Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

OBJECTIVE: Based on case-control and prospective studies elevated blood total homocysteine (tHcy) has been suggested to be an independent risk factor for cardiovascular diseases (CVD). The purpose of the study was to explore the joint effect of increased serum tHcy concentration and other risk factors on the risk of CVD mortality in middle-aged men without a history of heart disease or stroke. DESIGN: A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. SETTING: Eastern Finland. Subjects. A total of 802 men aged 46-64 years, examined in 1991-93. MAIN OUTCOME MEASURES: CVD mortality event. RESULTS: The mean serum tHcy concentration was 10.8 micromol L(-1) (SD 3.3). During the average follow-up time of 10.8 years 50 men experienced a CVD death. The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02-3.19) in men in the highest serum tHcy third versus lower thirds after adjustment for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration appeared to increase the risk of CVD death in men who smoke or who have high circulating concentrations of serum total or LDL cholesterol, apo-B apolipoprotein or plasma fibrinogen. CONCLUSION: We conclude that homocysteine may increase the risk of CVD mortality in middle-aged men from Eastern Finland, and it may especially increase the risk when present with other risk factors for CVD.     

The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.     

同型半胱氨酸与缺血性卒中的预防

来自流行病学和观察性研究的证据支持,同型半胱氨酸为缺血性卒中的重要危险因素,采用叶酸和维生素B类降低同型半胱氨酸可有效预防缺血性卒中.但是,绝大多数临床试验得出的结果 却为阴性.文章对此进行了分析.     

Homocysteine and cardiovascular disease: current evidence and future prospects

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Despite the well-known effectiveness of vitamin supplementation in reducing homocysteine levels, it is not known whether lowering of homocysteine levels is associated with a reduction in cardiovascular morbidity and mortality. The aim of this review is to discuss the epidemiologic evidence about the relation between homocysteine and cardiovascular disease, the pathophysiologic mechanisms responsible for the deleterious vascular and hemostatic effects of homocysteine, and studies of the potential benefits of homocysteine-lowering therapy.     

同型半胱氨酸调控miRNA在心血管疾病中的作用研究进展

同型半胱氨酸(Hcy)是由蛋氨酸代谢生成的中间代谢产物,大量研究发现Hcy与心血管疾病有很大关系。微小RNA(miRNA)是一大类短链非编码RNA,已在多种疾病中证实miRNA失调可导致疾病的发生发展,比如免疫紊乱、糖尿病、癫痫、癌症等。目前miRNA因其在心血管系统中的关键作用而被认为是心血管疾病的新治疗策略。当前研究已证实Hcy与miRNA均是心血管疾病的危险因素,Hcy可通过调控miRNA影响心血管疾病,miRNA也可能对Hcy引起相应变化。但Hcy与miRNA的相互影响在心血管疾病中的作用还有待明确。本文简要综述了Hcy调控miRNA在心血管疾病中的作用进展及其潜在的临床应用价值。     

同型半胱氨酸与糖尿病及心脑血管疾病关系

流行病学资料表明,高同型半胱氨酸血症与糖尿病及心脑血管疾病关系密切;但大型临床试验却显示降低血同型半胱氨酸浓度的治疗对这些疾病无益。文章对已有的资料进行综述,探讨同型半胱氨酸与糖尿病及心脑血管疾病的关系,以期对临床及今后的研究提供线索。     

Risk Factor Clusters and Cardiovascular Disease in High-Risk Patients: The UCC-SMART Study

Background:Clustering of vascular risk factors, i.e., the co-existence of two or more risk factors, has been associated with a higher risk of cardiovascular disease (CVD) in the general population. This study aims to firstly, examine patterns of clustering of major cardiovascular risk factors in high-risk patients and their relation with the risk of recurrent cardiovascular disease and all-cause mortality. Secondly, to assess which combinations are associated with the highest risk of CVD and all-cause mortality and to study population attributable fractions.Methods:A total of 12,616 patients from the Utrecht Cardiovascular Cohort – Second Manifestations of ARTerial diseases (UCC-SMART) study consisting of patients with or a high risk to develop cardiovascular disease were studied. We constructed sixteen clusters based on four individual modifiable risk factors (hypertension, dyslipidemia, current smoking, overweight). Patients were followed from September 1997 to March 2017. Cox proportional hazard models were used to compute adjusted hazard ratios for CVD risk and all-cause mortality and 95% confidence intervals for clusters, with patients without any risk factor as reference group. The population attributable fractions (PAFs) were calculated. Subgroup analyses were conducted by age and sex.Results:During a mean follow-up period of 8.0 years, 1836 CVD events were registered. The prevalence of patients with zero, one, two, three, and four risk factors was 1.4, 11.4, 32.0, 44.8 and 10.4%. The corresponding hazard ratios (HR) for CVD risk and all-cause mortality were 1.65 (95% CI 0.77; 3.54) for one risk factor, 2.61 (1.24; 5.50) for two, 3.25 (1.55; 6.84) for three, and 3.74 (1.77; 7.93) for four risk factors, with patients without any risk factor as reference group. The PAFs were 6.9, 34.0, 50.1 and 22.2%, respectively. The smoking-hypertension-dyslipidemia combination was associated with the highest HR: 4.06 (1.91; 8.63) and the hypertension-dyslipidemia combination with the highest PAF: 37.1%.Conclusion:Clusters including smoking and hypertension contributed to the highest risk of CVD and all-cause mortality. This study confirms that risk factor clustering is common among patients at high-risk for CVD and is associated with an increased risk of CVD and all-cause mortality.     

心血管疾病剩余风险研究新进展

目前,心血管内科医师预防冠心病等心血管疾病的主要方式包括:调整生活方式、控制血压血耱及调节低密度脂蛋白胆固醇等.然而,在临床实践中,即使上述主要危险因素得到很好防治,也未能完全控制心血管疾病的发生发展,主要原因在于存在心血管疾病剩余风险.在临床实践中,我们除了要重视主要危险因素,也要对剩余危险因素进行预防治疗,这样我们才可能从根本上解决心血管疾病的防治问题,现就心血管疾病剩余风险综述如下.     

类风湿关节炎患者血清同型半胱氨酸和脂联素的表达及其意义

目的探讨类风湿关节炎(RA)患者血清同型半胱氨酸(HCY)、脂联素(ADP)水平的变化及其意义。方法采用酶联免疫吸附试验(ELISA)法检测RA患者治疗前后血清HCY、ADP水平,并与正常对照组及糖尿病对照组比较。结果 RA组血清HCY水平为(6.63±2.75)μmol/L,显著高于正常对照组(4.30±2.12)μmol/L(P=0.003),与糖尿病组(6.69±2.98)μmol/L比较差异无统计学意义(P>0.05);RA组血清ADP水平为(208.12±74.06)μg/L,低于正常对照组(241.73±82.05)μg/L,高于糖尿病对照组(195.95±62.03)μg/L,3组间差异无统计学意义(P>0.05)。治疗6个月后,RA组应用甲氨蝶呤者血清HCY水平显著升高,(7.74±3.07)μmol/Lvs(6.84±3.15)μmol/L,P=0.007;应用来氟米特者血清HCY水平无显著变化,(6.37±2.22)μmol/Lvs(6.43±2.38)μmol/L,P=0.739。结论 RA患者血清HCY水平升高,甲氨蝶呤治疗后进一步升高;血清ADP水平无明显变化。RA患者发生心血管疾病风险升高。     

Metabolism of Homocysteine and its Relationship with Cardiovascular Disease

Hyperhomocysteinemia, or the rise of plasmatic homocysteine levels above 15 g/dL, is accepted nowadays as an independent risk factor for cardiovascular disease in men and women. Homocysteine (Hcy) is a non-protein forming aminoacid (aa) derivated from the loss of the methyl group, found within methionine. Methionine regenerates by retrieving the methyl radical from 5-methyltetrahydrofolate (5-MTHF) creating tetrahydrofolate (THF) which will then regenerate to 5-MTHF through the action of methylentetrahydrofolate reductase (MTHFR). This process is called remethylation. Alternatively, Hcy can follow the transsulfuration route, where through cystationine--syntetase (CBS), it irreversibly converted into cystationine, a precursor of cysteine, glutathione, and other substances that are finally excreted in the urine. Hyperhomocysteinemia results from inhibition of the remethylation route, or inhibition or saturation of the transsulfuration pathway. Main factors causally associated increased plasmatic Hcy are mutations of the enzymes MTHFR and CBS; varying nutritional and health states; demographic factors; and, others. The most accepted hypotheses about Hcy action in cardiovascular disease are direct endothelial and vessel wall damage; oxidative stress generation; and, stimulation of a procoagulant and proinflammatory state of blood components. Since hyperhomocysteinemia can be effectively treated with folic acid, prospective trials are underway to determine if folate therapy is required to lower Hcy levels in plasma. These studies also attempt to address the impact, if any, of folate therapy in the reduction of cardiovascular risk, and to demonstrate if hyperhomocysteinemia is actually an independent risk factor that can be effectively treated.     

Effect of statin (HMG-Co-A-Reductase Inhibitor) use on 1-year mortality and hospitalization rates in older patients with cardiovascular disease living in nursing homes

OBJECTIVES: To quantify the effect of statins on 1-year mortality, hospitalizations, and decline in physical function among patients with cardiovascular disease (CVD) aged 65 and older living in nursing homes. DESIGN: Retrospective cohort study. SETTING: All Medicare/Medicaid certified nursing homes (N = 1,492) in Maine, New York, Mississippi, and South Dakota. PARTICIPANTS: We identified 51,559 older patients with CVD from a population database that merged sociodemographic data and functional, clinical, and drug treatments from more than 300,000 newly admitted nursing home residents from 1992 to 1997. Statin users (n = 1,313) were matched with nonusers (n = 1,313) in the same facilities. MEASUREMENTS: All-cause mortality, hospitalization, combined endpoint of mortality or hospitalization, and decline in physical function were determined at 1 year, and survival analysis was performed. RESULTS: Prevalence of statin use in this frail older cohort with CVD was 2.6%. Statin use varied by age, gender, comorbid condition, medication use, and cognitive and physical function. One-year mortality was 229/1,000 person-years in the statin group and 404/1,000 person-years in the nonusers, with an adjusted hazard rate ratio (HRR) of 0.69, 95% confidence interval (CI) = 0.58-0.81. The estimated number needed to treat was seven (95% CI = 5-13). This association with improved all-cause mortality was evident for women and men and for age groups 75 to 84, and 85 and older. CONCLUSION: Statin therapy is associated with improved clinical outcomes, including reduction in 1-year all-cause mortality, and the combined endpoint of death or hospitalization in a frail older population with CVD. Some caution should be taken in interpreting these results because potential bias from residual confounding could affect these results.     

Undertreatment and overtreatment with statins: the Oslo Health Study 2000-2001

OBJECTIVE: We examined the prevalence and factors associated with use of cholesterol-lowering statins in the population. METHODS: Demographic, medical, anthropometric and lifestyle data was obtained from 6233 men and 7521 women born in 1924/25, 1940/41, 1955 and 1960 that participated in the Oslo Health Study 2000-2001. A nonfasting blood sample was collected. RESULTS: Of subjects with a heart attack, angina, stroke or diabetes 45% of men and 35% of women were taking a statin (P < 0.001). Of subjects with cardiovascular disease (CVD) or diabetes taking statins 61% of men and 40% of women achieved total serum cholesterol levels < or =5 mmol L(-1). The odds ratio for taking a statin was increased amongst subjects who also took antihypertensive drug(s) or acetylsalicylic acid, subjects with a family history of coronary heart disease (CHD) and women who had visited the general practitioner within the last year. Amongst presumed healthy subjects use of statins increased from about 1% in women aged 40-45 years, to 7% at age 60 and to 12% at age 75 whilst the corresponding figures for men were 3%, 8% and 9%, respectively. About 22% of men but <2% of women aged 60 who were not taking statins had a 10-year Framingham CHD risk score >20%. Determinants of statin use were similar to those amongst subjects with CVD or diabetes. CONCLUSION: People with CVD or diabetes remain undertreated with statins, women more so than men. Use of other preventive drugs, the family history and recent contact with the general practitioner were the most important determinants of statin use in primary and secondary prevention. Amongst healthy subjects aged 60 or 75 years women received statins disproportionately to their low CHD risk compared with men.     

Follow‐ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007: Levels and 6‐year changes in risk factors

Abstract. Raiko JRH, Viikari JSA, Ilmanen A, Hutri‐Kähönen N, Taittonen L, Jokinen E, Pietikäinen M, Jula A, Loo B.‐M, Marniemi J, Lehtimäki T, Kähönen M, Rönnemaa T, Raitakari OT, Juonala M (University of Turku; University of Tampere and Tampere University Hospital, Tampere; University of Oulu, Oulu; Vaasa Central Hospital, Vaasa; University of Helsinki, Helsinki; and Center of Social and Health Services, Kuopio; Finland). Follow‐ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007: Levels and 6‐year changes in risk factors. J Intern Med 2010; 267 : 370–384. Objectives. To examine cardiovascular risk factor levels in 2007 and their 6‐year changes between 2001 and 2007 using the data collected in the follow‐ups of the Cardiovascular Risk in Young Finns Study. Design. Population‐based follow‐up study. Subjects. A total of 2204 healthy Finnish adults aged 30–45 years (1210 women; 994 men). Main outcome measures. Levels in 2007 and changes between 2001 and 2007 of lipids, insulin, glucose, blood pressure, smoking, body mass index, alcohol consumption, waist and hip circumferences. Results. The mean serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations in 30‐ to 45‐year‐old adults were 5.05, 3.09, 1.34 and 1.40 mmol L^?1, respectively. Significant changes (P < 0.05) between 2001 and 2007 in 30‐ to 39‐year‐old subjects included a decrease in total cholesterol (?6.6% in men, ?5.8% in women), LDL‐cholesterol (?10.2% and ?11.6%) and an increase in diastolic blood pressure (3.5% and 3.9%). Waist circumference (1.8% and 5.5%) and systolic blood pressure increased in 36–39 year olds (2.3% and 2.3%). HDL‐cholesterol increased in 30‐ to 33‐year‐old women (5.8%) Glucose levels increased in 30‐ to 39‐year‐old women (3.7%) and 36‐ to 39‐year‐old men (3.6%). Smoking prevalence decreased in 36‐ to 39‐year‐old men from 29.8% to 22.2%. Conclusions. The 6‐year changes in total cholesterol, LDL‐cholesterol and HDL‐cholesterol in young Finns were favourable between 2001 and 2007. However, waist circumference, glucose and blood pressure levels increased. Therefore, continuous efforts are still needed in fighting against cardiovascular risk factors.