Relation between atherosclerosis risk factors and aspirin resistance in a primary prevention population

Resistance to inhibition of platelet function by aspirin may contribute to future myocardial infarction and stroke. Adverse cardiovascular outcomes have been associated with aspirin resistance on several different platelet function assays, including the level of urinary 11-dehydro thromboxane B2 (Tx-M), platelet aggregation to arachidonic acid and adenosine diphosphate, and closure time on the platelet function analyzer-100. We examined the concordance of these aspirin-resistance assays and their relation to cardiovascular risk factors in a primary prevention population. Asymptomatic patients (n = 1,311) at increased risk for coronary heart disease were evaluated before and after 2 weeks of aspirin (81 mg/day). Aspirin resistance was defined according to published criteria for these 3 assays of platelet function. Subjects were characterized for the presence of atherosclerosis risk factors. Agreement among the 3 assays was poor. Only 5 patients met aggregation criteria for aspirin resistance. Attenuated suppression of urinary Tx-M by aspirin was associated with a greater atherosclerotic risk profile and Framingham risk score in multivariable regression analysis. Aspirin resistance by platelet function analyzer-100 was associated only with increased von Willebrand factor levels and not with atherosclerotic risk profile. In conclusion, in a primary prevention population, different published criteria for aspirin resistance classify distinct groups of patients as aspirin resistant with very little overlap. Higher Tx-M, which reflects decreased suppression of thromboxane production in vivo, is the only criterion associated with atherosclerosis risk factors, suggesting that this measurement may represent the most relevant approach for identifying asymptomatic subjects whose aspirin treatment will "fail."     

颈动脉粥样硬化伴斑块形成的危险因素分析

目的探讨动脉粥样硬化伴斑块形成的相关危险因素。方法随机选取2013-12~2014-12到该院体检的300例体检者,根据颈动脉内膜-中层厚度(IMT)和斑块的形态分为颈动脉粥样硬化伴斑块形成组(斑块组)194例和颈动脉粥样硬化无斑块形成组(无斑块组)106例。每例患者均记录患者的性别、年龄、吸烟指数、饮酒指数、体重指数(BMI)、血压(SBP)、空腹血糖(FBG)、总胆固醇(TC)、低密度脂蛋白(LDL)、脂蛋白a[LP(a)]、血尿酸(UA)、同型半胱氨酸(Hcy)等,以及有无高血压、糖尿病病史,应用SPSS17.0软件对斑块组和非斑块组进行单因素分析及Logistic回归分析,比较其可干预的危险因素(排除性别、年龄、遗传等不可干预的因素)与颈动脉粥样硬化的关联程度。结果两组SBP、FBG、TC、LDL、LP(a)差异有统计学意义(P均0.05);其中影响颈动脉粥样硬化因素LDL(OR=9.392)、FBG(OR=2.328)具有统计学意义(P0.05)。结论颈动脉粥样硬化是多种危险因素共同作用的结果,其中LDL和FBG是预防动脉硬化优先考虑的独立危险可控制因素。     

Effect of carotid atherosclerosis screening on risk stratification during primary cardiovascular disease prevention

We investigated the effect that carotid plaque area (CPA) and intima media thickness (IMT) measurements have on risk stratification in 95 patients with intermediate Framingham scores (6% to 19%). The risk status of each patient was adjusted to be low, intermediate, or high based on the results of carotid ultrasound. After carotid testing, 44% (IMT) and 45% (CPA) of the intermediate-risk patients were stratified as low risk, and 22% (IMT) and 40% (CPA) were stratified as high risk. Using the threshold values derived from our laboratory, 28% (IMT) and 45% (CPA) of patients were stratified as low risk, and 35% (IMT) and 27% (CPA) were identified as high risk. These tests adjust the risk strata of >/=63% of patients deemed as having intermediate risk by Framingham scores.     

White-coat hypertension and carotid artery atherosclerosis: a matching study

BACKGROUND: Blood pressure (BP) measurements obtained in the clinic have long served as the basis for determining risk of hypertensive vascular disease, yet many patients with high BP in the physician's office are normotensive elsewhere. It remains unclear whether such patients with "white coat" hypertension elude the risk of atherosclerosis. METHODS: Community residents 40 to 70 years of age and not receiving any cardiovascular medications were recruited to participate in a study of cardiovascular risk factors. On the basis of clinic and daytime ambulatory BP and a threshold criterion of 140/90 mm Hg, subjects were classified as having persistent hypertension, white-coat hypertension, or persistent normotension. One-to-one matching was conducted in male participants on the basis of race and BP. Subjects with persistent hypertension and white-coat hypertension were matched on clinic BP, and those with white-coat hypertension and normotension were matched on daytime ambulatory BP. RESULTS: The 3 matched groups of men (n=40 in each group) were similar in age, smoking status, and fasting glucose and lipid levels. Compared with the normotensive subjects, subjects with either persistent or white-coat hypertension had greater mean body mass index, waist-hip ratio, and fasting insulin concentration. On the basis of standardized duplex ultrasound examination of the carotid arteries, mean maximal intimal-medial thickness and plaque index in subjects with white-coat hypertension were greater than among normotensive subjects and equal to that of the subjects with persistent hypertension. CONCLUSION: When compared with unmedicated individuals with comparable elevations in clinic BP, individuals with white-coat hypertension appear not to be protected from the atherosclerotic sequelae of hypertension.     

Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals

Summary We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male (n = 120) and female subjects (n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40–70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, proinsulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A_{1 c}, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia. [Diabetologia (1998) 41: 706–712] Received: 21 August 1997 and in final revised form: 3 February 1998     

Chlamydia pneumoniae seropositivity and early carotid atherosclerosis in a suburban Japanese population

To evaluate the association between Chlamydia pneumoniae (C. pneumoniae) infection and carotid atherosclerosis (CA), we investigated CA assessed by carotid B-mode ultrasound and known or suspected atherosclerotic risk factors including C. pneumoniae IgG and IgA antibodies in 2410 residents (mean age 54.5+/-13.6 years, 697 men) of a suburban Japanese town. CA was found in 30.1% of men and in 14.0% of women, IgG in 59.4% and in 51.4%, and IgA in 36.9% and in 32.4%, respectively. In univariate analysis, most conventional atherosclerotic risk factors and IgA antibody were significantly associated with CA in both sexes, but not IgG. In multivariate logistic regression analysis, independent risk factors for CA were confirmed with age and triglycerides (TG) in men and age, systolic blood pressure, pack-years of smoking, and low-density lipoprotein cholesterol (LDL-C) in women, but not IgG and IgA in either sex. These results do not support C. pneumoniae infection as an important risk factor for CA in this Japanese population.     

Apolipoproteins and carotid artery atherosclerosis in an elderly multiethnic population: the Northern Manhattan stroke study

There is accumulating evidence for a role of tumor necrosis factor-alpha (TNF-alpha) in insulin resistance induced by obesity. The purpose of this study was to investigate whether the TNF alpha/G-308A polymorphism was associated with responses to oral glucose and fat tolerance tests in a case--control study comparing male offspring with a paternal history of premature myocardial infarction (cases, n=335) to age-matched controls (n=340) recruited from 14 European university populations. Genotype frequencies did not significantly differ between cases and controls. Among cases, those carrying the A allele exhibited a higher area under the curve for insulin (64.5 vs 55.9 mU h/l, P=0.009), a higher increment between baseline concentration and peak of insulin (63.1 vs 52.8 mU/l, P=0.005) and a greater decrease between peak and insulin at 120 min (49.1 vs 36.8 mU/l, P=0.003) than those with the GG genotype. No such effect was observed in control subjects. No association was observed with response to a fat tolerance test either in cases or in controls. The present results suggest that the TNF alpha/G-308A polymorphism might interact with other susceptibility factors to coronary heart disease to predispose to insulin resistance, and that the ability of TNF-alpha to induce insulin resistance may extend beyond obesity.     

脑卒中高危人群氧化应激指标与颈动脉粥样硬化危险因素分析

目的调查贵州省福泉县脑卒中高危人群氧化应激指标与颈动脉粥样硬化(CAS)关系,分析CAS相关危险因素。方法采用随机整群抽样法对福泉县6个镇、4个乡常住居民9500例进行健康问卷调查、体格检查、实验室检查、心电图检查及颈动脉彩色超声检查。共筛选出脑卒中高危人群1032例,随机选取高危人群360例,再根据颈部血管彩色超声筛查结果分为颈动脉正常组78例、颈动脉内膜中层厚度(IMT)增厚组131例及CAS组151例,检测氧化应激指标氧化型低密度脂蛋白(ox-LDL)及超氧化物歧化酶(SOD)变化,采用单因素和多因素logistic回归分析CAS的危险因素。结果 CAS组ox-LDL明显高于颈动脉正常组和IMT增厚组[(564.7±70.6)μg/L vs(434.5±46.3)μg/L,(488.1±51.2)μg/L,P<0.05],SOD明显低于颈动脉正常组和IMT增厚组[(41.0±18.1)kU/L vs(67.4±9.5)kU/L,(58.6±10.3)kU/L,P<0.05]。logistic回归分析显示,年龄、吸烟、高血压、脑卒中史或家族史、空腹血糖、LDL-C、ox-LDL升高是导致CAS的独立危险因素。结论加强脑卒中高危人群管理,积极指导控制各项危险因素,调控患者氧化应激反应,可延缓CAS,降低脑卒中发生。     

Weight loss and progression of early atherosclerosis in the carotid artery: a four-year controlled study of obese subjects.

OBJECTIVE: To investigate the extent of carotid artery atherosclerosis in obese subjects and to examine the possible effects of weight loss on atherosclerotic development. DESIGN: Controlled 4 y intervention study. SUBJECTS: 20 obese patients treated with weight-reducing gastroplasty, 19 obese patients treated with dietary recommendations and 35 lean subjects. MEASUREMENTS: Body weight, blood pressure, blood lipids, glucose and insulin were measured. A B-mode ultrasound was recorded to determine the intima-media thickness (IMT) and lumen diameter (LD) of the carotid artery. Study groups were investigated at baseline and re-examined after 3 to 4 y of follow-up. RESULTS: At baseline, obese patients had higher blood pressure, serum total cholesterol, triglycerides, glucose and insulin compared with lean subjects; they also had a larger IMT in the carotid artery bulb (P<0.05) and a larger LD in the common carotid artery (P<0.01). After 4 y of follow-up, obese patients treated with surgery displayed a mean weight loss of 22 kg (19%), while the average weight in the obese control group remained unchanged (P<0.001). The weight loss group showed improvements in blood pressure, HDL-cholesterol, triglycerides and insulin compared with the obese control group (P<0.05). The progression rate of carotid bulb IMT in the weight loss group was similar to that observed in the lean control group (0.024 vs 0.025 mm/y, n.s.), whereas the IMT progression rate was almost three times higher in the obese control group (0.068 mm/y, P<0.05 compared with lean controls). CONCLUSION: Obese people have an unfavourable risk factor profile and signs of premature carotid artery atherosclerosis. Weight loss is followed by an improvement in several risk factors and may reduce the progression rate of atherosclerotic changes in the carotid artery bulb.     

Salivary inflammatory cytokines may be novel markers of carotid atherosclerosis in a Japanese general population: The Suita study

Objective

Salivary biomarkers have been recently useful of periodontal disease, which is also risk factor of atherosclerosis. However, there are few studies of the association between salivary inflammatory cytokines and carotid atherosclerosis. We aimed to clarify the association between salivary inflammatory cytokines and periodontal disease and carotid atherosclerosis in a general urban population.

Methods

We studied 608 Japanese men and women (mean age: 65.4 years) in the Suita study. Carotid atherosclerosis was evaluated by high-resolution ultrasonography with atherosclerotic indexes of intima-media thickness (IMT). Periodontal status was evaluated by the Community Periodontal Index (CPI). Salivary levels of interleukin-1β, interleukin-6, tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured by enzyme linked immunosorbent assay. The risks of carotid atherosclerosis (≥75th percentiles of mean- [0.88 mm] and Max-IMT [1.50 mm]) according to the quartiles of salivary inflammatory cytokines were compared using of adjusted-logistic regression models.

Results and conclusion

All salivary inflammatory cytokines were positively associated with CPI. The adjusted odds ratios for carotid atherosclerosis of mean-IMT in the highest quartile of interleukin-6 and TNF-α were higher than those in the lowest quartiles (OR = 2.32 and 2.88; 95% confidence intervals = 1.19–4.51 and 1.51–5.49, respectively). The adjusted odds ratio for carotid atherosclerosis of mean-IMT in the highest quartile of PGE2 was greater than those in the lowest quartile in women (OR = 2.78; 95% confidence intervals = 1.11–6.95). In conclusion, higher levels of salivary inflammatory cytokines were associated with both periodontal disease and carotid atherosclerosis. Selected salivary inflammatory cytokines may be useful screening markers for periodontal disease and carotid atherosclerosis.     

Progression of carotid atherosclerosis in Japanese patients with coronary artery disease

The authors investigated the relationship between the progression of carotid atherosclerosis and the severity of coronary artery disease (CAD). The two-year follow-ups of extracranial carotid atherosclerosis in 50 patients with CAD were evaluated by B-mode high-resolution ultrasonography. The summed maximal thickness of carotid plaques increased by 3.2 to 10.1 mm (mean 1.06 mm, SD 2.42 mm). The extent of coronary atherosclerosis (p<0.02) and the serum total cholesterol level (p<0.01) were different between the progressing group (n=20) and the nonprogressing group (n=25) with carotid atherosclerosis. Carotid disease progression was significantly higher in patients with three-vessel coronary disease than in those without significant coronary disease (p<0.005). Age, serum triglyceride, high-density lipoprotein-cholesterol, pack-years of smoking, % smokers, % hypertensives, and % diabetics were not different between the two groups. It was concluded that the severity of CAD was one of the strong predictors for carotid disease progression in patients with CAD.     

Sex‐specific risk factors of carotid atherosclerosis progression in a high‐risk population of cardiovascular disease

BackgroundThe progression of carotid intima‐media thickness (cIMT) and plaques are associated with cardiovascular health, especially for high‐risk population of cardiovascular disease (CVD).HypothesisRisk factors for atherosclerosis may vary by sex. This study aimed to investigate the sex‐specific risk factors of cIMT and plaque progression.MethodsWe selected subjects who were identified as high‐risk population of CVD, and collected their carotid ultrasound data and baseline characteristics. Linear regression and logistic regression analyses were used to identify risk factors for cIMT and plaque progression. Sex‐specific risk factors were identified respectively.ResultsA total of 7908 participants were included. The mean age was 57.75 ± 9.45 years and 61.51% were female. During mean follow‐up of 1.92 ± 0.89 years, the median annual cIMT change rate was −7.25 μm/year. Seven hundred and fifteen subjects free from plaques at baseline developed plaque. Age, smoking, hypertension, and diabetes were common risk factors for carotid atherosclerosis progression in all participants. Smoking and alcohol drinking were significantly associated with increased cIMT change in women, while hypertension and antihypertensive medication were significant in men. Increased total cholesterol and diabetes were significantly associated with new plaque presence in women, while smoking, increased triglyceride, and dyslipidemia were significant in men (p ˂ .05 for all cases). The association of baseline cIMT and smoking with annual cIMT change rate and increased total cholesterol with new plaque presence were significantly differentiated between both sexes (p for interaction ˂ .05).ConclusionsThe risk factors for cIMT and plaque progression differed by sex.     

Strong and significant relationships between aggregation of major coronary risk factors and the acceleration of carotid atherosclerosis in the general population of a Japanese city: the Suita Study

BACKGROUND: Carotid arterial intimal-medial thickness (IMT) measured by high-resolution B-mode ultrasonography has come to be used as a noninvasive surrogate end point to measure progression of atherosclerosis. However, there are no detailed data on the relationship between aggregation of coronary risk factors and carotid atherogenesis. METHODS: Cross-sectional assessment of the relationship between carotid atherosclerosis detected by high-resolution ultrasonography and integration of major coronary risk factors by age and sex. Subjects aged 30 to 86 years were randomly selected from Suita, located in Osaka, the second largest urban area of Japan, including 1896 men and 2102 women. Carotid atherosclerosis was evaluated by using our atherosclerotic indexes of IMT, plaque number, plaque score, and percentage of stenosis of the carotid artery assessed using ultrasonography by sex and age group classified by number of major coronary risk factors (ie, hypertension [diastolic blood pressure > or =90 mm Hg and/or systolic blood pressure > or 140 mm Hg or receiving medication], smoking [current smoker], and hypercholesterolemia [serum total cholesterol level > or =5.68 mmol/L [220 mg/dL] or receiving medication]). RESULTS: The mean carotid atherosclerotic index value, especially the mean IMT value, of the subjects with 1 major coronary risk factor was on average 0.028 mm (3.2%) higher for men and 0.025 mm (2.9%) higher for women than that of the subjects without major coronary risk factors; for subjects with 2 risk factors, 0.054 mm (6.3%) higher for men and 0.053 mm (6.2%) higher for women; and for high-risk subjects with 3 major risk factors, 0.135 mm (15.8%) higher for men and 0.137 mm (15.4%) higher for women. The percentage of the subjects with severe stenosis of at least 50% increased stepwise with increases in the number of coronary risk factors and showed a significant difference (P<.05) between men and women, ie, 2.4% vs 0. 6% (P =.01) among the subjects with no risk factors; 6.7% vs 1.5% (P<.001), subjects with 1 risk factor; 10.7% vs 2.7% (P<.001), subjects with 2 risk factors; and 18.6% vs 5.0% (P =.01), high-risk subjects. CONCLUSIONS: Aggregation of established major coronary risk factors strongly influenced carotid atherogenesis in both sexes. There were significant differences between sexes in the acceleration or progression of carotid atherosclerosis.     

Association of microalbuminuria and atherosclerotic risk factors in non-diabetic subjects in Korea

Microalbuminuria in non-diabetic subjects is reportedly associated with increased cardiovascular morbidity and mortality. The prevalence of microalbuminuria in non-diabetic subjects varies widely from 5–6% in the UK and USA to 30–55% in Finland, Mexico, or Australian Aborigines. We studied cross-sectionally 497 clinically healthy, non-diabetic subjects more than 40 years of age who were living in Seoul, Korea for the prevalence of microalbuminuria and various cardiovascular risk factors. Urinary albumin–to–creatinine ratio (UACR) was determined in morning spot urine samples. Subjects were divided into normoalbuminuria (UACR <2 mg/mmol) and microalbuminuria (UACR ≥2 mg/mmol) groups. A total of 61 (12.2%) out of 497 subjects were found to have microalbuminuria. Subjects with microalbuminuria had significantly higher values in age, body mass index (BMI), waist-to-hip ratio in women, systolic and diastolic blood pressure, prevalence of hypertension, plasma cholesterol and triglyceride, and fasting plasma insulin. When subjects with microalbuminuria were compared with age-, sex-, and BMI-matched controls without microalbuminuria, systolic and diastolic blood pressure, and fasting plasma insulin concentrations were higher in microalbuminuric subjects. Multiple logistic regression analysis showed that fasting plasma insulin level and systolic blood pressure were independently associated with microalbuminuria. These results indicate that the prevalence of microalbuminuria in Korean non-diabetic subjects is lower than that in Mexico and Finland, but similar to that in Caucasians from the UK and USA, or in Pima Indians. Also, microalbuminuria in Korean non-diabetic subjects is associated with atherosclerotic risk factors such as hyperinsulinemia and hypertension, suggesting that microalbuminuria in these subjects may be a feature of insulin resistance syndrome.