Cholesterol and other lipids predict coronary heart disease and ischaemic stroke in the elderly, but only in those below 70 years.

The prediction of coronary heart disease (CHD) and stroke by total and low density lipoprotein (LDL) cholesterol in older persons remains problematical. This study tests the hypothesis that cholesterol and other risk factors may be differentially predictive of CHD and ischaemic stroke in older persons when they are segregated into different age groups. CHD and ischaemic stroke outcomes were recorded during 129 months follow-up in a cohort of 2805 men and women of 60 years and older. There were 899 CHD events (32/100) and 326 stroke events (12/100). Using Cox proportional hazards, outcomes were modelled for the total cohort and for age groups 60-69, 70-79, and 80+ years. Total cholesterol, LDL cholesterol, serum apo-B, total cholesterol/high density lipoprotein (HDL) cholesterol and apo-B/apo-A1 were significant predictors of CHD in the total cohort, but significant only in the sub-group of 60-69 years. The respective hazard ratios (CI 95%) were 1.21 (1.09-1.35), 1.21 (1.09-1.35), 1.25 (1.13-1.39), 1.25 (1.14-1.37) and 1.21 (1.10-1.38). Similar findings were applicable with respect to ischaemic stroke in the age group of 60-69 years. Total cholesterol predicted CHD in men above a threshold value of 7.06 mmol/l and in women above 7.8 mmol/l, but with stroke the prediction was incremental. Other risk factors such as HDL cholesterol, triglycerides, lipoprotein(a), diabetes, hypertension and smoking predicted CHD, although only HDL and hypertension similarly predicted ischaemic stroke. The findings support a case for cholesterol testing in older subjects up to 70 years, in whom there is ancillary evidence of CHD and stroke prevention through treatment designed to reduce LDL cholesterol.     

Associations of resting heart rate with concentrations of lipoprotein subfractions in sedentary men

In major prospective studies it has been reported that high heart rate at rest predicts the development of coronary heart disease (CHD) or cardiovascular disease (CVD) in men, but the mechanisms producing these relationships are unknown. Since lipoprotein levels contribute strongly to the risk of CHD and CVD, we examined the relationship of resting heart rate to plasma concentrations of high-density (HDL), low-density (LDL), and very low-density (VLDL) lipoproteins, apolipoprotein (apo) A-I and A-II, and serum concentrations of lipoprotein subfractions in 81 men to determine if atherogenic lipoproteins could potentially induce the reported association of heart rate with development of CHD or CVD. The significant (p less than or equal to .05) Spearman's correlations for resting heart rate vs HDL2 mass (rs = -.24), HDL3 mass (rs = -.40), HDL cholesterol (rs = -.36), apo A-I (rs = -.29), triglycerides (rs = .31), VLDL cholesterol (rs = .24), VLDL mass (rs = .27), and LDL mass of Sof 0-7 subfraction (rs = .30) lend support to our hypothesis of lipoprotein-induced relationships of CHD with heart rate. The correlations for resting heart rate vs triglycerides, HDL cholesterol, HDL3 mass, VLDL mass, and LDL mass of Sof 0-7 subfraction remain significant when adjusted for adiposity, age, smoking habits, diet, and physical fitness as measured by maximum aerobic power (VO2 max) or submaximal heart rate during a graded exercise test.     

Relationship between obesity,insulin resistance,and coronary heart disease risk

OBJECTIVES: The study goals were to: 1) define the relationship between body mass index (BMI) and insulin resistance in 314 nondiabetic, normotensive, healthy volunteers; and 2) determine the relationship between each of these two variables and coronary heart disease (CHD) risk factors. BACKGROUND: The importance of obesity as a risk factor for type 2 diabetes and hypertension is well-recognized, but its role as a CHD risk factor in nondiabetic, normotensive individuals is less well established. METHODS: Insulin resistance was quantified by determining the steady-state plasma glucose (SSPG) concentration during the last 30 min of a 180-min infusion of octreotide, glucose, and insulin. In addition, nine CHD risk factors: age, systolic blood pressure, diastolic blood pressure (DBP), total cholesterol, triglycerides (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein cholesterol concentrations, and glucose and insulin responses to a 75-g oral glucose load were measured in the volunteers. RESULTS: The BMI and the SSPG concentration were significantly related (r = 0.465, p < 0.001). The BMI and SSPG were both independently associated with each of the nine risk factors. In multiple regression analysis, SSPG concentration added modest to substantial power to BMI with regard to the prediction of DBP, HDL cholesterol and TG concentrations, and the glucose and insulin responses. CONCLUSIONS: Obesity and insulin resistance are both powerful predictors of CHD risk, and insulin resistance at any given degree of obesity accentuates the risk of CHD and type 2 diabetes.     

Plasma phospholipid transfer protein activity, a determinant of HDL kinetics in vivo

OBJECTIVE: Phospholipid transfer protein (PLTP) is an important regulator in the transport of surface components of triglyceride-rich lipoprotein (TRL) to high density lipoprotein (HDL) during lipolysis and may therefore play an important role in regulating HDL transport. In this study we investigated the relationship of plasma PLTP activity with HDL metabolism in men. DESIGN AND METHODS: The kinetics of HDL LpA-I and LpA-I:A-II were measured using intravenous administration of [D3]-leucine, gas chromatography-mass spectrometry (GCMS) and a new multicompartmental model for HDL subpopulation kinetics (SAAM II) in 31 men with wide-ranging body mass index (BMI 18-46 kg/m2). Plasma PLTP activity was determined as the transfer of radiolabelled phosphatidylcholine from small unilamellar phosphatidylcholine vesicles to ultracentrifugally isolated HDL. RESULTS: PLTP activity was inversely associated with LpA-I concentration and production rate (PR) after adjusting for insulin resistance (P < 0.05). No significant associations were observed between plasma PLTP activity and LpA-I fractional catabolic rate (FCR). In multivariate analysis, including homeostasis model assessment score (HOMA), triglyceride, cholesteryl ester transfer protein (CETP) activity and PLTP activity, PLTP activity was the only significant determinant of LpA-I concentration and PR (P = 0.020 and P = 0.016, respectively). CONCLUSIONS: Plasma PLTP activity may be a significant, independent determinant of LpA-I kinetics in men, and may contribute to the maintenance of the plasma concentration of these lipoprotein particles in setting of hypercatabolism of HDL.     

Associations between high-density lipoprotein cholesterol and both stroke and coronary heart disease in the Asia Pacific region.

BACKGROUND: The inverse relationship between high-density lipoprotein (HDL) cholesterol and coronary heart disease (CHD) is well established. Questions remain about the association between HDL cholesterol and stroke, particularly for stroke subtypes. METHODS AND RESULTS: Cox survival models were applied to individual participant data from 25 cohort studies (about 80 000 subjects), with a median of 6.8 years follow-up. After adjustment for age and regression dilution, hazard ratios (95% confidence intervals) for a 1 standard deviation (SD) lower level of HDL cholesterol (0.4 mmol/L) were: for CHD events, 1.39 (1.22-1.57); for ischaemic stroke, 0.90 (0.75-1.07), and for haemorrhagic stroke, 0.89 (0.74-1.07). As total cholesterol (TC) increased relative to HDL cholesterol, the risk of CHD increased, the risk of ischaemic stroke was unchanged but the risk of haemorrhagic stroke decreased. A 1 SD increase in TC/HDL cholesterol (1.63 units) was associated with a 27% decrease in the risk of haemorrhagic stroke (95% confidence interval, 7-44%). CONCLUSION: There is clear evidence of potential benefit for CHD of increases in HDL cholesterol and decreases in TC relative to HDL cholesterol, but no evidence of an association between either HDL cholesterol or TC/HDL cholesterol and ischaemic stroke. Increasing HDL cholesterol relative to TC may increase the risk of haemorrhagic stroke.     

Relationship between plasma phospholipid transfer protein activity and HDL subclasses among patients with low HDL and cardiovascular disease

Low levels of high density lipoproteins (HDL) are associated with an increased risk for premature cardiovascular disease. The plasma phospholipid transfer protein (PLTP) is believed to play a critical role in lipoprotein metabolism and reverse cholesterol transport by remodeling HDL and facilitating the transport of lipid to the liver. Plasma contains two major HDL subclasses, those containing both apolipoproteins (apo) A-I and A-II, Lp(A-I, A-II), and those containing apo A-I but not A-II, Lp(A-I). To examine the potential relationships between PLTP and lipoproteins, plasma PLTP activity, lipoprotein lipids, HDL subclasses and plasma apolipoproteins were measured in 52 patients with documented cardiovascular disease and low HDL levels. Among the patients, plasma PLTP activity was highly correlated with the percentage of plasma apo A-I in Lp(A-I) (r=0.514, p<0.001) and with the apo A-I, phospholipid and cholesterol concentration of Lp(A-I) (r=0.499, 0.478, 0.457, respectively, p≤0.001). Plasma PLTP activity was also significantly correlated with plasma apo A-I (r=0.413, p=0.002), HDL cholesterol (r=0.308, p=0.026), and HDL₂ and HDL₃ cholesterol (r=0.284 and 0.276, respectively, p<0.05), but no significant correlation was observed with Lp(A-I, A-II), plasma cholesterol, triglycerides, or apo B, very low density lipoprotein cholesterol or low density lipoprotein cholesterol. These associations support the hypothesis that PLTP modulates plasma levels of Lp(A-I) particles without significantly affecting the levels of Lp(A-I, A-II) particles.     

Serum phospholipid transfer protein activity and genetic variation of the PLTP gene.

The inverse relationship between serum levels of high density lipoproteins (HDL) and risk of coronary heart disease is well established. The phospholipid transfer protein (PLTP) promotes the transfer of phospholipids between lipoproteins and modulates HDL size and composition. It thus plays a central role in HDL metabolism. Serum PLTP activity was measured in 400 healthy Finnish individuals in order to determine normal PLTP serum values. PLTP activity increased with age (P<0.001), so that the PLTP activity was 3.81+/-0.84 micromol/ml per h (mean +/- S.D., n = 52) for men and 3.97+/-0.11 micromol/ml per h (n = 52) for women in the youngest age group (25-35 years), while it was 6.77+/-0.17 micromol/ml per h (n = 45) for men and 6.68+/-0.15 micromol/ml per h (n = 40) for women in the oldest age group (56-65 years). PLTP activity correlated significantly (P<0.001) with body mass index (r = 0.22), serum total cholesterol (r = 0.17), the ratio of HDL-cholesterol/total cholesterol (r = -0.20), triglycerides (r = 0.20), apo A-II (r = 0.20), and gamma glutamyl transferase (r = 0.22) values. Serum PLTP activity correlated negatively (r = -0.20, P<0.001) with levels of apolipoprotein A-I in HDL particles that contained only apo A-I [Lp(A-I) particles]. The allelic frequencies of six intragenic polymorphisms, -79G/T, -56G/A, -37T/C, -31A/G, Phe2Leu, Arg121Trp, and two neutral polymorphisms, located in the immediate vicinity of the PLTP gene were determined. There were no significant associations between these polymorphisms and serum PLTP activity.     

Association between blood pressure, the treatment of hypertension, and cardiovascular risk factors in women

OBJECTIVE: To examine relationships of normal blood pressure (BP), hypertension and degree of BP control with cardiovascular disease (CVD) risk factors and predicted 10-year risks for coronary heart disease (CHD) and stroke. DESIGN: Cross-sectional survey. SETTING: 107 Marks and Spencer retail stores in the UK. PARTICIPANTS: 14,077 women, aged 30-64 years, screened for CVD risk factors between 1988 and 1991. MAIN OUTCOME MEASURES: Systolic (SBP) and diastolic (DBP) BP; total, high-(HDL) and low-density lipoprotein (LDL) cholesterol, ratio of total to HDL cholesterol (TC/HDL-C); triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein (a), glucose, body mass index, antihypertensive medication and predicted risks for CHD and stroke. Hypertension was defined as SBP > or = 140 mmHg and/or DBP > or = 90 mmHg and/or taking anti-hypertensive medication. Subjects were divided into normotensives with optimal (n = 6,599), normal (n = 3,170) and high normal (n = 2,184) BP levels, and hypertensives with adequate BP control (n = 228), untreated (n = 1,729) and inadequate BP control (n = 291). RESULTS: BP level was associated with other CVD risk factors among both normotensives and hypertensives. Women with inadequately controlled BP had the worst risk profile, followed by untreated hypertensives, those with adequately controlled BP and normotensives. Odds ratios for being in the top quintile of predicted 10-year CHD and stroke risks were 1, 2.7, 4.2, 8.5, 13.0, 18.9 for CHD; 1, 1.1, 5.8, 18.7, 20.6, 756 for stroke, for optimal, normal, high normal, adequate BP control, untreated and inadequate BP control groups respectively. CONCLUSIONS: Untreated hypertensives and women taking anti-hypertensive medication but with BP > or = 140/90 mmHg have the most atherogenic risk factor profiles. Effective management of BP and the associated CVD risk requires a multi-factorial approach, rather than addressing BP control in isolation.     

High-density lipoprotein (HDL) transport in the metabolic syndrome: application of a new model for HDL particle kinetics

CONTEXT: Reduced high density lipoprotein (HDL) concentration in the metabolic syndrome (MetS) is associated with increased risk of diabetes and cardiovascular disease and is related to defects in the kinetics of HDL apolipoprotein (apo) A-I and A-II. OBJECTIVE: The objective of the study was to investigate HDL apoA-I and apoA-II kinetics in nondiabetic men with MetS and lean controls by developing a model that describes the kinetics of lipoprotein (Lp)A-I and LpA-I:A-II particles. DESIGN: Twenty-three MetS men and 10 age-matched lean controls were investigated. ApoA-I and apoA-II tracer/tracee ratios were studied after iv d3-leucine administration using gas chromatography mass spectrometry. RESULTS: Compared with lean subjects, MetS subjects had accelerated catabolism of LpA-I (P < 0.001), LpA-I:A-II (P = 0.005), and apoA-II (P = 0.005); the production rate of LpA-I was also significantly elevated in MetS, so that the dominant changes in plasma concentrations were reduction in LpA-I:A-II (P < 0.001) and apoA-II (P < 0.05). Increased catabolism of LpA-I and LpA-I:A-II was directly related to increased waist circumference, hypertriglyceridemia, low HDL-cholesterol, small HDL particle size, hyperinsulinemia, and low phospholipid transfer protein (PLTP) activity; overproduction of LpA-I was significantly associated with increased waist circumference, insulin resistance, and low PLTP activity. CONCLUSIONS: MetS men exhibit hypercatabolism of the two major HDL lipoprotein particles, LpA-I and LpA-I:A-II, but selective overproduction of LpA-I maintains a normal plasma concentration of LpA-I. These kinetic perturbations are probably related to central obesity, insulin resistance, hypertriglyceridemia, and low plasma PLTP activity.     

Extent to which accepted serum lipid goals are achieved in a contemporary general medical population with coronary heart disease risk equivalents

This study examined lipid levels and the use of lipid-altering drugs in a contemporary general medical population without documented coronary heart disease (CHD) but with CHD risk equivalents. On the basis of present national guidelines, the following lipid values (in milligrams per deciliter) were considered optimal for this population: low-density lipoprotein cholesterol <100, high-density lipoprotein (HDL) cholesterol >or=40 in men and >or=50 in women, and non-HDL cholesterol <130 if triglycerides are >or=200. Of 44,052 active patients screened, 877 with CHD risk equivalents as defined by the Adult Treatment Panel III guidelines were identified. Most patients did not meet optimal lipid targets for low-density lipoprotein cholesterol (59%), HDL cholesterol (66%), and non-HDL cholesterol (72%). Indeed, 88% of patients did not meet >or=1 lipid goal. Statins were used in 57% of patients. In patients with low HDL cholesterol, only 4.7% were taking niacin and 4.9% fibrates. In the subgroup of patients with triglycerides >or=200 mg/dl, only 9.5% were taking fibrates and 8.2% niacin. In conclusion, the present analysis highlights the dramatic need to further improve preventive measures in a substantial proportion of high-risk patients with CHD risk equivalents.     

Sequential estrogen-progestin replacement therapy in healthy postmenopausal women: effects on cholesterol efflux capacity and key proteins regulating high-density lipoprotein levels

Thirty healthy postmenopausal women were randomized into 2 groups that received a sequential combined hormone-replacement therapy (HRT) (n = 18; conjugated equine estrogen 0.625 mg/d for 28 days and 5 mg of medroxyprogesterone acetate during the last 14 days) or placebo (n = 12). Plasma samples were collected before and during treatment (days 0, 15, 43, 71). High-density lipoprotein (HDL) lipid content, lipoprotein (Lp)A-I and LpA-I:LpA-II concentration, lecithin:cholesterol acyl transferase activity (LCAT), phospholipid transfer protein (PLTP) activity, and the plasma capacity to carry out cholesterol efflux from Fu5AH cells were measured. Most significant changes were found within the first 15 days after HRT. After 71 days of HRT, we found an increase in LpA-I lipoparticles (27%) and the following HDL lipids: phospholipids (21%), triglycerides (45%), and free cholesterol (43%), as well as an increase in cholesterol efflux (12.5%). PLTP activity, on the other hand, decreased 21% after 71 days of treatment. No significant changes in LCAT activity, HDL-cholesterol ester or LpA-I:LpA-II particles were found. Positive correlation between cholesterol efflux and the variables LpA-I and HDL-phospholipids were observed. PLTP was negatively correlated with apolipoprotein (apo) A-I, LpA-I, and LpA-I:LpA-II. In summary, our study, performed during 3 hormonal cycles, shows that HRT not only modifies HDL-cholesterol level, but also its lipid composition and HDL lipoparticle distribution. HRT enhances the plasma capacity to carry out cholesterol efflux from the Fu5AH system and decreases the activity of PLTP, a key protein regulating HDL levels. Considering the protocol sampling, these results represent mainly the estrogenic effect of HRT.     

Quantification of human plasma phospholipid transfer protein (PLTP): relationship between PLTP mass and phospholipid transfer activity

A sensitive sandwich-type enzyme-linked immunosorbent assay (ELISA) for human plasma phospholipid transfer protein (PLTP) has been developed using a monoclonal capture antibody and a polyclonal detection antibody. The ELISA allows for the accurate quantification of PLTP in the range of 25-250 ng PLTP/assay. Using the ELISA, the mean plasma PLTP concentration in a Finnish population sample (n = 159) was determined to be 15.6 +/- 5.1 mg/l, the values ranging from 2.30 to 33.4 mg/l. PLTP mass correlated positively with HDL-cholesterol (r = 0.36, P < 0.001), apoA-I (r = 0.37, P < 0.001), apoA-II (r = 0.20, P < 0.05), Lp(A-I) (r=0.26, P=0.001) and Lp(A-I/A-II) particles (r=0.34, P<0.001), and negatively with body mass index (BMI) (r = -0.28, P < 0.001) and serum triacylglycerol (TG) concentration (r = -0.34, P < 0.001). PLTP mass did not correlate with phospholipid transfer activity as measured with a radiometric assay. The specific activity of PLTP, i.e. phospholipid transfer activity divided by PLTP mass, correlated positively with plasma TG concentration (r=0.568, P<0.001), BMI (r=0.45, P<0.001), apoB (r = 0.45, P < 0.001). total cholesterol (r=0.42, P < 0.001), LDL-cholesterol (r = 0.34, P < 0.001) and age (r = 0.36, P < 0.001), and negatively with HDL-cholesterol (r= -0.33, P < 0.001), Lp(A-I) (r= -0.21, P < 0.01) as well as Lp(A-I/A-II) particles (r = -0.32, P < 0.001). When both PLTP mass and phospholipid transfer activity were adjusted for plasma TG concentration, a significant positive correlation was revealed (partial correlation, r = 0.31, P < 0.001). The results suggest that PLTP mass and phospholipid transfer activity are strongly modulated by plasma lipoprotein composition: PLTP mass correlates positively with parameters reflecting plasma high density lipoprotein (HDL) levels, but the protein appears to be most active in subjects displaying high TG concentration.     

Carotid intima-media thickness and coronary heart disease risk factors in a low-risk population.

OBJECTIVE: Coronary heart disease (CHD) risk factors have been consistently related to an increase in carotid intima-media thickness (IMT) in selected populations. However, few studies were population-based and furthermore little attention has been given to the influence of CHD risk factors on IMT in low-risk populations for CHD. DESIGN: We examined the association between carotid IMT and CHD risk factors in a large (n = 1013) and representative sample of middle-aged men and women in one of the European populations with the lowest CHD risk. METHODS: High-resolution B-mode ultrasonography of the common carotid arteries was performed. RESULTS: Age, smoking (not significant in women), body mass index, waist to hip ratio, systolic (SBP) and diastolic blood pressure, alcohol consumption, total and low-density lipoprotein cholesterol, triglycerides, glycaemia, fibrinogen (not significant in women), haematocrit (not significant in men) and insulin (not significant in women) were positively and significantly associated with mean IMT. High-density lipoprotein (HDL) cholesterol (not significant in women) was negatively and significantly associated with mean IMT. In a subsample of 355 men, IMT was not associated with angiotensin I-converting enzyme gene polymorphism. Multivariate analyses showed, in men, independent associations between mean IMT (0.61+/-0.11 mm) and age, pack-years, SBP, HDL cholesterol, alcohol and the interaction between age and alcohol. In women, only age and SBP were independently associated with mean IMT (0.58+/-0.09 mm). CONCLUSIONS: We found thinner IMT than those found in high-risk populations, suggesting that an increased IMT might reflect local atherosclerosis. Protective factors such as HDL cholesterol or regular and moderate alcohol consumption are probably important determinants of the early stages of atherosclerosis in these low-risk populations.     

The Dubbo study of the health of elderly: correlates of coronary heart disease at study entry

A prospective study of the health of elderly Australians recently commenced in Dubbo, NSW, the study population comprising 1,237 males and 1,568 females 60 years and older. The prevalence rates of coronary heart disease (CHD) and its associated risk factors have been examined in the baseline data. The age-standardized rate of CHD was 23.8/100 in males and 18.1/100 in females. The prevalence rate increased with age until 79 years in males, thereafter declining. The rate increased steadily with age in females. In a multiple logistic model, the following possible predictors of CHD were included: age, cigarette smoking, use of alcohol, exercise, religiosity, years of education, hypertension, diabetes, family history of CHD, body mass index, lipid and lipoprotein variables. The presence of CHD in males was significantly predicted by age, hypertension (odds ratio, OR = 1.40), family history (OR = 2.05), and high density lipoprotein (HDL) cholesterol (OR = 0.78). The significant predictors in females were age, years of education (OR = 0.82), hypertension (OR = 1.45), family history (OR = 1.77), serum triglycerides (OR = 1.30), and HDL cholesterol (OR = 0.73). Hypertension was found to be a stronger predictor of CHD in the younger age group (60-69 years), while diabetes was a predictor of CHD in older males (70-79 years). Our findings require confirmation in the prospective study now in progress.     

Recent corticosteroid use and recent disease activity: independent determinants of coronary heart disease risk factors in systemic lupus erythematosus?

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by a markedly elevated risk for coronary heart disease (CHD), the exact pathogenesis of which is unknown. In particular, the causal roles of corticosteroid therapy and SLE disease activity, and whether their putative effects are mediated through conventional risk factors, remain unclear. METHODS: Data abstracted retrospectively from the charts at 11,359 clinic visits for 310 patients with SLE to the Montreal General Hospital were used to investigate the associations of recent corticosteroid dose and recent Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score with 8 CHD risk factors (total serum cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein cholesterol, apolipoprotein B [Apo B], triglycerides, systolic blood pressure [BP], body mass index, and blood glucose) and the aggregate estimate of 2-year CHD risk. Separate multivariable linear regression models estimated the mutually-adjusted effects of average daily corticosteroid dose and average SLEDAI score within the past year on the current level of each risk factor while adjusting for age, sex, cumulative damage score, disease duration, and, where appropriate, use of relevant medications. RESULTS: Higher past-year corticosteroid dose was independently associated with significantly higher overall 2-year CHD risk and with higher levels of all 8 individual risk factors. Higher past-year lupus disease activity was independently associated with higher overall 2-year CHD risk, lower HDL cholesterol, and higher values of systolic BP, Apo B, triglycerides, and blood glucose. CONCLUSION: In SLE, both recent use of corticosteroids and recent lupus activity are independently associated with higher values of several well-recognized CHD risk factors and overall 2-year CHD risk.     

Low- and high-density lipoprotein cholesterol and ischemic cerebrovascular disease: the bezafibrate infarction prevention registry

BACKGROUND: Despite increasing evidence that beta-hydroxy-beta-methyglutaryl coenzyme A reductase inhibitors reduce the incidence of stroke in patients with coronary heart disease (CHD), the associations between blood lipid levels and cerebrovascular disease (CVD) are not clear. OBJECTIVE: To evaluate whether blood cholesterol level and its fractions are risk factors for stroke in a large group of patients with CHD. METHODS: We followed up 11 177 patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study, a secondary prevention randomized clinical trial of lipid modification, and had no history of stroke for subsequent CVD. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic CVD, of whom 487 had verified ischemic stroke or transient ischemic attack (TIA). RESULTS: Increases in age-adjusted rates of both nonhemorrhagic CVD and verified ischemic stroke or TIA were identified with increasing cholesterol and low-density lipoprotein cholesterol levels, decreasing high-density lipoprotein cholesterol levels, and decreasing percentage of total serum cholesterol contained in the HDL moiety. In logistic regression models, adjusting for clinical covariates, the following odds ratios (95% confidence intervals) were identified for lipid values in the upper vs lower tertile for the end point of nonhemorrhagic CVD: total cholesterol, 1.43 (1.20-1.70); low-density lipoprotein cholesterol, 1.52 (1.27-1.81), high-density lipoprotein cholesterol, 0.84 (0.70-1.00); and percentage of serum cholesterol contained in HDL, 0.69 (0.58-0.83). Similar trends appeared for the end point of verified ischemic stroke or TIA. CONCLUSION: These findings clearly support the role of total cholesterol and its fractions in prediction of ischemic CVD among patients with established CHD.     

Sex and time differences in the associations of non-high-density lipoprotein cholesterol versus other lipid and lipoprotein factors in the prediction of cardiovascular death (The Rancho Bernardo Study)

Non-high-density lipoprotein (HDL) cholesterol (total cholesterol [TC] minus HDL cholesterol) has been suggested as the preferred lipid fraction to predict cardiovascular disease. We compared the ability of lipids, lipoproteins, the ratio of total to HDL cholesterol (TC/HDL), and non-HDL cholesterol to predict fatal coronary heart disease (CHD) and cardiovascular disease in 1,386 women and 1,094 men (mean age 69 years). After 10 years, there were more deaths in men (n = 310) than women (n = 268), but the proportions of deaths attributed to CHD (23% and 25%, respectively) and cardiovascular disease (48% and 47%) were similar. In men, age-adjusted values for non-HDL cholesterol, TC/HDL ratio, and triglycerides each predicted a significantly increased risk of CHD and cardiovascular disease; none of these associations was independent of pack-years of smoking, systolic blood pressure, fasting plasma glucose, body mass index, and physical activity. In women, age-adjusted non-HDL cholesterol levels did not predict CHD or cardiovascular disease events before or after adjusting for these covariates and for estrogen replacement therapy. In women, only the ratio of TC to HDL cholesterol predicted CHD and cardiovascular disease deaths independent of estrogen use and other risk factors. Observed associations were sensitive to time, being evident in women at 3 and 5 years, and lost thereafter, but not apparent before 10 years in men. Thus, non-HDL cholesterol is not superior to individual lipids, lipoproteins, or their ratios in the prediction of cardiovascular death in older adults.     

The triglyceride issue: a view from Framingham

Triglycerides make up the overwhelming proportion of dietary fat consumed in the United States and other industrialized nations. Triglyceride elevation is directly associated with relative weight and age in both sexes, oral contraceptive use in women, and the development of diabetes mellitus. Triglyceride elevations are a highly significant independent risk factor for coronary heart disease (CHD) in women. They appear to be important in men with low high-density lipoprotein (HDL) cholesterol (less than 40 ml/dl). Dangerously high levels of triglyceride are associated with a high total cholesterol/HDL cholesterol ratio, which is an excellent indicator of CHD risk in both sexes. Individuals with elevated triglycerides should be considered at risk for CHD unless the total cholesterol/HDL cholesterol ratio is under 3.5. In practice, however, only about 10% of individuals with elevated triglycerides prove to have such low total cholesterol/HDL cholesterol ratios.     

Lipids in type 2 diabetes

Type 2 diabetes increases the risk of cardiovascular disease two- to fourfold compared to the risk in nondiabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors, the cause for an excess risk of cardiovascular disease remains unknown. Lipid and lipoprotein abnormalities in type 2 diabetes include particularly elevated levels of total and very low-density lipoprotein triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. Total and low-density lipoprotein (LDL) cholesterol levels are usually normal if glycemic control is adequate but LDL particles are small and dense. According to prospective population-based studies, total cholesterol is a similar risk factor for coronary heart disease (CHD) in patients with type 2 diabetes as it is in nondiabetic subjects. High total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in patients with type 2 diabetes than in nondiabetic subjects. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol by statins, and the lowering of total triglycerides and the raising of HDL cholesterol by fibrates, are at least as beneficial in diabetic patients as in nondiabetic subjects in the prevention of cardiovascular disease.     

Moderate alcohol consumption and postprandial plasma lipids in men with different risks for coronary heart disease

BACKGROUND: Moderate alcohol consumption is associated with a reduced coronary heart disease (CHD) risk. Epidemiologic studies have provided conflicting data which suggests that CHD protection may be modulated or may not be modulated by a person's CHD risk profile. METHODS: We examined the effects of moderate alcohol consumption (35 g/day) on postprandial lipoprotein metabolism in two groups of healthy middle-aged men who had different plasma total cholesterol, triglyceride concentrations, and body mass index (BMI), which are three major risk factors for CHD; 11 men had lower plasma lipids and BMI (L-men) and 11 men had higher plasma lipids and BMI (H-men). The effects of alcohol on postprandial lipoprotein metabolism were studied in a crossover design after an acute moderate alcohol intake both after a period of abstinence (alcohol-free beer) and after a period of moderate alcohol consumption (alcohol containing beer). RESULTS: Moderate alcohol consumption changed plasma total cholesterol, total triglycerides, and HDL composition in the postprandial period. Alcohol-induced changes were essentially the same over time in both L-men and H-men. However, changes occurred at a different overall plasma concentration for total cholesterol and total triglycerides. Also, the postprandial response to an acute moderate alcohol dose after a period of abstinence seemed not to essentially differ from the response to an acute moderate alcohol dose after a 4-week period of moderate alcohol consumption. CONCLUSIONS: These results suggest that men who differ in risk for CHD, based on plasma lipids and BMI, but without previous or underlying disease, have a similar postprandial lipid response to a moderate dose of alcohol.