction (LVEF) for identifying primary prophylaxis candidates, but specificity of this predictor is modest.4 Moreover, the absolute numbers of these high-risk patients in the general population are low. Instead, the highest prevalence of SCD is likely observed among previously asymptomatic individuals, even though it is well-known that coronary artery disease (CAD) is present in most SCD cases.5 This underscores the need for the development of risk stratification models that can be applied to the general population where the largest health benefit is likely to be realized. The underpinnings of SCD are complex, and it is reasonable to believe that the risk stratification instrument of the future is likely to involve other components beyond clinical risk markers. Novel genomic variants show promise but are still in early phases of development as risk stratification targets. However, the “unbiased” approaches made possible through genomewide association studies have led to the recent identification of specific genetic variants that could predict SCD.6,7 This has reignited the interest in plasma biomarkers as a means for risk stratification. This article will review the emerging evidence and role of plasma biomarkers in predicting SCD in the general population and suggest a blueprint for future studies of potential utility. ### Uniform Definition of SCD Given the complexity and dynamic nature of the condition, there has been some variability …

Could clinical decision rules relying on cardiovascular risk models increase psychosocial inequalities in health? Results from the PRIME cohort study

Objective Guidelines on cardiovascular prevention relying on common cardiovascular risk scoring could result in delayed drug therapy for patients with low psychosocial status because of underestimation of true cardiovascular risk. We aimed to assess the potential delay in drug therapy for subjects with adverse psychosocial factors. Method The study population consisted of 6185 French men from the PRIME (Prospective Epidemiological Study of Myocardial Infarction) cohort study (1991–2003). The number of extra years to reach a risk threshold for subjects without adverse psychosocial factor compared to subject with adverse psychosocial factor was estimated using a coronary risk model including biomedical factors and a psychosocial variable (education, occupation, living conditions or a depression score). Results Coronary risk was significantly higher only for subjects with a high depression score (odds ratio = 1.34; 95% confidence interval 1.04, 1.72) or low educational attainment (odds ratio = 1.39; 95% confidence interval = 1.07, 1.81). For a given risk threshold, subjects with high depression scores were 4.5 years (95% confidence interval = 0.0, 15.4 years) younger than subjects with low depression scores. The age difference was 4.1 years (95% confidence interval = − 0.5, 15.8 years) between subjects with low and high educational attainment. Conclusion Clinical decision rules relying on classic cardiovascular risk scoring could result in delayed drug therapy for patients with depression or low educational attainment.

Relative Contribution of Lipids and Apolipoproteins to Incident Coronary Heart Disease and Ischemic Stroke: The PRIME Study

Aim: To compare within the same cohort the association of a large panel of lipids with the risk of incident coronary heart disease (CHD) and ischemic stroke events in participants of the Prospective Epidemiological Study of Myocardial Infarction. Methods: In this binational (Northern Ireland and France) prospective cohort, we considered 9,711 men aged 50–59 years free of CHD and stroke at baseline (1991–1993). The hazard ratios of each lipid marker for CHD and ischemic stroke events were estimated in separate Cox proportional hazard models adjusted for age, study center, systolic blood pressure, antihypertensive treatment, current smoking status, body mass index and diabetes. Results: After 10 years of follow-up, 635 men had a first CHD and 98 a first ischemic stroke event. Total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, triglycerides, apolipoprotein (Apo) A1 and Apo B100, their ratios and lipoprotein (a) [Lp(a)] were all significantly predictive of future CHD. Associations with ischemic stroke followed the same trend as for CHD, but with lower strength, and none were statistically significant. However, none of the differences between the hazard ratios for CHD and for ischemic stroke were statistically significant. Conclusions: In healthy, middle-aged men, total-C, HDL-C, LDL-C, non-HDL-C, triglycerides, Apo A1 and Apo B100, their ratios and Lp(a) are, if anything, weak predictors of ischemic stroke events over a 10-year period.

Contribution of 30 Biomarkers to 10-Year Cardiovascular Risk Estimation in 2 Population Cohorts

Cardiovascular risk estimation by novel biomarkers needs assessment in disease-free population cohorts, followed up for incident cardiovascular events, assaying the serum and plasma archived at baseline. We report results from 2 cohorts in such a continuing study. Thirty novel biomarkers from different pathophysiological pathways were evaluated in 7915 men and women of the FINRISK97 population cohort with 538 incident cardiovascular events at 10 years (fatal or nonfatal coronary or stroke events), from which a biomarker score was developed and then validated in the 2551 men of the Belfast Prospective Epidemiological Study of Myocardial Infarction (PRIME) cohort (260 events). No single biomarker consistently improved risk estimation in FINRISK97 men and FINRISK97 women and the Belfast PRIME Men cohort after allowing for confounding factors; however, the strongest associations (with hazard ratio per SD in FINRISK97 men) were found for N-terminal pro-brain natriuretic peptide (1.23), C-reactive protein (1.23), B-type natriuretic peptide (1.19), and sensitive troponin I (1.18). A biomarker score was developed from the FINRISK97 cohort with the use of regression coefficients and lasso methods, with selection of troponin I, C-reactive protein, and N-terminal pro-brain natriuretic peptide. Adding this score to a conventional risk factor model in the Belfast PRIME Men cohort validated it by improved c-statistics (P=0.004) and integrated discrimination (P<0.0001) and led to significant reclassification of individuals into risk categories (P=0.0008). The addition of a biomarker score including N-terminal pro-brain natriuretic peptide, C-reactive protein, and sensitive troponin I to a conventional risk model improved 10-year risk estimation for cardiovascular events in 2 middle-aged European populations. Further validation is needed in other populations and age groups.

Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial Infarction (PRIME)

Objective To investigate the effect of alcohol intake patterns on ischaemic heart disease in two countries with contrasting lifestyles, Northern Ireland and France.Design Cohort data from the Prospective Epidemiological Study...

Respective contribution of conventional risk factors and antihypertensive treatment to stable angina pectoris and acute coronary syndrome as the first presentation of coronary heart disease: the PRIME Study

To test whether conventional risk factors and antihypertensive treatment were more predictive of stable angina (SA) than acute coronary syndrome (ACS) as the first presentation of coronary heart disease (CHD). We used data from the PRIME Study (Prospective Epidemiological Study of Myocardial Infarction), a prospective cohort of 9758 asymptomatic middle-aged men recruited from WHO MONICA centers in Northern Ireland and France between 1991 and 1993. SA and ACS events were registered during 5 years of follow-up. Hazard ratios (HRs) of each risk factor measured at baseline for SA and ACS events were assessed using separate Cox proportional hazard models. Difference between HRs was estimated by the bootstrap method. After 5 years of follow-up, there were 114 SA and 178 ACS as the first presentation of CHD. Diastolic blood pressure [adjusted HRs for 1 standard deviation increase = 1.34; 95% confidence interval (CI): 1.17-1.54 vs. 1.04; 95% CI: 0.87-1.25; P for comparison between HRs = 0.012], and possibly cigarette smoking over or equal to 20 pack-years (adjusted HR = 2.07; 95% CI: 1.43-2.99 vs. 1.29; 95% CI: 0.83-2.01; P for comparison between HRs = 0.062) were more predictive of ACS than SA, whereas this was the opposite for antihypertensive treatment (adjusted HR = 2.18; 95% CI: 1.39-3.41 for SA vs. 1.28; 95% CI: 0.85-1.93 for ACS, P for comparison between HRs = 0.049). The present data support that SA and ACS, as the first presentation of CHD, may not share exactly the same determinants.

Residual cardiovascular risk in treated hypertension and hyperlipidaemia: the PRIME Study

Although pharmacological treatments of hypertension and dyslipidaemia are both associated with a reduction in cardiovascular risk, little is known about the degree of cardiovascular risk remaining in treated individuals, by assessing the levels of their risk factors achieved, that is their 'residual cardiovascular risk'. We then used the data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME), which involved 9649 men aged 50-59 years, from France and Northern Ireland with a 10-year follow-up, to test the presence of specific residual cardiovascular risks of coronary heart disease, stroke, total of fatal and non-fatal cardiovascular events and cardiovascular mortality, in patients treated with antihypertensive agents or lipid-lowering agents. In the whole cohort, a total of 796 patients developed a fatal or non-fatal cardiovascular event. Antihypertensive drug use at baseline was significantly associated (RR=1.50, 95% CI: 1.25-1.80) with total cardiovascular event risk, but not lipid-lowering drug use, after adjusting for classic risk factors (age, smoking, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure and diabetes). Similar results were obtained for coronary heart disease (RR=1.46, 95% CI: 1.18-1.80), stroke (RR=1.75, 95% CI: 1.14-2.70) and cardiovascular death (RR=1.62, 95% CI: 1.02-2.58), but neither for total death (RR=1.15, 95% CI: 0.89-1.48) nor for non-cardiovascular death (RR=1.00, 95% CI: 0.74-1.36). For any cardiovascular end point, residual risks did not globally differ according to the antihypertensive drug class prescribed at baseline. In conclusion, treatment with antihypertensive agents, but not with lipid-lowering agents, was associated with a sizeable residual cardiovascular risk, suggesting that more efficient risk reduction strategies in hypertension should be developed as a priority.

Influence of cholesteryl ester transfer protein, peroxisome proliferator–activated receptor α, apolipoprotein E, and apolipoprotein A-I polymorphisms on high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I:A-II concentrations: the Prospective Epidemiological Study of Myocardial Infarction study

The plasma level of high-density lipoprotein cholesterol (HDL-C) is known to be inversely associated with cardiovascular risk. However, besides lifestyle, gene polymorphism may influence the HDL-C concentration. The aim of this study was to investigate the possibility of interactions between CETP, PPARA, APOE, and APOAI polymorphisms and HDL-C, apolipoprotein (apo) A-I, lipoprotein (Lp) A-I, and Lp A-I:A-II in a sample selected from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study population who remained free of cardiovascular events over 5 years of follow-up. Healthy individuals (857) were randomly selected for genotyping the PRIME study subjects. The population was selected so as to provide 25% of subjects in the lowest tertile of HDL-C (≤28 mg/dL) in the whole PRIME study sample, 25% of subjects in the highest tertile of HDL-C (≥73 mg/dL), and 50% of subjects in the medium tertile of HDL-C (28-73 mg/dL). Genotyping was performed by using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assay. The CETP A373P rare allele c was less frequent in the group of subjects with high HDL-C, apo A-I, Lp A-I, and Lp A-I:A-II concentrations. Apolipoprotein A-I and Lp A-I were also found to be higher in the presence of the ɛ2 allele coding for APOE. The effect of the CETP A373P rare allele c on HDL-C was independent of all tested parameters except triglycerides. The respective effect of these polymorphisms and triglycerides on cardiovascular risk should be evaluated prospectively.