Serum calcium and phosphorus associate with the occurrence and severity of angiographically documented coronary heart disease, possibly through correlation with atherogenic (apo)lipoproteins.

The associations of serum calcium and phosphorus concentrations as well as other cardiovascular risk factors were investigated in relation to the existence and severity of coronary heart disease (CHD) in 260 clinically stable, angiographically defined CHD patients aged 40-70 years. The subjects were classified as CHD(+) cases if one or more coronary arteries had a significant stenosis (> or =70%) and CHD(-) controls if there was no stenosis (< or =10%) in any artery. The severity of coronary occlusion was scored on the basis of the number and extent of lesions, as normal, mild, moderate or severe. Fasting serum concentrations of electrolytes, lipids and (apo)lipoproteins were determined. The concentrations of serum total calcium (2.41 +/-0.14 vs. 2.33 +/- 0.22 mmol/L, p < or = 0.05), albumin-corrected calcium (2.33 +/- 0.25 vs. 2.23 +/- 0.25 mmol/L, p < or = 0.01), phosphorus (1.32 +/-0.21 vs. 1.25 +/- 0.17 mmol/L, p < or = 0.007) and the ion product of calcium and phosphorus (3.16 +/- 0.58 vs. 2.91 +/- 0.50, p < or =0.0001) were significantly higher in the CHD(+) compared to the CHD(-) group. Patients with CHD compared with controls had increased serum levels of triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), lipoprotein(a) [Lp(a)] and decreased serum levels of high-density lipoprotein (HDL)-C and apoAI. Multiple logistic regression analysis showed strong and significant association between diabetes mellitus (odds ratio, OR = 5.24, p < or = 0.0001), male gender (OR = 8.84, p < or =0.0001), Lp(a) (OR = 1.014, p < or =0.006), hypertension (OR = 2.61, p < or =0.02), apoB (OR = 1.031, p < or =0.001), age (OR = 1.055, p < or =0.003), phosphorus (OR = 2.438, p < or =0.01), albumin-adjusted calcium (OR = 1.532, p < or =0.05), cholesterol (OR = 1.009, p < or =0.05) and the occurrence of CHD. On the basis of bivariate correlation analysis, serum-adjusted calcium was positively correlated with the levels of cholesterol (r = 0.285, p < or =0.0001), LDL-C (r = 0.320, p < or =0.0001), Lp(a) (r = 0.173, p < or = 0.005), apoB (r = 0.237, p < or =0.0001), LDL-C/apoB ratio (r = 0.180, p < or= 0.007), apoAI (r = 0.181, p < or =0.003) and inversely to HDL-C (r = -0.146, p < or =0.02) and HDL-C/apoAI ratio (r = -0.263, p < or =0.0001). Serum phosphorus concentration was a significant correlate of triglyceride (r = 0.199, p < or =0.001) and Lp(a) (r = 0.129, p < or =0.04). The results demonstrated that serum calcium and phosphorus are associated with the prevalence and severity of CHD, probably through correlation with atherogenic lipids and (apo)lipoproteins. Serum calcium and phosphorus and their ion product were also independent risk factors for CHD.     

Lack of association between lipoprotein(a) and coronary artery calcification in the Genetic Epidemiology Network of Arteriopathy (GENOA) study

OBJECTIVE: To investigate the relationship between lipoprotein(a) [Lp(a)] levels and the extent of coronary atherosclerosis in a cohort that consisted predominantly of hypertensive patients. PATIENTS AND METHODS: Patients were ascertained through sibships that contained at least 2 individuals with essential hypertension diagnosed before the age of 60 years. The 10-year coronary heart disease (CHD) risk was estimated on the basis of the Framingham risk equation. Serum Lp(a) was measured by an immunoturbidimetric assay. Coronary artery calcification (CAC) was measured noninvasively by electron beam computed tomography and CAC score calculated using the Agatston score. RESULTS: Patients included 765 non-Hispanic, white individuals (59% women) participating in the Genetic Epidemiology Network of Arteriopathy study. The mean +/- SD age of the patients was 62 +/- 8 years, and 77% had hypertension. The prevalence of detectable CAC was 87% in men and 60% in women. The CAC scores did not differ significantly across quintiles of Lp(a) levels in either men or women. In a multiple regression model that included conventional risk factors, Lp(a) levels were not related to CAC quantity in either sex. No significant interactions were noted between Lp(a) levels and the conventional risk factors in the prediction of CAC quantity. When stratified on the basis of the 10-year CHD risk, 26.5% of the patients were low risk (< 6%), 60.5% were intermediate risk (6%-20%), and 12.9% were high risk (> 20%). Lipoprotein(a) was not associated with CAC quantity within subgroups based on 10-year CHD risk. CONCLUSION: In this cohort enriched with hypertensive patients, the estimated 10-year CHD risk did not appear to modify the lack of an association between Lp(a) levels and CAC.     

Predicting coronary heart disease risk using the Framingham and PROCAM equations in dyslipidaemic patients without overt vascular disease

AIM: To compare the Framingham and Prospective Cardiovascular Munster (PROCAM) risk calculations. METHODS: We calculated the risk in 234 dyslipidaemic patients without overt vascular disease and in different subgroups. For example, the proportion of patients with coronary heart disease (CHD) risk >or= 20%, the effect of including the family history (FaHist) and of adjusting raised triglyceride (TG) levels. RESULTS: The Framingham risk was significantly (p < 0.0001) higher than the PROCAM risk (with and without including the FaHist) in different subgroups and when the TGs were adjusted to 1.7 mmol/l. The percentage of patients with CHD risk >or= 20% calculated by the Framingham (based on systolic or diastolic blood pressure) and PROCAM equations was 21.4% or 23.1% and 16.2% respectively. In the tertile with the highest PROCAM risk, the Framingham score was significantly greater than the PROCAM risk only when the FaHist was included in the Framingham calculation. When we analysed risk by gender, the Framingham score did not differ but the PROCAM risk was significantly (p < 0.0001) greater in men. When TG values were adjusted to 1.7 mmol/l, the predicted risk using PROCAM changed by 0% to -2% in all subgroups. CONCLUSIONS: In dyslipidaemic patients without overt vascular disease the Framingham model predicted a higher risk than PROCAM. Thus, the Framingham equation probably leads to substantial overtreatment compared with PROCAM. However, according to the literature, even the PROCAM equation may overestimate risk. This has considerable cost implications. New more accurate risk engines are needed to calculate risk in dyslipidaemic patients without overt vascular disease.     

The ratio of apoB/apoAI, apoB and lipoprotein(a) are the best predictors of stable coronary artery disease.

BACKGROUND: The ratio of low- to high-density lipoprotein-cholesterol (LDL-C/HDL-C) conventionally represents the balance of proatherogenic and anti-atherogenic lipids. However, growing evidence supports the idea that the ratio of apolipoprotein (apo) B/apoAI is a better index for risk assessment of coronary artery disease (CAD). The aim of this study was to evaluate the efficiency of advanced profile of serum (apo)lipoproteins for predicting stable CAD in secondary prevention. METHODS: The study subjects, 138 men and 126 women aged 40-70 years, were classified as CAD cases or controls, according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and extent of lesions in coronary arteries. Serum (apo)lipoproteins were measured by immunoturbidometric and electrophoresis methods. RESULTS: Patients with CAD compared with controls had increased serum levels of triglycerides (2.6+/-2.0 vs. 2.0+/-1.2 mmol/L, p< or =0.005), apoB (1.36+/-0.31 vs. 1.19+/-0.24 g/L, p< or =0.0001), lipoprotein(a) [Lp(a)] (0.69+/-0.60 vs. 0.43+/-0.31 g/L, p< or =0.0001) and apoB/apoAI ratio (1.07+/-0.32 vs. 0.87+/-0.18, p< or =0.0001), and decreased serum levels of HDL-C (1.02+/-0.29 vs. 1.11+/-0.34 mmol/L, p< or =0.03), apoAI (1.32+/-0.22 vs. 1.37+/-0.19 g/L, p< or =0.04) and LDL-C/apoB ratio (0.91+/-0.32 vs. 1.02+/-0.25 mmol/g, p< or =0.01). Multiple logistic regression analysis after adjusting for major risk factors showed that the apoB/apoAI ratio, apoB and Lp(a) were among seven significant and independent determinants of CAD. The area under the receiver operating characteristic (ROC) curves (AUC) as a relative measure of test efficiency was highest and significant for the apoB/apoAI ratio (AUC=0.71, p< or =0.0001), apoB (0.67, p< or =0.0001), Lp(a) (0.63, p< or =0.001), the LDL-C/apoB ratio (0.62, p< or =0.006), triglycerides (0.62, p< or =0.004) and apoAI (0.58, p< or =0.05). ANOVA analysis showed significant association for the apoB/apoAI ratio, apoB, Lp(a) and triglycerides, and moderate association for total cholesterol and its subfractions, with the severity of CAD. CONCLUSIONS: The results indicate that the apoB/apoAI ratio, apoB and Lp(a) are independent risk factors for CAD and are superior to any of the cholesterol ratios. We suggest using the apoB/apoAI ratio as the best marker of CAD in clinical practice.     

原发性高血压合并冠心病患者脂蛋白(a)的变化

目的 探讨原发性高血压(EH)合并冠心病患者血清脂蛋白(a)[Lp(a)]水平的变化及其临床意义.方法 选择老年EH患者159例,根据冠状动脉造影结果分为单纯EH组73例和合并冠心病组86例,检测其空腹血糖、肌酐、总胆固醇、甘油三酯、LP(a)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),计算体重指数.结果 与单纯EH组相比,Lp(a)水平在EH合并冠心病组明显增高[(0.34±0.12)、(0.48±0.18)mmol/L,t=-11.367,P＜0.05],在EH合并冠心病组中随冠状动脉病变程度的加重Lp(a)水平呈增高趋势[单支、双支、多支及弥漫病变组分别为(0.34±0.14)、(0.46±0.15)、(0.66±0.12)mmol/L,F=31.842,P=0.012].结论 EH患者Lp(a)水平与冠心病的发生及其严重程度相关.Lp(a)作为冠心病的危险因素,可以预测冠状动脉病变的严重程度.

Abstract：

Objective To study the changes of lipoprotein(a)[LP(a)] in patients with essential hypertension(EH) and coronary heart disease(CHD).Methods One hundred and fifty-nine EH older patients were recruited in the study.Eighty-six elderly patients were diagnosed as EH combined with CHD,and 73 patients were diagnosed as simple EH.All patients were tested for the fasting blood glucose(FBG),creatinine(Cr),total cholesterol(TC),triglyceride(TG),HDL-C,LDL-C,LP(a),and the body mass index(BMI) was calculated.Results Plasma Lp(a) increased(0.48±0.18)mmol/L in the EH combined with CHD patients,which were significantly higher than the increasing of(0.34±0.12) mmol/L in the simple EH patients(t=-11.367,P＜0.05).The level of plasma Lp(a) increased with the severity of the stenosis of the coronary artery(Lp(a):(0.37±0.14) mmol/L in single arterial branch stenoses,(0.46±0.15)mmol/L in double arterial branch stenoses,(0.66±0.12)mmol/L in triangle arterial branch stenoses,F=31.842,P=0.012).Conclusion The Lp(a) concentration in patients with EH are correlated with the occurrence and severity of coronary heart disease.As a risk of coronary heart disease,Lp(a) can predict the severity of coronary artery stenosis.     

The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U.K. men

In the present study, we have determined the relative frequency of the R46L, I474V and E670G variants in the PCSK9 (protein convertase subtilisin/kexin type 9) gene and its association with plasma lipid levels and CHD (coronary heart disease) in healthy U.K. men and patients with clinically defined definite FH (familial hypercholesterolaemia). Genotypes were determined using PCR and restriction enzyme digestion in 2444 healthy middle-aged (50-61 years) men from the prospective NPHSII (Second Northwick Park Heart Study), with 275 CHD events (15 years of follow-up), and in 597 U.K. FH patients from the Simon Broome Register. In the NPHSII healthy men, the R46L genotype distribution was in Hardy-Weinberg equilibrium and the frequency of 46L was 0.010 [95% CI (confidence interval), 0.007-0.013], with one man homozygous for the 46L allele. There was significant association of the 46L allele with lower mean (S.D.) total cholesterol [5.74 (1.01) mmol/l for RR compared with 5.26+/-1.03 mmol/l for RL; P=0.001], apolipoprotein B [0.87 (0.24) g/l for RR compared with 0.75 (0.26) g/l for RL; P<0.0001] and low-density lipoprotein cholesterol [4.01 (0.95) mmol/l for RR compared with 3.62 (0.97) mmol/l for RL; P=0.02]) levels, after adjustment for age, general medical practice, smoking, body mass index and systolic blood pressure. As expected, 46L carriers had a low risk of definite or possible CHD [hazard ratio, 0.46 (95% CI, 0.11-1.84)], but this was not statistically significant (P=0.27). Two other common PCSK9 variants I474V [V allele frequency, 0.179 (95% CI, 0.17-0.19)] and E670G [G allele frequency, 0.034 (CI, 0.03-0.04)] were not associated with any significant effects on lipid levels or CHD risk. In FH patients, the frequency of 46L was 0.003 (95% CI, 0.00-0.01), which was significantly lower (P=0.037) than the healthy subjects. In the four FH patients carrying 46L, mean untreated total cholesterol levels were not different (P=0.91) in carriers and non-carriers (median, 10.3 mmol/l compared with 10.2 mmol/l respectively, after adjustment for age, gender and mutation type). In conclusion, the PCSK9 46L allele is more frequent in healthy U.K. men than in FH patients and is strongly associated with a protective plasma lipid profile risk for CHD. Its low frequency (approx. 2% carriers) means that it does not make a major contribution to determining population CHD risk in the U.K.     

Cardiovascular risk factors and endothelial dysfunction

Endothelial dysfunction is a feature of atherosclerosis and is associated with CHD (coronary heart disease) risk factors. This study aimed to determine the relationship between the degree of endothelial dysfunction and calculated cardiovascular risk. Endothelial function, as determined by the ACh/NP (acetycholine/sodium nitroprusside response) ratio on brachial plethysmography, was compared with cardiovascular risk as calculated from the Framingham, PROCAM (Prospective Cardiovascular Munster) and MRFIT (Multiple Risk Factor Intervention Trial) algorithms in 246 (187 male) patients, including 44 (22%) with established CHD. Endothelial dysfunction correlated with the total number of risk factors (r2=0.22; P=0.002) and was related to LDL (low-density lipoprotein)-cholesterol in men and triacylglycerols (triglycerides) in women. The ACh/NP ratio correlated with the occurrence of diabetes, CHD and the LDL-cholesterol concentration (r2=0.58; P<0.001). Endothelial dysfunction was associated with presence of CHD on receiver-operating characteristic plot analysis (area=0.706+/-0.04; P=0.001). There was no correlation between ACh/NP ratio and CHD risk calculated with the Framingham algorithm in men, although both ACh and NP response correlated separately with risk in women. The endothelial ACh/NP ratio correlated with absolute risk in the PROCAM algorithm (r2=0.41; P<0.005). Intermediate results were obtained with MRFIT. Individual risk factors make different contributions to endothelial dysfunction compared with their role in risk calculators. The stronger relationship of endothelial dysfunction with PROCAM risk reflects the contribution of male sex, LDL-cholesterol and triacylglycerols to risk calculated by this algorithm.     

Prediction of coronary risk for primary prevention of coronary heart disease: a comparison of methods

Most recent guidelines advise targeting of lipid lowering for primary prevention at those at high absolute coronary (CHD) risk. We compared the accuracy of five CHD risk assessment methods in identifying such patients: one based on total cholesterol > or = 6.5 mmol/l plus two risk factors, and four based on the Framingham risk function (the European Task Force chart and Sheffield table, both using total cholesterol and the New Zealand chart and modified Sheffield table, both using total: HDL cholesterol ratio) for predicting CHD event risk > or = 2% per year, calculated by an independent risk function, PROCAM, in 126 treated hypertensive men. Cholesterol threshold plus two risk factors had sensitivity 59% and specificity 63%, did not identify some very high-risk patients, and identified very low-risk patients. Framingham-based methods using total cholesterol alone had sensitivity 90-98% and specificity 37-43%, and identified high-risk patients well, but identified some patients at very low risk. Methods based on total: HDL cholesterol ratio had sensitivity 90-98% and specificity 60-63%, and did not identify incorrectly patients at very low CHD risk. Methods based on cholesterol threshold and counting of risk factors are too inaccurate for targeting drug therapy for primary prevention of CHD. Framingham-based methods should incorporate HDL-cholesterol as the total: HDL cholesterol ratio.     

Apolipoprotein(a) size and lipoprotein(a) concentration and future risk of angina pectoris with evidence of severe coronary atherosclerosis in men: The Physicians' Health Study

BACKGROUND: The relationship of lipoprotein (a) [Lp(a)] concentrations with risk of coronary heart disease needs clarification, especially for threshold values for increased risk and for possible interactions with LDL-cholesterol concentrations and apolipoprotein (a) [apo(a)] size polymorphism. This study was designed to examine the ability of baseline Lp(a) concentration and apo(a) size to predict future severe angina pectoris in apparently healthy men. METHODS: Baseline Lp(a) concentration and apo(a) size were determined in 195 men who subsequently developed angina and in 195 men who remained free of cardiovascular disease for 5 years. RESULTS: Cases had higher median Lp(a) concentrations than did controls (30.6 vs 22.5 nmol/L; P = 0.02). Lp(a) concentration was predictive of angina [relative risk (RR) from lowest to highest quintiles: 1.0, 1.5, 1.0, 1.8, and 2.6; P for trend = 0.015]. The increased risk was approximately 4-fold (95% confidence interval, 1.4- to 11-fold) among men who had Lp(a) above the 95th percentile (>158 nmol/L). Men with Lp(a) concentrations in the highest quintile and LDL-cholesterol concentrations >1600 mg/L had a 12-fold increased risk (95% confidence interval, 1.5- to 43-fold). Small apo(a) size isoforms also significantly predicted risk of angina (RR for lowest quintile = 4.1; P for trend = 0.004). When the independent effect of Lp(a) concentration and apo(a) size was assessed by including them in the same multivariate model, only the association between apo(a) size and risk remained significant. CONCLUSIONS: High Lp(a) predicts risk of angina, and the risk is substantially increased with high concomitant LDL-cholesterol. Small apo(a) size predicts angina with greater strength and independence than Lp(a) concentration.     

Elevated remnant-like particle cholesterol and triglyceride levels in diabetic men and women in the Framingham Offspring Study

OBJECTIVE: Remnants of triglyceride-rich lipoproteins are thought to be atherogenic. A new antibody-based assay allows for the isolation of remnant-like particles (RLPs) from plasma or serum, and the subsequent measurement of RLP cholesterol (RLPC) and triglycerides (RLPTGs). We hypothesized that diabetic patients would have higher remnant levels than nondiabetic patients. DESIGN AND METHODS: We compared RLPC and RLPTG levels of diabetic subjects (68 women, 121 men) participating in the Framingham Heart Study with those of nondiabetic subjects (1,499 women, 1,357 men). RESULTS: Mean RLPC values for diabetic women were 106% higher than those for nondiabetic women (0.367 +/- 0.546 mmol/l [14.2 +/- 21.1 mg/dl] vs. 0.179 +/- 0.109 mmol/l [6.9 +/- 4.2 mg/dl]; P < 0.0001), and RLPTG values for diabetic women were 385% higher than those for nondiabetic women (1.089 +/- 2.775 mmol/l [93.1 +/- 245.6 mg/dl] vs. 0.217 +/- 0.235 mmol/l [19.2 +/- 20.8 mg/dl]; P < 0.0001). Similar but less striking differences were observed in diabetic men, who had mean RLPC values 28% higher than those seen in nondiabetic men (0.285 +/- 0.261 mmol/l [11.0 +/- 10.1 mg/dl] vs. 0.223 +/- 0.163 mmol/l [8.6 +/- 6.3 mg/dl]; P < 0.001) and mean RLPTG values 70% higher than those seen in nondiabetic men (0.606 +/- 1.019 mmol/l [53.6 +/- 90.2 mg/dl] vs. 0.357 +/- 0.546 mmol/l [31.6 +/- 48.3 mg/dl]; P < 0.001). Moreover, diabetic men and women had significantly higher total triglycerides and lower HDL cholesterol levels than nondiabetic subjects. CONCLUSIONS: The data indicate that RLP particles are elevated in diabetic subjects. To achieve optimal reduction of risk for cardiovascular disease, treatment of elevated RLP values, along with the control of LDL cholesterol levels, should be considered.     

48例冠心病患者血脂测定临床分析

目的调查冠心病(CHD)患者血脂代谢状况,探讨血脂变化在触发CHD发生发展中的作用及临床意义。方法用日立7020全自动生化分析仪检测48例CHD患者和50例健康对照者血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和脂蛋白(a)[Lp(a)]水平。TC、TG测定采用氧化酶法,HDL-C、LDL-C测定采用直接法,Lp(a)测定采用胶乳增强免疫比浊法。结果 CHD患者TC(5.28±1.07)mmol/L、TG(1.83±0.60)mmol/L、LDL-C(3.41±1.29)mmol/L、Lp(a)(269±170)mg/L,明显比对照组[(4.25±0.93)mmol/L、(1.30±0.43)mmol/L、(2.51±0.87)mmol/L、(138±96)mg/L]高,差异有统计学意义(P0.001);而CHD患者HDL-C[(1.15±0.34)mmol/L]却比对照组[(1.32±0.43)mmol/L]低,差异也有统计学意义(P0.05)。结论 CHD患者存在不同程度的血脂代谢紊乱,TC、TG、LDL-C升高和HDL-C降低将触发CHD的发生和发展。     

Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity

BACKGROUND: Dyslipidaemia may account for increased risk of cardiovascular disease in central obesity. Pharmacotherapy is often indicated in these patients, but the optimal approach remains unclear. We investigated the effects of atorvastatin and fish oil on plasma lipid and lipoprotein levels, including remnant-like particle-cholesterol and apolipoprotein C-III, in dyslipidaemic men with visceral obesity. METHODS: We carried out a 6-week randomized, placebo-controlled, 2 x 2 factorial intervention study of atorvastatin (40 mg day(-1)) and fish oil (4 g day(-1)) on plasma lipids and lipoproteins in 52 obese men (age 53 +/- 1 years, BMI 33.7 +/- 0.55 kg m(-2)) with dyslipidaemia and insulin resistance. Treatment effects were analysed by general linear modelling. RESULTS: Atorvastatin had significant main effects in decreasing triglycerides (-0.38 +/- 0.02 mmol L(-1), P = 0.002), total cholesterol (-1.89 +/- 0.17 mmol L(-1), P = 0.001), LDL-cholesterol (-1.78 +/- 0.14 mmol L(-1), P = 0.001), remnant-like particle-cholesterol (-0.08 +/- 0.04 mmol L(-1), P = 0.035), apolipoprotein B (-49 +/- 4 mg dL(-1), P = 0.001), apolipoprotein C-III (-12.6 +/- 6.1 mg L(-1), P = 0.044) and in increasing HDL-cholesterol (+0.10 +/0- 0.04 mmol L(-1), P = 0.007). Fish oil had significant main effects in decreasing triglycerides (-0.38 +/- 0.11 mmol L(-1), P = 0.002) and in increasing HDL-cholesterol (+0.07 +/- 0.04 mmol L(-1), P = 0.041). There were no significant changes in weight or insulin resistance during the study. CONCLUSIONS: Atorvastatin and fish oil have independent and additive effects in correcting dyslipidaemia in viscerally obese men. Improvement in abnormalities in remnant lipoproteins may occur only with use of atorvastatin. Combination treatment with statin and fish oil may, however, offer an optimal therapeutic approach for globally correcting dyslipidaemia in obesity.     

Increased carotid intima-media thickness in men born in east Finland: a twin study of the effects of birthplace and migration to Sweden on subclinical atherosclerosis

BACKGROUND: There is a clear east-west difference in coronary heart disease (CHD) mortality and incidence in Finland, people living in east Finland having higher CHD rate. A study of Finnish immigrants to Sweden has suggested that a long stay in Sweden would be associated with reduced CHD risk. AIM: To determine whether structural and functional markers of subclinical atherosclerosis differ between men originating from east and west Finland, and whether migration to Sweden influences subclinical atherosclerosis. METHOD: Carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) with high-resolution ultrasound and a set of cardiovascular risk factors were measured in 76 middle-aged male twin pairs (55 pairs from east and 21 pairs from west Finland) discordant for migration to Sweden. RESULTS: Among men living in Finland, IMT was significantly higher in men originating from east Finland compared to those from west Finland (0.796 +/- 0.212 versus 0.704 +/- 0.123 mm, P = 0.02). A similar east-west difference was observed in men who had migrated to Sweden (0.766 +/- 0.220 versus 0.686 +/- 0.089 mm, P = 0.03). The east-west difference in IMT persisted after adjustment for the major traditional cardiovascular risk factors. No east-west difference was seen in FMD. Smoking, Framingham risk score and physical activity had a greater impact on IMT in men originating from east compared to west Finland. CONCLUSIONS: Men originating from east Finland, irrespective of their current residence, have a greater degree of subclinical atherosclerosis and they may be more susceptible to the impact of conventional cardiovascular risk factors than men originating from west Finland.     

Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease.

Elevated lipoprotein(a) (Lp[a]) concentrations are associated with premature coronary heart disease (CHD). In the general population, Lp(a) levels are largely determined by alleles at the hypervariable apolipoprotein(a) (apo[a]) gene locus, but other genetic and environmental factors also affect plasma Lp(a) levels. In addition, Lp(a) has been hypothesized to be an acute phase protein. It is therefore unclear whether the association of Lp(a) concentrations with CHD is primary in nature. We have analyzed apo(a) phenotypes, Lp(a) levels, total cholesterol, and HDL-cholesterol in patients with CHD, and in controls from the general population. Both samples were Chinese individuals residing in Singapore. Lp(a) concentrations were significantly higher in the patients than in the population (mean 20.7 +/- 23.9 mg/dl vs 8.9 +/- 12.9 mg/dl). Apo(a) isoforms associated with high Lp(a) levels (B, S1, S2) were significantly more frequent in the CHD patients than in the population sample (15.9% vs 8.5%, P less than 0.01). Higher Lp(a) concentrations in the patients were in part explained by this difference in apo(a) allele frequencies. Results from stepwise logistic regression analysis indicate that apo(a) type was a significant predictor of CHD, independent of total cholesterol and HDL cholesterol, but not independent of Lp(a) levels. The data demonstrate that alleles at the apo(a) locus determine the risk for CHD through their effects on Lp(a) levels, and firmly establish the role of Lp(a) as a primary genetic risk factor for CHD.     

Dietary fat predicts coronary heart disease events in subjects with type 2 diabetes

OBJECTIVE: To investigate whether quantity or quality of dietary fat predicts coronary heart disease (CHD) events in middle-aged type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: The dietary habits of 366 type 2 diabetic men and 295 women, aged 45-64 years and free from CHD, were assessed with a 53-item food frequency questionnaire. They were followed up for 7 years. RESULTS: Men in the highest tertile of the polyunsaturated/saturated fat (P/S) ratio (>0.28) had a significantly lower risk for CHD death than men in the two lowest tertiles (5.0 vs. 14.2%, P = 0.009). The risk for all CHD events was 14.2 vs. 23.2%, respectively (P = 0.044). P/S ratio did not predict CHD events in women. In Cox multiple regression analyses taking into account other cardiovascular risk factors, the highest P/S ratio tertile was associated with the lowest rate of CHD death in men (P = 0.048). CONCLUSIONS: Low P/S ratio in men predicted future CHD events in type 2 diabetic subjects independently of conventional CHD risk factors.     

Lipoprotein(a) is an independent risk factor for peripheral arterial disease in Chinese type 2 diabetic patients in Taiwan

OBJECTIVE: To examine the association between lipoprotein(a) [Lp(a)] and peripheral arterial disease (PAD) and determine the optimal cutoff in Chinese type 2 diabetic patients in Taiwan. RESEARCH DESIGN AND METHODS: Serum Lp(a) was determined in 557 type 2 diabetic patients (243 men and 314 women) recruited consecutively from a diabetes clinic at the National Taiwan University Hospital. Ankle-brachial index (ABI) <0.9 was diagnosed as PAD (n = 45) and <0.8 as severe PAD (n = 20). Potential confounders included age, sex, BMI, waist-to-hip ratio (WHR), diabetes duration, insulin usage, smoking, hypertension, systolic and diastolic blood pressure, fasting plasma glucose (FPG), total cholesterol, triglycerides, and HDL and LDL cholesterol. RESULTS: The distribution of Lp(a) was right skewed and no significant differences for sex, WHR, insulin usage, smoking, hypertension, and systolic and diastolic blood pressure were observed. In men, log[Lp(a)] was correlated positively with age, duration, and total and LDL cholesterol (borderline significant, P < 0.1) and negatively with BMI, triglycerides, and FPG (P < 0.1). In women, log[Lp(a)] was correlated positively with total and LDL cholesterol and negatively with triglycerides and BMI (P < 0.1). ABI was significantly correlated with log[Lp(a)], especially in men or in patients with PAD. The optimal cutoff determined by discriminant analysis was 13.3 mg/dl. Patients with Lp(a) above this value had a 2.7-fold higher risk of PAD after multivariate adjustment. Lp(a) also significantly increased from no PAD to mild and severe PAD (17.1 +/- 14.4, 23.7 +/- 20.3, and 36.9 +/- 22.8 mg/dl, respectively, P < 0.001). CONCLUSIONS: Lp(a) is an independent risk factor for PAD in type 2 diabetic patients in Taiwan. The optimal cutoff is 13.3 mg/dl.     

Longitudinal association of glycemia and microalbuminuria: the Framingham Offspring Study

OBJECTIVE: To assess current and long-term associations of glycemia with microalbuminuria, a marker of generalized endothelial injury. RESEARCH DESIGN AND METHODS: We measured clinical characteristics, fasting plasma glucose, and the urinary albumin-to-creatinine ratio (UACR) in 1,311 men and 1,518 women attending the sixth examination cycle (1995-1998) of the Framingham Offspring Study. After excluding participants with diabetes or cardiovascular disease (CVD) at the baseline examination (1971-1974), we used fasting glucose measured at baseline, examination 6, and at least two additional examinations from 1974 to 1995 in regression models to predict risk for microalbuminuria (UACR > or = 30 mg/g) associated with baseline, current, and 24-year time-integrated glycemia. RESULTS: Microalbuminuria was present in 9.5% of men and 13.4% of women. Among men, age-adjusted odds ratios (95% CI) for microalbuminuria associated with each 0.28 mmol/l (5 mg/dl) increase in baseline, current, and time-integrated glucose levels were 1.12 (1.00-1.16), 1.08 (1.05-1.10), and 1.16 (1.11-1.21), respectively. These effects persisted after adjustment for systolic blood pressure and other confounders. Higher glucose levels also predicted incident diabetes and CVD. Mean time-integrated glucose levels were highest among men who developed both CVD and microalbuminuria (SE 6.82 +/- 0.16 mmol/l), intermediate among men with either condition (6.03 +/- 0.65 mmol/l), and lowest among men with neither condition (5.49 +/- 0.02 mmol/l; P < 0.001 for all pairwise comparisons). We observed similar associations in women. CONCLUSIONS: Long-term hyperglycemia and subdiabetic glycemia increase risk for microalbuminuria. Microalbuminuria, type 2 diabetes, and CVD seem to arise together over the course of decades, consistent with the hypothesis that they share a common antecedent.     

The significant effect of diabetes duration on coronary heart disease mortality: the Framingham Heart Study

OBJECTIVE: The risk of coronary heart disease (CHD) in type 2 diabetes is two- to threefold higher than in the general population, but the effect of diabetes duration on CHD risk has not been well characterized. We hypothesized that duration of diabetes is an important predictor of incident CHD among people with diabetes. RESEARCH DESIGN AND METHODS: The duration of diabetes (fasting glucose > or =126 mg/dl, random glucose > or =200 mg/dl, or use of an oral hypoglycemic agent or insulin) was assessed in participants with diabetes in the original and offspring cohorts of the Framingham Heart Study. Only subjects with diabetes diagnosed between the ages of 30 and 74 years, without a history of ketoacidosis, and free of cardiovascular disease at the baseline evaluation were included. Cox proportional hazards models were used to estimate the hazard ratio of incident CHD events and mortality over a 12-year follow-up period; models were adjusted for known CHD risk factors. RESULTS: Among 588 person-exams with diabetes (mean age 58 +/- 9 years, 56% men), there were 86 CHD events, including 36 deaths. After adjustment for age, sex, and CHD risk factors, the risk of CHD was 1.38 times higher for each 10-year increase in duration of diabetes (95% CI 0.99-1.92), and the risk for CHD death was 1.86 times higher (1.17-2.93) for the same increase in duration of diabetes. CONCLUSIONS: Duration of diabetes increases the risk of CHD death independent of coexisting risk factors. Further research is necessary to understand the pathophysiology of this increased risk.     

正常(或低)胆固醇冠心病患者的脂蛋白谱特点

目的研究血清总胆固醇（ＴＣ）正常或低于平均水平的冠心病（ＣＨＤ）患者的脂蛋白谱特点。方法观察诊断明确的男性ＣＨＤ２２５例，以年龄配对、生活水平相似的健康男子２２５例为对照。两组中均排除与脂代谢有关的疾病及用药。对血脂作多指标［１４项，包括载脂蛋白（ａｐｏ）８项］综合分析。结果ＣＨＤ患者中ＴＣ高于５．１７ｍｍｏｌ／Ｌ者１０８例（４８％），低于此水平者１１７例（５２％）。高ＴＣ组的血脂特点以低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）和ａｐｏＢ增高为主，低ＴＣ组（ＴＣ平均４．４１ｍｍｏｌ／Ｌ，相应的对照组为４．８１ｍｍｏｌ／Ｌ）的特点是高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）及其亚类明显偏低，尤以ａｐｏＡＩ低下最明显。多数ＨＤＬ－Ｃ低的病例并无甘油三酯增高，部分病例以低ＨＤＬ（包括ＨＤＬ－Ｃ，ａｐｏＡＩ、ＡＩ）为单一的血脂异常。逐步回归分析优选判断ＣＨＤ的指标，在低ＴＣ组首选是ａｐｏＡＩ，其次为脂蛋白（ａ）；但高ＴＣ组以ａｐｏＢ为首选。结论低ＴＣ组在ＬＤＬ致动脉硬化作用明显减弱的情况下，低ＨＤＬ成为主要的（独立的）脂类危险因素     

Cardiovascular risk factors in hemodialysis and peritoneal dialysis patients

BACKGROUND. Cardiovascular disease (CVD) is the major cause of mortality and morbidity of hemodialysis (HD) and peritoneal dialysis (CAPD) patients. We aimed to investigate the cardiovascular risk factors and their correlation with CVD in groups of HD and CAPD patients. METHODS. Thirty HD patients, 30 CAPD patients and 30 healthy controls were included in the study. Apolipoprotein A-l (apo A-l), apolipoprotein B (apo B), apolipoprotein(a) [Lp(a)] and high-sensitivity CRP (hs-CRP) were measured with a Beckman Coulter nephelometer, and homocysteine (Hcy) was determined with an Agilent HPLC analyzer. Lipid profile was determined with a Synchron LX 20 Pro analyzer. RESULTS. Hcy levels were 41.9+/-19.4, 41.8+/-38.5 and 9.3+/-3.5 micromol/L; Lp(a) levels were 325+/-315, 431+/-367 and 130+/-97 mg/L; hs-CRP levels were 3.78+/-3.21, 4.34+/-3.39 and 2.07+/-1.67 mg/L; apo A1/apo B ratios were 1.46+/-0.6, 1.36+/-0.5 and 1.80+/-0.59; total cholesterol levels were 3.56+/-0.7, 4.84+/-1.1 and 4.39+/-0.5 mmol/L; triglycerides were 1.44+/-0.5, 1.60+/-0.8 and 0.85+/-0.5 mmol/L in the HD, CAPD and control groups, respectively. CONCLUSION. HD and CAPD patients had higher Hcy, hs-CRP and Lp(a) levels and lower apo A/B ratios than controls. There was no significant difference between the HD and CAPD groups. Hypertension, age and hs-CRP showed a positive correlation with CVD.