High CHD Risk Research Articles

Impact of coronary calcium on arterial age and coronary heart disease risk estimation using the MESA arterial age calculator

Background We evaluated the impact of arterial age calculation on reclassification of global coronary heart disease risk using the Framingham risk score. Methods We applied CHD risk factor data from the Prospective Army Coronary Calcium Project to the MESA arterial age calculator (available at http://www.mesa-nhlbi.org). Subjects ( N = 1998) were studied with measured CHD risk factors and electron beam computed tomography for the identification of coronary artery calcium. Framingham risk scores (FRS), using the 10-year CHD risk model with and without arterial age, were calculated using the MESA arterial age calculator. Results The mean FRS of the cohort (42.9 ± 2.7 years, male gender 82%) was 4.5 ± 3.6%. Coronary calcium was present in 394 subjects (19.7%). Application of the arterial age calculator increased mean age from 42.9 ± 2.7 to 43.6 ± 10.4 years ( P < .001), and the mean FRS increased from 4.5 ± 3.6 to 7.3 ± 8.1% ( P < .001). Reclassification was seen primarily among male subjects, in whom the mean age (chronological vs. arterial age) increased from 42.9 ± 2.7 to 44.2 ± 11.0 ( P < .001) and the prevalence of high CHD risk increased from 0.6% (10 of 1639) to 10% (165 of 1639; P < .001). Conclusion Among healthy individuals ages 40–50, application of the MESA arterial age calculator reclassifies 1 in 10 men from low to intermediate risk and 1 in 15 men from low to high risk.

Ezetimibe added to atorvastatin compared with doubling the atorvastatin dose in patients at high risk for coronary heart disease with diabetes mellitus, metabolic syndrome or neither

Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are both associated with increased risk for atherosclerotic coronary heart disease (CHD). Thus, it is useful to know the relative efficacy of lipid-altering drugs in these patient populations. A double-blind, parallel group trial of adult patients with hypercholesterolaemia at high-CHD risk receiving atorvastatin 40 mg/day compared atorvastatin 40 mg plus ezetimibe 10 mg (ezetimibe) vs. doubling atorvastatin to 80 mg. This post hoc analysis reports lipid efficacy results in patients grouped by diagnosis of T2DM, MetS without T2DM or neither. Per cent change from baseline at week 6 was assessed for LDL-C, total cholesterol, HDL-C , non-HDL-C , Apo A-I, Apo B and triglycerides. Safety was monitored through clinical and laboratory adverse events (AEs). Compared with doubling atorvastatin, atorvastatin plus ezetimibe resulted in greater reductions in LDL-C, triglycerides, Apo B, non-HDL-C, total cholesterol and lipid ratios in the T2DM, MetS and neither groups. Treatment effects were of similar magnitude across patient groups with both treatments, except triglycerides, which were slightly greater in the T2DM and MetS groups vs. neither group. Changes in HDL-C , Apo A-I and high sensitivity C-reactive protein (hs-CRP) were comparable for both treatments in all three groups. Safety and tolerability profiles were generally similar between treatments and across patient groups, as were the incidence of liver and muscle AEs. Compared with doubling atorvastatin to 80 mg, addition of ezetimibe to atorvastatin 40 mg produced greater improvements in multiple lipid parameters in high-CHD risk patients with T2DM, MetS or neither, consistent with the significantly greater changes observed in the full study cohort (clinical trial # NCT00276484).

Predictors of ischemic cardiovascular disease in middle-age Chinese with optimal low-density lipoprotein cholesterol

Objectives To identify the risk factors of CHD and ischemic stroke in participants with optimal LDL-C compared with higher LDL-C. Design and methods In the Chinese Multi-provincial Cohort Study, 30,378 participants aged 35 to 64 and free of CVD were recruited from 11 provinces in China and followed up for 12 years. The risk factors of CHD and ischemic stroke were identified for participants with optimal (<100 mg/dl) LDL-C compared with higher LDL-C. Results Mean level of LDL-C was 106.7 mg/dl (±41.6) at baseline. Thirty-four percent of the ICVD events occurred from participants with optimal LDL-C. After adjusting for age and baseline LDL-C, central obesity and elevated triglycerides significantly predicted the incidence of CHD in participants with optimal LDL-C, but not in those with higher LDL-C. In contrast, diabetes, smoking, and male gender were significantly associated with CHD incidence in higher but not in the optimal LDL-C group. Hypertension was associated with a higher CHD risk in whole LDL-C spectrum, whereas low HDL-C was not associated with CHD in either LDL-C level independent of other risk factors. Similarly, central obesity was a significant risk factor of ischemic stroke in optimal but not in higher LDL-C group, while diabetes, smoking and male gender were risk factors of ischemic stroke in higher but not in optimal LDL-C group. Hypertension and low HDL-C were, but elevated triglycerides were not, significant predictors of ischemic stroke regardless of LDL-C level. Conclusions In this cohort, about 1/3 of the ICVD events occurred in participants with optimal LDL-C, so the intervention of other risk factors must be emphasized in this population. Intensive control of central obesity and elevated triglycerides would be especially important to further reduce the risk of ICVD in people with low LDL-C, whereas the management of diabetes and smoking merits enforcement in hypercholesterolemia patients. Objectives To identify the risk factors of CHD and ischemic stroke in participants with optimal LDL-C compared with higher LDL-C. Design and methods In the Chinese Multi-provincial Cohort Study, 30,378 participants aged 35 to 64 and free of CVD were recruited from 11 provinces in China and followed up for 12 years. The risk factors of CHD and ischemic stroke were identified for participants with optimal (<100 mg/dl) LDL-C compared with higher LDL-C. Results Mean level of LDL-C was 106.7 mg/dl (±41.6) at baseline. Thirty-four percent of the ICVD events occurred from participants with optimal LDL-C. After adjusting for age and baseline LDL-C, central obesity and elevated triglycerides significantly predicted the incidence of CHD in participants with optimal LDL-C, but not in those with higher LDL-C. In contrast, diabetes, smoking, and male gender were significantly associated with CHD incidence in higher but not in the optimal LDL-C group. Hypertension was associated with a higher CHD risk in whole LDL-C spectrum, whereas low HDL-C was not associated with CHD in either LDL-C level independent of other risk factors. Similarly, central obesity was a significant risk factor of ischemic stroke in optimal but not in higher LDL-C group, while diabetes, smoking and male gender were risk factors of ischemic stroke in higher but not in optimal LDL-C group. Hypertension and low HDL-C were, but elevated triglycerides were not, significant predictors of ischemic stroke regardless of LDL-C level. Conclusions In this cohort, about 1/3 of the ICVD events occurred in participants with optimal LDL-C, so the intervention of other risk factors must be emphasized in this population. Intensive control of central obesity and elevated triglycerides would be especially important to further reduce the risk of ICVD in people with low LDL-C, whereas the management of diabetes and smoking merits enforcement in hypercholesterolemia patients.

Socioeconomic differences in statin use after deregulation of simvastatin in the UK: the Whitehall II prospective cohort study

To examine socioeconomic differences in statin use after deregulation of simvastatin in adults with moderate or high risk of coronary heart disease. Prospective cohort study. 20 civil service departments in...

The effect of dairy foods on CHD: a systematic review of prospective cohort studies

There is interest in the degree to which fats in dairy foods contribute to CHD. We undertook a systematic review to investigate the effect of dairy consumption on CHD using prospective cohort studies. A systematic search of electronic databases identified studies relating dairy food intake in adulthood to episodes or death from CHD, IHD and myocardial infarction. Included studies were assessed for quality based on study methodology, validity of dietary assessment, success of follow-up, standardised assessment of CHD, IHD or myocardial infarction end points and appropriateness of statistical adjustment. Data from twelve cohorts involving >280,000 subjects were included. Most studies had follow-up of >80 %, adjusted statistically for three or more confounders and used standard criteria to determine end points. About half the studies used a validated FFQ, administered the FFQ more than once or had follow-up of >20 years. Fewer than half the studies involved subjects representative of the general population. Four of the twelve cohorts found no association between dairy intake and CHD. Eight studies reported varying relationships between different dairy foods and CHD or differential associations based on race, sex or over time. Although dairy foods contribute to the SFA composition of the diet, this systematic review could find no consistent evidence that dairy food consumption is associated with a higher risk of CHD. This could be due to the limited sensitivity of the dietary assessment methods to detect an effect of a single food in a mixed diet on complex clinical outcomes.

A composite scoring of genotypes discriminates coronary heart disease risk beyond conventional risk factors in the Boston Puerto Rican Health Study

Background and aims Using a genetic predisposition score (GPS), integrating the additive associations of a set of single nucleotide polymorphisms (SNPs) with CHD, we examined the consequences of the joint presence of a high GPS and conventional risk factors (CRFs). Methods and results We studied 11 SNPs at eight loci in 197 participants with prior CHD and 524 CHD-free subjects from the Boston Puerto Rican Health Study. Each polymorphism contributed 1 unit (high-risk allele homozygous), 0.5 units (heterozygous) and 0 units (low-risk allele homozygous) to the GPS. Odds ratio (OR) of CHD for those at high risk because of GPS (>5) and simultaneous presence of CRFs were estimated, compared with subjects at low risk, for both measurements. The mean score was higher in participants with prior CHD than those CHD-free ( P = 0.015), and the OR for CHD with a GPS > 5 was 2.90 ( P < 0.001).The joint presence of a high GPS and each CRF was associated with higher risk of CHD. Compared to participants with high GPS, those with low GPS (≤5) were protected against CHD even if they were smokers (OR = 0.44), heavy drinkers (OR = 0.43), displayed low physical activity (OR = 0.35), had hypertension (OR = 0.52) or hyperlipidemia (OR = 0.34) ( P values ranging from 0.004 to 0.023). Conclusion A simple genetic score of 11 polymorphisms may identify those subjects at increased risk of CHD beyond conventional risk factors.

A cross-sectional study of QOL of diabetic patients at tertiary care hospitals in Delhi

Background:According to WHO estimates India will be the global capital of diabetes by 2025, accounting for 57.2 million diabetics. Worsening the situation is the fact that diabetes affects the economically productive age-group (45-65 years) in developing countries.Objective:To measure quality of life (QOL) and study the clinical profiles and associated sociodemographic factors affecting diabetic patients aged 20 years and above.Materials and Methods:We conducted a hospital-based cross-sectional study using a generic instrument, Short-Form 36 (SF-36 of the Medical Outcome Study Group) to measure QOL of diabetic subjects aged ≥20 years. Two hundred and sixty diabetics, including 91 males and 169 females, were selected from the clinics of SSK Hospital and Dr RML Hospital of New Delhi. Data was analysed using SPSS for Windows, version 12.Results:The mean age of the respondents was 49.7 years, with 80% of respondents being in the age-group of 40-69 years. The majority (52.1%) of female respondents were illiterate and 91.1% were economically dependent. Of the male respondents, 65.9% were skilled workers. Substance abuse was present among 41.8% male subjects. Type 2 diabetes was the commonest, with 94.6% of the subjects having this form. The mean duration of diabetes was 6.96 ± 6.08 years. Oral hypoglycemic agents were being taken by 70.77% of the respondents. Among the diabetics the most common comorbidity was hypertension (30.8%) and the commonest complication was neuropathy (26.2%). We calculated the body mass index (BMI) of all subjects and found that, 46.2% of the male and 59.8% of the female respondents were either overweight or obese. As predicted by the waist/hip ratio (WHR), 53.8% of the male and 66.9% of the female respondents had high risk for CHD. Regular physical activity was undertaken by less than half of the subjects (46.5%). Out of eight domains of QOL in the SF-36, the two most affected were ‘General Health’ and ‘Vitality.’ Overall, males had higher QOL scores; this was found to be statistically significant (P = 0.0001). SF-36 and its eight domain scores had significant association with socioeconomic status, education, and habitual physical activity.Conclusion:Diabetes had an adverse effect on the QOL of these study subjects. Females had a significantly poorer QOL than males. The domains most affected were ‘General Health’ and ‘Vitality.’ Poor scores in the QOL domains were significantly associated with lower socioeconomic status, lesser education, and lesser habitual physical activity.

C-Reactive Proteins and Cardiovascular Risk Indices in Hypertensive Nigerians.

C-reactive protein (CRP), a biomarker of inflammation, has been found to play a role in the pathogenesis of cardiovascular disease and its determination has been proposed as one method of improving the prediction of the risk of cardiovascular events. CRP was determined in 150 hypertensive patients aged 30-59 years and 30 apparently healthy normotensive individuals matched for age and socioeconomic status by ELISA technique. Atherogenic index (LDL-C/HDL-C) and coronary heart disease risk (HDL-C/TC) were also calculated from the lipid profile. Among the hypertensive patients, only 1 (1.2%) female had a dangerous coronary heart disease risk, while 14 (9.3%) (6 males and 8 females) were at high risk of CHD and only 16 (10.7%) (11 males and 5 females) had probable protection against CHD. Hypertensive patients were significantly (p < 0.05) heavier than the normotensive patients (28.34 ± 4.40kg/m vs. 25.79 ± 2.91kg/m), with significantly higher atherogenic indices and CRP. Among the hypertensive patients, CRP positively correlated with atherogenic index (r = 0.551, p < 0.05) and CHD risk (r = 0.589, p < 0.05). However, in normotensive patients, CRP was positively correlated with atherogenic index (r = 0.492, p < 0.01) but negatively correlated with CHD risk (r = -0.475, p < 0.01). In conclusion, hypertensive Nigerians have significantly higher CRP than their normotensive counterparts, which correlates with CHD risk.

Abstract 5051: Alteration of Atherogenic Lipoproteins by Statin Therapy in Patients With Diabetes in a Large Pooled Clinical Trial Database

Reducing LDL-C to current goals may still leave an excess of atherogenic lipoproteins as reflected in apolipoprotein (Apo) B levels. Apo B provides a measure of atherogenic particles in blood, a predictor of CHD events. Patients with diabetes mellitus (DM) are at increased CHD risk and warrant intensive therapy. Recent joint ADA and ACCF guidelines recommend reducing Apo B to &lt;90 mg/dL in high-risk patients and optionally to &lt;80 mg/dL in those at very high risk. We examined the effect of statin therapy on the relationship between these Apo B targets and LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) in high-risk patients with and without DM. A pooled analysis of data in the rosuvastatin clinical development program was used to identify 12,269 high CHD risk patients who were examined at baseline and after therapy with rosuvastatin, atorvastatin or simvastatin. Apo B was compared with LDL-C and non-HDL-C both at baseline and on therapy using linear regression. At baseline, Apo B target of 90 mg/dL in DM was equivalent to LDL-C of 115 mg/dL and non-HDL-C of 139.8 mg/dL, which was slightly higher than for non-DM (Table ). Achieving Apo B of 90 mg/dL or 80 mg/dL required much more aggressive LDL-C and non-HDL-C goals on statin therapy. Of note, this effect and resultant targets were very similar in DM and non-DM. Achieving with statin therapy Apo B of 90 mg/dL in high-risk patients requires LDL-C target of ~80 mg/dL and non-HDL-C target of ~108 mg/dL. The on-therapy LDL-C target (&lt;70 mg/dL) and non-HDL-C target (&lt;100 mg/dL) for very high risk patients correspond to Apo B target of 80 mg/dL. During statin therapy, Apo B correlated well with LDL-C (R 2 =0.77– 0.81) and very well with non-HDL-C (R 2 =0.88 – 0.90). Non-HDL-C may be a useful surrogate for direct Apo B measurement. High-risk DM and non-DM patients require lower LDL-C and non-HDL-C targets during statin therapy in order to reduce Apo B to the recommended level.

Abstract 5147: A Cluster Randomised Controlled Trial to Evaluate an Ambulatory Primary Care Management Program for Patients with Dyslipidemia: TEAM Study

Dyslipidemia management in primary care is often sub-optimal. New Quebec (Canada) legislation increases the potential for family physician-community pharmacist collaborative care (PPCC). We hypothesized that PPCC can improve the management of dyslipidemia. In a randomized controlled trial, clusters of physicians and pharmacists within the same geographical area were randomly assigned to the PPCC or the usual care (UC) group. PPCC pharmacists attended a one-day workshop and successfully completed a clinical skills evaluation. In the PPCC intervention, the physicians are responsible for the diagnosis and the prescription of lipid-lowering pharmacotherapy, while the pharmacists initiate treatment; request appropriate laboratory tests; monitor effectiveness, safety, and adherence to treatment; and adjust medication dosage accordingly. In PPCC, physician-pharmacist communication procedures were pre defined to enhance professional collaboration. Moderate and high CHD risk patients initiating statin treatment or currently on treatment but inadequately controlled were recruited and followed-up for 1 year. The primary endpoint was the mean change difference in LDL between groups after 1 year. Secondary endpoints included the proportion of patients at or below their target LDL and TC/HDL ratio, as defined by the Canadian Lipid Guidelines, after 1 year. Multilevel and multivariate regression models were used. We enrolled 15 clusters of physicians and pharmacists (PPCC: 108 patients; UC: 117 patients). The mean change in LDL after 1 year was -1.11 mmol/L (95%CI: −1.26 to −0.96) and −0.89 mmol/L (−0.95 to −0.83) in PPCC and UC groups, respectively. The adjusted mean change difference in LDL between PPCC and UC groups was −0.11 mmol/L (−0.34 to 0.11). After 1 year, 80.6% of PPCC patients and 72.9% of UC patients were at or below their target lipid levels (adjusted OR 2.1; 1.2 to 3.8; p=0.008). PPCC patients had more lipid-lowering pharmacotherapy changes (OR: 2.0; 1.1 to 3.8) and were more likely to report lifestyle changes (OR: 3.9; 2.4 to 6.3). Our data shows that the Family physician-community pharmacist collaborative care improves the adherence to the Canadian Lipid Guidelines.( ISRCTN66345533 )

398: Walnut-enriched meat consumption improves the thrombogenic status in individuals at high CHD risk. A cross-over, placebo-controlled study

398: Walnut-enriched meat consumption improves the thrombogenic status in individuals at high CHD risk. A cross-over, placebo-controlled study

Out of hospital sudden cardiac death in Italy: a population-based case–control study

Sudden cardiac death (SCD) is a major cause of death in western countries, with coronary heart disease (CHD) being the basis of over 70% of SCD. Incidence in high-CHD risk countries has already been studied, but this information is not available for Mediterranean low-CHD risk countries. Incidence is of paramount importance when cost-effectiveness rate of actions against SCD must be estimated. We estimated the incidence of SCD and its potential risk associated with clinical variables, by a means of a case-control study in a general practice setting. The enrolled general practitioners (GPs) provided data about the total number of their patients, and identified all their patients who suffered an out-of-hospital SCD during the previous 365 days. Two age-matched and gender-matched controls visiting GPs office after the SCD selection were also selected. We used a structured questionnaire to obtain information about potential risk factors for SCD. Covariates that were univariately associated with SCD were included in the multivariate regression analyses. In a population of 297 340 (age greater than 14 years), a total of 230 cases were identified (0.77 per 1000 individuals), mostly occurring at home and among persons with known high cardiovascular risk. In the multivariate analysis only CHD (OR: 1.67; 95% CI: 1.09-2.58), arrhythmia (OR: 2.2; 95% CI: 1.3-3.9), obesity (OR: 2.3; 95% CI: 1.5-3.6), alcohol abuse (OR: 1.8; 95% CI: 1.2-2.7), and family history of CHD (OR 3.1; 95% CI: 1.8-5.3) resulted in a significant association with SCD. The incidence of SCD in Italy is lower than that reported in high-CHD risk population, most of the cases occurring at home and among persons with known high cardiovascular risk. Implementing recommendations for these patients seems to be the most effective strategy to reduce the incidence of SCD.

Role of apolipoproteins E and A-I: Epistatic villains of triglyceride mediation in coronary heart disease

The epistatic effects of ApoE (HhaI) and ApoA-I (PstI) genes as the genetic modulators of lipid levels were investigated in 165 angiographically verified CHD patients and 120 controls of Punjab, a northwest province of India. It has been revealed that of all the genotypic combinations of ApoE and ApoA-I, E4 allele carriers (E4+) with P1P2 genotype (ApoA-I/PstI) had higher risk of CHD (OR 2.99, CI 1.31–6.8, P < 0.01) which exacerbated (OR 3.44, CI 1.45–8.15, P < 0.01) after adjustment with the confounders. Individually, neither ApoA-I nor ApoE was found to be associated with TG levels however, pairwise epistasis (additive × additive model) explored their significant synergistic contributions with raised TG levels ( P < 0.01).

Prevalence and predictors of lipid abnormalities in patients treated with statins in the UK general practice

Objective To identify the prevalence and predictors of lipid abnormalities in statin-treated patients in the UK. Methods A retrospective cohort study was performed using the UK General Practice Research Database. Patients ≥35 years of age were included if they received first-ever statin between January 2000 and December 2004, received statins for at least 6 weeks, had >2 years of pre- and 1 year of post-statin initiation database history, received no concomitant lipid lowering drugs and had at least one complete lipid profile conducted within 1 year before and after initiating statins. Predictors of each lipid abnormality were determined using random effects logistic regression. Results Within 1 year of statin initiation, 34.7%, 27.4%, 68.2% and 57.6% of patients did not reach optimal levels of TC, LDL-C, HDL-C and TG, respectively. Failure to attain TC goal was explained by smoking (odds ratio = 1.13, 95% confidence interval [1.02–1.23]) and baseline TC >6.2 mmol/L (5.01, [4.58–5.48]). Failure to attain LDL-C goal was associated with smoking (1.28, [1.14–1.43]), LDL-C ≥4.1 to <4.9 mmol/L (2.72, [2.45–3.03]) and LDL-C ≥4.9 mmol/L (8.54, [7.62–9.54]). High CHD risk was associated with low HDL-C in women at follow-up (1.94, [1.51–2.48]). Elevated TG was associated with baseline TG ≥2.2 to <5.6 mmol/L (4.19, [3.81–4.59]), TG ≥5.6 mmol/L (16.10, [3.67–70.57]), smoking (1.26, [1.11–1.42]) and hypertension (1.12, [1.01–1.23]). Conclusion While TC and LDL-C management appear appropriate in the UK, attainment of recommended levels of HDL-C and TG remains poor. The latter remains a concern, as poor attainment of recommended levels of HDL-C and TG is associated with high CHD risk in women, smoking and hypertension.

Effectiveness of rosuvastatin in low-density lipoprotein cholesterol lowering and National Cholesterol Education Program Adult Treatment Panel guideline III LDL‑C goal attainment compared to other statins among diabetes mellitus patients: a retrospective study using an electronic medical records dataset in the United States

ABSTRACTObjective: To compare effectiveness of rosuvastatin (RSV) with other statins on lowering low-density lipoprotein cholesterol (LDL-C) and LDL‑C goal attainment among patients with type 1 or type 2 diabetes mellitus.Methods: A retrospective study using US General Electric Medical Systems (GEMS) database of patients with diabetes mellitus (ICD9 code = 250, prescription for anti-diabetic medication or fasting blood glucose level ≥ 126 mg/dL in the 12 months preceding statin therapy) treated across clinical practices in the US, who were newly prescribed statin therapy during August 2003 – March 2006, was conducted. Multivariate linear and logistic regression models were used for analyzing prescription data with baseline LDL-C, age, gender, smoking, very high CHD risk, systolic blood pressure, and statin duration as covariates.Results: Of 4754 diabetes mellitus patients, 5% were prescribed RSV, 59% atorvastatin (ATV), 21% simvastatin (SMV), 5% pravastatin (PRV), 2% fluvastatin (FLV), and 7% lovastatin (LOV). RSV patients had significantly higher ( p < 0.05) baseline mean LDL‑C levels (138 vs. 117–131 mg/dL), lower average starting dose (11.7 vs. 17.0–63.7 mg) and were younger ( p < 0.005) than patients on other statins (mean age 61 vs. 63–69 years). Percent LDL‑C reduction was significantly greater ( p < 0.0001) with RSV (28.4%) compared to ATV (22.5%), SMV (20.1%), PRV (13.7%), FLV (15.8%), and LOV (17.3%). A greater ( p < 0.05) proportion of RSV diabetes patients attained LDL‑C goal < 100 mg/dL (72.8%) vs. diabetes mellitus patients on other statins (36.8–67.4%).Conclusions: Rosuvastatin was more effective in lowering LDL‑C and achieving LDL‑C treatment goals in the diabetes mellitus population as compared to other statins in real-world clinical practice setting. Validating study results in a different diabetes population with dispensed statin prescriptions will help increase generalizability of study findings.

Morphological Changes in Young Adult Males Over a 40 Year Period; The Loughborough University Alumni Study.

Longitudinal studies on ageing are not common amongst the literature due to the inherent difficulties involved in long term data collection. PURPOSE: To describe the morphological changes; Body Mass Index (BMI), percentage Body Fat (%BF) and Fat Mass (FM), over a 40 year period in the participants of the Loughborough Alumni study. With specific reference to the reflection these variables have upon health status. METHODS: About 1200 Physical Education students entering Loughborough College of Education between 1958 and 1967 underwent a series of standardised testing and were invited to return for a follow up study in 1999. A returning sub-sample of 118 participants underwent a similar battery of tests to those originally carried out. Participants were all adult males, age 19.7 (+1.8) years, classified as fit and healthy upon initial testing and a mean age of 55.0 (+3.7) years at re-test. Morphological dimensions were assessed using protocol ratified by the IWGK and physiological status assessed using the AD NFS guidelines, supplemented where necessary with procedures from the CPAFLA. RESULTS: As expected, body composition of the participants changed in relation to the ageing process, mass increased and composition altered. When the results are displayed as a change in BMI the participants went from being classified as Normal weight (22.6) to Overweight (26.7), which reflects the change in mass (+12kg). This is a 17.2% change in BMI moving the mean classification up a single level. However when the body composition was analysed the % BF showed a much larger increase of 66%, while the change in FM showed an increase of 93%; approximately 9Kg of the overall 12kg change in mass. Abdominal girth showed a significant (p<0.05) increase of 21cm: 8.5 inches while Blood Pressure (127/77-131/86 mmHg) showed significant but non-clinical increases. Indices of general fitness (strength, muscular endurance, power, flexibility) all showed significant decreases, as did lung function (FVC). CONCLUSIONS: The ability of BMI to detect changes in body composition in adult males who are initially identified as fit and healthy individuals does not reflect the larger changes in actual BF. This has major implications for an ageing population who may be at a higher risk of CHD, diabetes, hyperlipidemia, and hypertension than is indicated by their BMI.

The Failure of Torcetrapib

Hopes have been running high that treatments aimed at raising HDL levels would soon help to reduce the large burden of cardiovascular disease that remains in patients at high risk of CHD who are now treated with statins. The unexpected and premature termination of the ILLUMINATE study has dashed those hopes. This study was designed to determine the clinical outcome of raising HDL by treatment with the CETP inhibitor torcetrapib in combination with atorvastatin. It had enrolled approximately 15 000 patients at high CHD risk who were randomized to treatment with torcetrapib (60 mg) plus atorvastatin versus atorvastatin alone (10 to 80 mg). As reported in the Wall Street Journal (Dec 4th), the study was terminated abruptly and unexpectedly after a little more than a year of treatment, because of an excess of deaths in the torcetrapib/atorvastatin versus atorvastatin groups (82 versus 51, respectively). Increases in heart failure, angina, and revascularization procedures were also observed. So is this the awakening from a dream of a highly effective way to raise HDL, or is it simply a nightmare created by unintended pharmacological effects of this particular CETP inhibitor? There is no clear answer to this question yet, but it is of interest to trace the development of CETP inhibitors, to reflect on the potential underlying reasons for the failure, and to ask if there is a way forward. The idea of inhibiting CETP as a therapy to increase HDL and lower LDL levels emerged from studies that elucidated human genetic deficiency of CETP in the Japanese population.1,2 Heterozygotes with about 40% reductions in CETP had mean 30% increases in HDL levels and no changes in LDL-C, whereas homozygotes with complete deficiency had HDL increases of more than 100%, and 40% decreases in LDL-C and apoB levels, as well as decreased …

Metabolic syndrome and coronary heart disease risk in a population-based study of middle-aged men from France and Northern Ireland: A nested case-control study from the PRIME cohort

Metabolic Syndrome (MetS) was found associated with an increased CHD risk in several studies but data about this relationship in Southern Europe are lacking. We studied the association of MetS according to three different indexes (the National Cholesterol Education Program's definition (NCEP), a modified World Health Organization's definition (WHO) and the recent International Diabetes Federation's definition (IDF)) with CHD risk in a case-control study nested within the PRIME cohort, composed of subjects from France (Southern Europe) and Belfast (Northern Europe). The PRIME prospective study is composed of 10 592 men, aged 50-59 at baseline and followed for 5 years. Subjects included in this nested case-control study were 296 cases of incident CHD and 540 controls, who remained free of CHD during the 5 years of follow-up of the PRIME cohort and matched for age, recruitment centre and recruitment date. All subjects had questionnaires and a medical examination at baseline, and a blood sample was taken. Using the IDF's, the WHO's and the NCEP's definitions respectively, the frequency of MetS was 38.9%, 35.5% and 29.7% in cases and 32.4%, 28.7% and 22.6% in controls. After adjustment for physical activity, smoking and drinking habits, MetS was associated with CHD risk whichever the definition used (ORIDF=1.41 [1.02-1.95], P<0.04, ORWHO=1.40 [1.01-1.94], P<0.05 and ORNCEP=1.46[1.04-2.04], P<0.04). These results were homogeneous in France (low risk of CHD) and Belfast (high risk of CHD). Our results add further evidence that MetS is predictive of CHD risk in middle-aged men from Northern and Southern Europe, and highlight differences between the three definitions studied.

Abstract 4168: Two Independent Apolipoprotein A5 Haplotypes Modulate Postprandial Lipoprotein Metabolism in a Caucasian Healthy Population.

Background: APOA5 plays an important role in plasma plasma triglyceride (TG) homeostasis. Five polymorphisms (1131T&gt;C, c.-3A&gt;G, c.56C&gt;G, IVS3+476G&gt;A, c.1259T&gt;C) in the APOA5 gene were found to define three common haplotypes (denoted APOA5 *1, APOA5 *2 and APOA5* 3) in Caucasian individuals. Our aim was to determine whether these haplotypes could modulate the postprandial response in young healthy males, in order to explain the higher risk of coronary artery disease (CHD) associated with less common alleles Design and methods: 84 apo E3E3 volunteers [63 with (-1131T and 56C) haplotype 1, 12 with (-1131C and 56C) haplotype 2 and 9 with (-1131T and 56G) haplotype 3] underwent a fat-load test consisting of 1 g of fat/kg body weight and 60,000 IU of vitamin A. Blood samples were taken at time 0 and every hour until the 6 th and every 2.5 hr until the 11 th . Cholesterol (Chol) and TG were determined in plasma and Chol, TG, Apo B-100, Apo B-48, and retinyl palmitate (RP) were determined in lipoprotein fractions. Results: Data of postprandial lipemia revealed that subjects with the haplotypes 2 and 3 had a higher area under the curve than subjects with the haplotype 1 of total plasma TG (0.28±0.1 and 0.31±0.1 vs 0.21±0.1 mmol/L s, p0.04), large triacylglycerol-rich lipoproteins (TRL)-TG (0.19±0.07 and 0.22±0.09 vs 0.10±0.04 mmol/L s, p=0.01), small TRL-TG (0.15±0.06 and 0.14±0.07 vs 0.9±0.05 mmol/L s, p=0.03), large TRL-Cho (0.05±0.01 and 0.06±0.01 vs 0.03±0.061 mmol/L s, p=0.04), and small apoB100 (639±315 and 219±158 vs 140±86, p=0.03). Conclusions : Our findings show that the presence of the haplotype 2 and 3 in the APO5 gene are associated with a higher postprandial response and could be involved in a higher risk of CHD.

Migraine With Aura Linked to Higher CHD Risk

Migraine With Aura Linked to Higher CHD Risk