Serum osteoprotegerin is a predictor for incident cardiovascular disease and mortality in a general population: the Tromsø Study

Summary. Background: Osteoprotegerin (OPG) concentration in serum is associated with the presence and severity of atherosclerosis. Objective: To investigate the association between serum osteoprotegerin and the risk of a future myocardial infarction, ischemic stroke and mortality in a general population. Patients/methods: OPG was measured in serum collected from 6265 subjects recruited from a general population without a prior myocardial infarction and ischemic stroke (the Tromsø Study). Incident myocardial infarction, ischemic stroke and mortality were registered during follow‐up. Cox regression models were used to estimate crude and adjusted hazard ratios and 95% confidence intervals (HR; 95% CI). Results: There were 575 myocardial infarctions, 284 ischemic strokes and 824 deaths (146 deaths as a result of ischemic heart disease, 78 deaths because of stroke and 600 deaths due to other causes) in the cohort during a median of 10.6 years of follow‐up. Serum OPG (per SD [1.13 ng mL^?1] increase in OPG) was associated with an increased risk of a myocardial infarction (1.20; 1.11–1.31), ischemic stroke (1.32; 1.18–1.47), total mortality (1.34; 1.26–1.42), death because of ischemic heart disease, (1.35; 1.18–1.54), stroke (1.44; 1.19–1.75) and non‐vascular causes (1.31; 1.22–1.41) after adjustment for age, gender, current smoking, systolic blood pressure, body mass index, high density lipoprotein cholesterol, total cholesterol, creatinine, high sensitivity C‐reactive protein (CRP) and diabetes mellitus or HbA1c > 6.1%. No association was detected between OPG and incident hemorrhagic stroke (1.02; 0.73–1.43). Conclusions: Serum OPG was associated with future risk of myocardial infarction, ischemic stroke, total mortality, mortality of ischemic heart disease, stroke and of non‐vascular causes independent of traditional cardiovascular risk factors.     

Association of blood pressure components with mortality and cardiovascular events in prehypertensive individuals: a nationwide population-based cohort study

Background: The effects of each blood pressure index [systolic and diastolic blood pressure (SBP, DBP), pulse pressure (PP), mean arterial pressure (MAP)] on the occurrence of mortality and cardiovascular (CV) events have not yet been investigated in prehypertensive populations.

Methods: A total of 30,258 prehypertensive Korean participants underwent periodic health examination between 2003 and 2004 were enrolled, and the associations of BP components with mortality and CV events were investigated. Moreover, based on the DBP [80 ≤ DBP <90?mmHg (N?=?21,323) and DBP <80?mmHg (N?=?8,935)], the effects of BP components were also evaluated.

Results: Multivariate Cox analyses in prehypertensive group revealed that the hazard ratios (HRs) were 1.121 and 1.130 per 10?mmHg increase in SBP and PP for mortality, respectively. Additionally, 10?mmHg increase of SBP (HR:1.090) was still significantly, but increase of PP (HR:1.060) was marginally associated with higher incidence of CV events. However, there were no significant associations with increase in DBP or MAP on adverse clinical outcomes in prehypertensive group. In the prehypertensive subjects with DBP <80?mmHg, CV events more frequently occurred by 38.8% and 28.5% per 10?mmHg increase in SBP and PP, respectively.

Conclusions: Prehypertensive subjects might need to be cautioned when they have high SBP or PP with low DBP even in healthy populations.

• Key message

• Prehypertensive subjects should be cautioned when they have high-systolic blood pressure or pulse pressure with low-diastolic blood pressure, even without previous hypertension, diabetes mellitus or chronic kidney disease.

     

斑点追踪技术预测急性心肌梗死患者再发心血管事件及死亡风险的随访研究

目的：应用斑点追踪显像(STI)技术分析急性心肌梗死(AMI)患者的心功能,并通过长期随访,探讨左室运动功能的受损程度及特点判断 AMI患者预后的临床意义。方法采集78例首发 AMI患者入院时左心超声图像,分析得出左室纵向峰值应变(LPSS)、径向峰值应变(RPSS)及环向峰值应变(CPSS),结合长期临床随访资料评价患者 AMI后再发心血管事件及心因性死亡的风险。结果与随访期间未发生心血管事件的 AMI患者相比,再发心血管事件患者 LPSS和 CPSS均相对较低(P <0.001),其中CPSS对患者再发心血管事件风险的预测相对较好(HR=1.4096)。在对患者死亡风险的预测中,LPSS的预测价值相对较高(P <0.001,HR=1.5735)。结论 STI 对判断 AMI 患者再发心血管事件以及心因性死亡的风险具有优势,CPSS及 LPSS分别是预测再发心血管事件及死亡的有效指标。     

Genetic determinants of von Willebrand factor levels and activity in relation to the risk of cardiovascular disease: a review

Summary. It is well established that high plasma von Willebrand factor (VWF) levels are associated with an increased risk of arterial thrombosis, including myocardial infarction and ischemic stroke. As plasma VWF levels are, to a large extent, genetically determined, numerous association studies have been performed to assess the effect of genetic variability in the VWF gene (VWF) on VWF antigen and activity levels, and on the risk of arterial thrombosis. Genetic variations in other regulators of VWF, including the ABO blood group, ADAMTS‐13, thrombospondin‐1 and the recently identified SNARE protein genes, have also been investigated. In this article, we review the current literature as exploring the associations between genetic variations and the risk of arterial thrombosis may help elucidate the role of VWF in the pathogenesis of arterial thrombosis. However, as studies frequently differ in design, population and endpoint, and are often underpowered, it remains unclear whether VWF is causally related to the occurrence of arterial thrombosis or primarily mirrors endothelial dysfunction, which predisposes to atherosclerosis and subsequent arterial thrombosis. Nevertheless, current studies provide interesting results that do not exclude the possibility of VWF as causal mediator and justify further research into the relationship between VWF and arterial thrombosis. Large prospective studies are required to further establish the role of VWF in the occurrence of arterial thrombosis.     

Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet,Cancer and Health cohort study

Summary. Background: The presence of vascular disease (peripheral artery disease [PAD] and/or myocardial infarction [MI]) may impact on the risk of stroke and death among patients with incident atrial fibrillation (AF). To test this hypothesis, we analyzed data from a large Danish prospective cohort, the Danish Diet, Cancer and Health (DCH) study, to assess the risk of stroke or death among those who developed AF according to concomitant presence of vascular disease. Methods: A prospective cohort study of 57 053 persons (27 178 men and 29 876 women, respectively), aged between 50 and 64 years. The risk of stroke or death for patients with vascular disease was assessed amongst 3315 patients with incident AF (mean age, 67.1 years; 2130 men, 1185 women) using Cox proportional hazard models, after a median follow‐up of 4.8 years. Results: Of the subjects with AF, 417 (12.6%) had ‘vascular disease’ (PAD and/or prior MI). The risk of the primary endpoint (stroke or death) was significantly higher in patients with vascular disease at 1‐year follow‐up (crude hazard ratio [HR] 2.51 [1.91–3.29]), with corresponding crude HRs for PAD and MI being 3.51 (2.40–5.13), and 1.99 (1.46–2.72), respectively. For the secondary endpoints of death or stroke individually, these risk estimates were similar (crude HR 2.48 [1.89–3.26] and 1.77 [1.18–2.66], respectively). After adjustment for risk factors within the CHADS₂ score, the adjusted HR for the primary endpoint (stroke or death) in patients with vascular disease was 1.91 (1.44–2.54), which was also significant for death (1.97 [1.48–2.62]). Conclusion: Vascular disease (prior MI and PAD) is an independent risk factor for the primary endpoint of ‘stroke or death’ in patients with AF, even after adjustment for the CHADS₂ risk score, although this is driven by the impact on mortality. This reaffirms that patients with vascular disease represent a ‘high‐risk’ population, which necessitates proactive management of all cardiovascular risk factors and effective thromboprophylaxis (i.e. oral anticoagulation), which has been shown to significantly reduce the risk of stroke and death in AF.     

High blood hemoglobin concentration as risk factor of major atherosclerotic cardiovascular events in 114,159 healthy men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

Abstract

Background. Few studies have tested differences in relationships between hemoglobin (Hb) and long-term risk of major cardiovascular diseases according to age and gender in healthy subjects as opposed to anemia.

Aims. Such relationships were examined and risk-tested in relation to Hb values in the Apolipoprotein MOrtality RISk (AMORIS) Study.

Methods. Using data from AMORIS and the Swedish hospital discharge and mortality registers, a prospective cohort study of 114,159 subjects with mean follow-up of 11.8 years, the association between Hb and risk of acute myocardial infarction (AMI), ischemic stroke (IS), and congestive heart failure (CHF) by Cox regression analysis according to age and gender was studied.

Results. Elevated Hb levels were associated to acute myocardial infarction (AMI) (HR 1.10 (1.06–1.13) per SD change), mostly confined to men and younger subjects but with greater sex similarity trends for CHF. Slightly increased risks were seen for the lowest Hb levels in the elderly and in females. IS risk was positively and more linearly associated to Hb.

Interpretation. In AMORIS the highest AMI and CHF risks were found in the upper region of the distribution, but different shapes of relationships according to age and gender were found. IS associated positively with Hb. Key words:     

Prospective study of circulating soluble CD40 ligand concentrations and the incidence of cardiovascular disease in a nested prospective case–control study of older men and women

Summary. Background: CD40 ligand(CD40L) is implicated in atherosclerotic plaque formation. Objectives: We investigated prospective associations between circulating soluble CD40L and myocardial infraction (MI) or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors. Methods: Baseline serum CD40L (sCD40L) was measured in incident MI (n = 368) and stroke (n = 304) cases and two controls per case, ‘nested’ in prospective UK studies of 4252 men and 4286 women aged 60–79 years, sampled from general practices in Britain in 1998–2000, with 7‐year follow‐up for fatal and non‐fatal MI and stroke. Results: sCD40L was higher in smokers and negatively associated with lung function and positively associated with total cholesterol and markers of inflammation, but not with other established cardiovascular disease (CVD) risk factors. Geometric mean sCD40L levels did not differ between MI cases and controls (5.94 ng mL^?1 vs. 5.82 ng mL^?1; P = 0.5) or between stroke cases and controls (5.61 ng mL^?1 vs. 5.28 ng mL^?1, P = 0.1). There was no strong evidence for elevated risk of MI or stroke in multivariable models comparing participants in the top to those in the bottom third of sCD40L. Age‐adjusted odds ratios (ORs) were 1.39 [95% confidence interval (CI) 0.98, 1.96] for MI and 1.16 (0.78, 1.73) for stroke. These attenuated to 1.24 (95% CI 0.86, 1.79) and 1.18 (0.78, 1.78), respectively, after adjustment for established and novel CVD risk factors. Conclusions: sCD40L is associated with other inflammatory markers but is not itself a strong independent risk marker for either stroke or MI.