Microalbuminuria accounts for the increased vascular disease risk in diabetic patients with metabolic syndrome

The aim of this study was to determine the impact of the metabolic syndrome on vascular disease risk in patients with type-2 diabetes. A prospective cohort study was carried out. The main dependent variable was the combination of coronary disease, stroke and lower leg amputation. Cox regression modeling was used. In total, 317 patients were followed for a mean of 7.7 years. The prevalence of metabolic syndrome was 87%. Multivariate analysis identified the following as predictors of incident vascular disease: age (relative risk [RR] =1.06, 95% confidence interval [CI], 1.02-1.1; P=.0003), baseline cardiovascular disease (RR=1.8; 95% CI, 1.1-3.0; P=.017), and the simultaneous presence of four metabolic risk factors (RR=5.8; 95% CI, 1.8-18; P=.003). The most predictive factor was microalbuminuria (chi2=5.9; P=.015). Microalbuminuria accounts for the increased risk of vascular disease in patients with metabolic syndrome. In evaluating vascular disease risk in patients with type-2 diabetes, it is more important to consider the total number of metabolic risk factors than the presence of metabolic syndrome alone.     

A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women

We examined the relationship of maturity-onset clinical diabetes mellitus with the subsequent incidence of coronary heart disease, stroke, total cardiovascular mortality, and all-cause mortality in a cohort of 116,177 US women who were 30 to 55 years of age and free of known coronary heart disease, stroke, and cancer in 1976. During 8 years of follow-up (889 255 person-years), we identified 338 nonfatal myocardial infarctions, 111 coronary deaths, 259 strokes, 238 cardiovascular deaths, and 1349 deaths from all causes. Diabetes was associated with a markedly increased risk of nonfatal myocardial infarction and fatal coronary heart disease (age-adjusted relative risk [RR] = 6.7; 95% confidence interval [CI], 5.3 to 8.4), ischemic stroke (RR = 5.4; 95% CI, 3.3 to 9.0), total cardiovascular mortality (RR = 6.3; 95% CI, 4.6 to 8.6), and all-cause mortality (RR = 3.0; 95% CI, 2.5 to 3.7). A major independent effect of diabetes persisted in multivariate analyses after simultaneous control for other known coronary risk factors (for these end points, RR [95% CI] = 3.1 [2.3 to 4.2], 3.0 [1.6 to 5.7], 3.0 [1.9 to 4.8], and 1.9 [1.4 to 2.4], respectively). The absolute excess coronary risk due to diabetes was greater in the presence of other risk factors, including cigarette smoking, hypertension, and obesity. These prospective data indicate that maturity-onset clinical diabetes is a strong determinant of coronary heart disease, ischemic stroke, and cardiovascular mortality among middle-aged women. The adverse effect of diabetes is amplified in the presence of other cardiovascular risk factors, many of which are modifiable.     

Menstrual cycle irregularity and risk for future cardiovascular disease

Cross-sectional studies suggest that women who have irregular menstrual cycles and hyperandrogenism may be at increased risk for cardiovascular disease (CVD). However, prospective data are lacking on the relationship between menstrual cycle irregularity and subsequent CVD risk. The objective of this study was to assess prospectively the risk for coronary heart disease (CHD) and stroke associated with a history of irregular menstrual cycles. The study design was a prospective cohort study of 82,439 female nurses who provided information in 1982 on prior menstrual regularity (at ages 20-35 yr) and were followed through 1996 for cardiovascular events. Incident reports of nonfatal myocardial infarction, fatal CHD, and nonfatal and fatal stroke were made. Medical records were reviewed for confirmation. During 14 yr (1,155,915 person-yr) of follow-up, there were 1417 incident cases of CHD and 838 incident cases of stroke, including 471 cases of ischemic stroke. Compared with women reporting a history of very regular menstrual cycles, women reporting usually irregular or very irregular cycles had an increased risk for nonfatal or fatal CHD [age-adjusted relative risks (RR), 1.25 and 1.67, respectively; 95% confidence intervals (CI), 1.07-1.47 and 1.35-2.06, respectively]. Increased risks for CHD associated with prior cycle irregularity remained significant after adjustment for body mass index and several potential confounders. There was a nonsignificant increase in overall stroke risk (RR, 1.30; 95% CI = 0.97-1.74) and in ischemic stroke risk (RR, 1.40; 95% CI = 0.97-2.04) associated with very irregular cycles. Menstrual cycle irregularity may be a marker of metabolic abnormalities predisposing to increased risk for CVD.     

Effect of metabolic syndrome or type II diabetes mellitus on the occurrence of recurrent vascular events in hypertensive patients

Patients with hypertension and manifest vascular disease are at high risk for recurrent cardiovascular diseases. It is unknown if the metabolic syndrome further increases the risk in these patients. This study aims to quantify the effect of metabolic syndrome and type II diabetes on cardiovascular events in hypertensive patients with vascular disease. A total of 2,196 hypertensive patients with vascular disease (cerebrovascular disease (34%), coronary heart disease (50%), peripheral arterial disease (28%), abdominal aortic aneurysm (13%)) from the Second Manifestations of Arterial Disease study were followed for up to 10 years (mean 3.9 years) for death, stroke and myocardial infarction. Age and sex adjusted hazard ratios (HR) were calculated for hypertensive patients with metabolic syndrome but without diabetes (n=775) and for hypertensive patients with type II diabetes (n=381), compared to merely hypertensive patients (n=1,040). Forty-nine percent had metabolic syndrome (NCEP ATPIII definition) and 17% had type II diabetes. Metabolic syndrome predicted vascular death (HR 1.41, 95% confidence interval (CI) 1.01-1.98), stroke (HR 1.36, 95% CI 0.85-2.16) and myocardial infarction (HR 1.40, 95% CI 0.97-2.01). Type II diabetes accounted for even higher risks of vascular end points (HR 1.41-1.64). The effect of metabolic syndrome on future events could not be explained by the presence of type II diabetes. Even in high-risk patients with hypertension and vascular disease, presence of metabolic syndrome or type II diabetes identifies patients at high risk for future cardiovascular events. Identifying metabolic syndrome patients may direct therapy focusing on treatment of insulin resistance by reducing weight and increasing physical activity.     

Effecacy of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors for prevention of stroke

OBJECTIVE: To determine if 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in preventing fatal and nonfatal strokes in patients at increased risk of coronary artery disease. DESIGN: Meta-analysis of randomized controlled trials. Clinical trials were identified by a computerized search of MEDLINE (1983 to June 1996), by an assessment of the bibliographies of published studies, meta-analyses and reviews, and by contacting pharmaceutical companies that manufacture statins. Trials were included in the analysis if their patients were randomly allocated to a statin or placebo group, and reported data on stroke events. Thirteen of 28 clinical trials were selected for review. Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, cholesterol measurements, and the number of fatal and nonfatal stroke events in each arm of therapy. Missing data on stroke events were obtained by contacting the investigators of the clinical trials. MAIN RESULTS: Among 19,921 randomized patients, the rate of total stroke in the placebo group was 2.38% (90% nonfatal and 10% fatal). In contrast, patients who received statins had a 1.67% stroke rate. Using an exact stratified analysis, the pooled odds ratio (OR) for total stroke was 0.70 (95% confidence interval [CI] 0.57, 0.86; p =.0005). The pooled OR for nonfatal stroke was 0.64 (95% CI 0.51, 0.79; p =.00001), and the pooled OR for fatal stroke was 1.25 (95% CI 0.71, 2.24; p =.4973). In separate analyses, reductions in total and nonfatal stroke risk were found to be significant only for trials of secondary coronary disease prevention. Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the relative risk for any stroke outcome. CONCLUSIONS: The available evidence clearly shows that HMG-CoA reductase inhibitors reduce the morbidity associated with strokes in patients at increased risk of cardiac events. Data from 13 placebo-controlled trials suggest that on average one stroke is prevented for every 143 patients treated with statins over a 4-year period.     

The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study.

OBJECTIVES: This analysis from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study assesses the effects of pioglitazone on mortality and macrovascular morbidity in patients with type 2 diabetes and a previous myocardial infarction (MI). BACKGROUND: People with type 2 diabetes have an increased incidence of MI compared with the general population. Those with diabetes and MI have a worse prognosis than nondiabetic patients with cardiovascular disease. METHODS: The PROactive study was a prospective, multicenter, double-blind, placebo-controlled trial of 5,238 patients with type 2 diabetes and macrovascular disease. Patients were randomized to either pioglitazone or placebo in addition to their other glucose-lowering and cardiovascular medication. Treatment of diabetes, dyslipidemia, and hypertension was encouraged according to the International Diabetes Federation guidelines. Patients were followed for a mean of 2.85 years. The primary end point was the time to first occurrence of macrovascular events or death. Of the total cohort, the subgroup of patients who had a previous MI (n = 2,445 [46.7%]; n = 1,230 in the pioglitazone group and n = 1,215 in the placebo group) was evaluated using prespecified and post-hoc analyses. RESULTS: Pioglitazone had a statistically significant beneficial effect on the prespecified end point of fatal and nonfatal MI (28% risk reduction [RR]; p = 0.045) and acute coronary syndrome (ACS) (37% RR; p = 0.035). There was a 19% RR in the cardiac composite end point of nonfatal MI (excluding silent MI), coronary revascularization, ACS, and cardiac death (p = 0.033). The difference in the primary end point defined in the main PROactive study did not reach significance in the MI population (12% RR; p = 0.135). The rates of heart failure requiring hospitalization were 7.5% (92 of 1,230) with pioglitazone and 5.2% (63 of 1,215) with placebo. Fatal heart failure rates were similar (1.4% [17 of the 92] with pioglitazone versus 0.9% [11 of the 63] with placebo). CONCLUSIONS: In high-risk patients with type 2 diabetes and previous MI, pioglitazone significantly reduced the occurrence of fatal and nonfatal MI and ACS. (PROspective pioglitAzone Clinical Trial In macroVascular Events; http://www.clinicaltrials.gov/ct/show/NCT00174993?order = 1; ISRCTN NCT00174993).     

Adverse prognosis associated with the metabolic syndrome in established coronary artery disease: data from the EUROPA trial

Objective

To assess the prevalence of metabolic syndrome, and its effect on cardiovascular morbidity and mortality in patients with established coronary disease and to explore the inter‐relationships between metabolic syndrome, diabetes, obesity and cardiovascular risk.

Methods

The presence of metabolic syndrome was determined in 8397 patients with stable coronary disease from the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease, with mean follow‐up of 4.2 years. Metabolic syndrome was defined using a modified version of the National Cholesterol Education Programme criteria.

Results

Metabolic syndrome was present in 1964/8397 (23.4%) of the population and significantly predicted outcome; relative risk (RR) of cardiovascular mortality  =  1.82 (95% CI 1.40 to 2.39); and fatal and non‐fatal myocardial infarction RR = 1.50 (95% CI 1.24 to 1.80). The association with adverse outcomes remained significant after adjustment, RR of cardiovascular mortality after adjustment for conventional risks and diabetes  =  1.39 (95% CI 1.03 to 1.86). In comparison with normal weight subjects without diabetes or metabolic syndrome, normal weight dysmetabolic subjects (with either diabetes or metabolic syndrome) were at substantially increased risk of cardiovascular death (RR = 4.05 (95% CI 2.38 to 6.89)). The relative risks of cardiovascular death for overweight and obese patients with dysmetabolic status were nominally lower (RR = 3.01 (95% CI 1.94 to 4.69) and RR = 2.35 (95% CI 1.50 to 3.68), respectively).

Conclusions

Metabolic syndrome is associated with adverse cardiovascular outcome, independently of its associations with diabetes and obesity. A metabolic profile should form part of the risk assessment in all patients with coronary disease, not just those who are obese.     

Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to lower blood pressure, but little is known about its long-term effect on cardiovascular end points. Our objective was to assess the association between a DASH-style diet adherence score and risk of coronary heart disease (CHD) and stroke in women. METHODS: In this prospective cohort study, diet was assessed 7 times during 24 years of follow-up (1980-2004) with validated food frequency questionnaires. A DASH score based on 8 food and nutrient components (fruits, vegetables, whole grains, nuts and legumes, low-fat dairy, red and processed meats, sweetened beverages, and sodium) was calculated. Lifestyle and medical information was collected biennially with a questionnaire. The Cox proportional hazard model was used to adjust for potential confounders. The study population comprised 88,517 female nurses aged 34 to 59 years without a history of cardiovascular disease or diabetes in 1980. The main outcome measures were the numbers of confirmed incident cases of nonfatal myocardial infarction, CHD death, and stroke. RESULTS: We documented 2129 cases of incident nonfatal myocardial infarction, 976 CHD deaths, and 2317 [corrected] cases of stroke. After adjustment for age, smoking, and other cardiovascular risk factors, the relative risks of CHD across quintiles of the DASH score were 1.0, 0.99, 0.86, 0.87, and 0.76 (95% confidence interval, 0.67-0.85) (P<.001 for trend). The magnitude of risk difference was similar for nonfatal myocardial infarction and fatal CHD. The DASH score was also significantly associated with lower risk of stroke (multivariate relative risks across quintiles of the DASH score were 1.0, 0.92, 0.91, 0.89, and 0.82) (P=.002 for trend). Cross-sectional analysis in a subgroup of women with blood samples showed that the DASH score was significantly associated with lower plasma levels of C-reactive protein (P=.008 for trend) and interleukin 6 (P=.04 for trend). CONCLUSION: Adherence to the DASH-style diet is associated with a lower risk of CHD and stroke among middle-aged women during 24 years of follow-up.     

Effect of Tight Blood Glucose Control Versus Conventional Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review with Meta‐Analysis of Randomized Controlled Trials

Tight control of blood glucose reduces cardiovascular events and total mortality is conflicting. To summarize clinical effects of tight versus conventional glucose control in patients with type 2 diabetes. We systematically searched MEDLINE, EMBASE, Cochrane Library, and ISI Web of Knowledge with no limits of language and time. Further trials were searched from the reference lists of identified studies. We included randomized controlled comparing different levels of blood glucose control intensity in type 2 diabetic patients. Two independent reviewers extracted data of eligible studies using standard case report forms. We investigated total mortality, cardiovascular and microvascular events, and hypoglycemia in patients with type 2 diabetes. We used random‐effects models to obtain relative risks (RR) with 95% confidence intervals (CI). We included 6 trials involving 27,654 patients. There was no significant effect of tight blood glucose control on all‐cause mortality (RR 1.03; 95% CI 0.90–1.17) or cardiovascular mortality (RR 1.04; 95% CI 0.83–1.29). Tight glucose control reduced the risk for nonfatal MI (RR 0.85; 95% CI 0.76–0.95), although had no effect on the incidence of nonfatal stroke (RR 1.02; 95% CI 0.88–1.17). For microvascular events, tight glucose control reduced the risk progression of retinopathy (RR 0.80; 95% CI 0.71–0.91), incidence of peripheral neuropathy (RR 0.94; 95% CI 0.89–0.99), and progression of nephropathy (RR 0.55; 95% CI 0.37–0.80), but had not significant effect on the incidence of nephropathy (RR 0.69; 95% CI 0.42–1.14). The risk of severe hypoglycemia increased with tight glucose control (RR 2.39; 95% CI 1.79–3.18). Tight blood glucose control reduces the risk for some macrovascular and microvascular events, without effect on all‐cause mortality and cardiovascular mortality. Tight glucose control increases the risk of severe hypoglycemia.     

Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, active, controlled clinical trial conducted to determine whether newer antihypertensive agents, including doxazosin, an alpha-blocker, differ from chlorthalidone, a diuretic, with respect to coronary heart disease (CHD) and other cardiovascular disease (CVD) events in hypertensive patients at high risk of CHD. In February 2000, the doxazosin treatment arm was discontinued, and findings through December 1999 were reported. This report includes an additional 9232 participant-years and 939 CVD events. At 623 clinical centers, patients (aged >or=55 years) with hypertension and at least 1 other CHD risk factor were randomly assigned to either chlorthalidone or doxazosin. The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; prespecified secondary outcome measures included all-cause mortality, stroke, combined CHD (fatal CHD, nonfatal MI, hospitalized angina, and coronary revascularization), and combined CVD (combined CHD, stroke, angina treated outside the hospital, heart failure, and peripheral arterial disease). Mean follow-up was 3.2 years. There was no difference in primary outcome between the arms (relative risk [RR], 1.02; 95% confidence interval [CI], 0.92 to 1.15). All-cause mortality also did not differ (RR, 1.03; 95% CI, 0.94 to 1.13). However, the doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke (RR, 1.26; 95% CI, 1.10 to 1.46) and combined CVD (RR 1.20; 95% CI, 1.13 to 1.27). These findings confirm the superiority of diuretic-based over alpha-blocker-based antihypertensive treatment for the prevention of CVD.     

Ischemic stroke: A cardiovascular risk equivalent? Lessons learned from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

Statin therapy in patients with coronary artery disease or in those at risk for cardiovascular disease is associated with a reduced incidence of ischemic stroke. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial showed treatment with atorvastatin 80 mg daily in patients with a recent stroke or transient ischemic attack (TIA) reduces the incidence of fatal and nonfatal stroke by 16%. In this population with a recent stroke or TIA, coronary artery disease events and the need for revascularization were a frequent occurrence. Furthermore, the relative reduction of noncerebrovascular events and the need for revascularization was greater with atorvastatin than the reduction of stroke. A patient with a recent ischemic stroke or TIA is at high risk for fatal and nonfatal coronary events (approximately 4% per year), and according to most guidelines for the management of coronary artery disease, such patients should be in the high risk category. Consequently, ischemic stroke should be considered to be a coronary risk equivalent with a prognosis similar to that of a patient with coronary artery disease. Furthermore, both the stroke and coronary artery disease prognoses are improved by treatment with atorvastatin 80 mg daily.     

小剂量阿司匹林对心血管病一级预防效果及安全性的系统评价

目的 系统评价小剂量阿司匹林在高危人群中一级预防心血管病的有效性和安全性.方法 计算机检索MEDLINE、EMbase、Cochrane图书馆(2008年第3期)、中国生物医学文献数据库、中国学术期刊全文数据库,同时筛检了纳入文献的参考文献.收集小剂量阿司匹林(75～150 mg)一级预防心血管病的随机对照试验(RCT),2名评价员独立评价文献质量和提取资料,并采用RevMan4.2软件对资料进行荟萃分析.结果 共纳入6个研究(TPT,HOT,PPP,WHS,POPADAD,JPAD),72 466例患者.(1)小剂量阿司匹林总的心血管事件的发生率(RR=0.85,95% CI:0.80～0.92)、卒中发生率(RR=0.87,95% CI:0.77～0.98)、非致死性卒中发生率(RR=0.81,95%CI:0.70～0.95)、短暂脑缺血发作发生率(RR=0.76,95%CI:0.64～0.90)均低于安慰剂(均P＜0.05).(2)小剂量阿司匹林非致死性心肌梗死(RR=0.89,95%CI:0.77～1.02)、心血管性死亡(RR=0.98,95% CI:0.86～1.13)、全因死亡发生率(RR=0.95,95%CI:0.88～1.02)与安慰剂比较,差异无统计学意义(P＞0.05).(3)在老年人群中分析显示,小剂量阿司匹林冠心病的发生率低于安慰剂(RR=0.81,95%CI:0.70～0.94,P＜0.01).(4)在安全性方面,与安慰剂比较,小剂量阿司匹林有出血并发症的风险(RR=1.15,95%CI:1.12～1.18,P＜0.01),而在过敏反应方面差异无统计学意义(P＞0.05).结论 小剂最阿司匹林能降低总的心血管事件、短暂脑缺血发作、卒中、非致死性卒中的发生率;对降低非致死性心肌梗死、心血管性死亡、全因死亡方面效果不明显;在老年人群中小剂量阿司匹林能降低冠心病的发牛率;长期应用无明显过敏反应,但存在出血并发症的风险.     

Association of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke

CONTEXT: Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults. OBJECTIVE: The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke. DESIGN AND PARTICIPANTS: A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study. MAIN OUTCOME MEASURES: A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study. RESULTS: Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P<0.05) but not with risk of fatal MI or fatal coronary heart disease. CONCLUSION: Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.     

Cardiovascular risk profile and morbidity in subjects affected by type 2 diabetes mellitus with and without diabetic foot

Diabetic foot syndrome (DFS) is the most frequent cause of hospitalization of diabetic patients and one of the most economically demanding complications of diabetes. People with diabetes have been shown to have higher mortality than people without diabetes. On this basis, the aim of our study was to evaluate the possible role of diabetic foot as a cardiovascular risk marker in patients with type 2 diabetes mellitus. We enrolled 102 consecutive patients with type 2 diabetes mellitus with diabetic foot and 123 patients with type 2 diabetes mellitus without limb lesions to compare the prevalence of main cardiovascular risk factors, subclinical cardiovascular disease, previous cardiovascular morbidity, and incidence of new vascular events on a 5-year follow-up. Diabetic patients with diabetic foot were more likely to have a higher prevalence of cardiovascular risk factors such as hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and microalbuminuria or proteinuria, a higher prevalence of a previous cardiovascular morbidity (coronary artery disease, transient ischemic attack/ischemic stroke, diabetic retinopathy), and a higher prevalence of subclinical cardiovascular disease. Furthermore, diabetic patients with foot ulceration showed, on a 5-year follow-up, a higher incidence of new-onset vascular events (coronary artery disease, transient ischemic attack/ischemic stroke, diabetic retinopathy). At multivariate analysis, duration of diabetes, age, hemoglobin A1c, and DFS maintained a significant association with cardiovascular morbidity; but DFS presence showed the highest hazard ratio.     

Prognostic value of treadmill exercise echocardiography

INTRODUCTION AND OBJECTIVES: Exercise echocardiography (EE) is useful for diagnosing coronary disease, but little is known about its value for risk stratification. We aimed to determine: a) whether data from EE supplemented clinical data and data from exercise testing and resting echocardiography in predicting cardiac events; and b)whether the number and location of abnormal regions and their responses to exercise influenced risk stratification. PATIENTS AND METHOD: The 2,436 patients referred for EE were followed up for 2.1+/-1.5 years. Some 120 serious cardiovascular events (i.e., non-fatal myocardial infarction or cardiovascular death) occurred before revascularization. RESULTS: In 1203 patients (49%), EE gave abnormal results. There were 89 events in patients with an abnormal result (7.3%) and 31 in those with a normal result (2.5%; P<.0001). Multivariate analysis of clinical data, and data from exercise testing, resting echocardiography, and EE showed that male sex (RR=1.7; 95% CI, 1.1-2.8; P=.02), metabolic equivalents or METs (RR=0.9; 95% CI, 0.86-0.98; P=.01), peak heart rate x blood pressure (RR= 0.9;95% CI, 0.9; P=.002), resting wall motion score index (RR=2.5; 95% CI, 1.5-4.1; P<.0001), and number of abnormal regions at peak exercise (RR=1.4; 95% CI, 1.2-1.7; P<.0001) were independently associated with the risk of a serious event (final model chi2, 170; incremental P<.0001). The same variables, excluding sex, were independently associated with cardiovascular death (final model chi2, 169; incremental P=.01). CONCLUSIONS: Exercise echocardiography supplements clinical data and data from exercise testing and resting echocardiography in patients with known or suspected coronary artery disease.     

Impact of metabolic syndrome and diabetes mellitus on cardiovascular events in coronary artery disease without ischemia on stress thallium-201 single photon emission computed tomography after percutaneous coronary intervention

OBJECTIVES: The metabolic syndrome defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) is a predictor of cardiovascular events. However, the significance of metabolic syndrome for cardiovascular events has been not clarified in Japan. The impact of metabolic syndrome and diabetes mellitus on cardiovascular events was investigated, especially in the high risk group after percutaneous coronary intervention. METHODS: We studied 456 patients (mean age 63 +/- 10 years, range 36-88 years) without ischemia on stress thallium-201 single photon emission computed tomography after percutaneous coronary intervention. The diagnosis of metabolic syndrome was made according to the modified NCEP ATP III criteria. Cardiovascular events were examined for mean 3.7 +/- 1.8 years (range 2.0-8.7 years). There were 196 patients without diabetes mellitus or metabolic syndrome (Group D - M -), 89 patients without diabetes mellitus but with metabolic syndrome (Group D - M +), 61 patients with diabetes mellitus but without metabolic syndrome (Group D + M -), and 110 patients with both diabetes mellitus and metabolic syndrome (Group D + M +). RESULTS: The event-free survival curve in Group D - M + was significantly lower than that in Group D - M - (p < 0.05), but not different from that in Group D + M -. The survival curve was markedly lower in Group D + M + than that in Group D - M + (p < 0.005). The Cox proportional hazard model revealed that diabetes mellitus and metabolic syndrome were independent significant risk factors for events. CONCLUSIONS: The diagnosis of metabolic syndrome was helpful for identification of patients with high cardiovascular event rate even in patients after percutaneous coronary intervention. The combination of metabolic syndrome and diabetes mellitus markedly increases the risk for cardiovascular events.     

Association between hypertensive urgencies and subsequent cardiovascular events in patients with hypertension

OBJECTIVE: To determine whether patients with hypertensive urgency have a higher risk for subsequent cardiovascular events compared with hypertensive patients without this event. METHODS: Overall, 384 patients with hypertensive urgency and 295 control patients were followed up for at least 2 years. Hypertensive urgency was defined as a systolic blood pressure above 220 mmHg and/or a diastolic blood pressure above 120 mmHg without any evidence of acute end-organ damage. The control group consisted of patients admitted to the emergency department with a systolic blood pressure between 135 to 180 mmHg and a diastolic blood pressure between 85-110 mmHg. The number of cardiovascular events defined as acute coronary syndrome, acute stroke, atrial fibrillation, acute left ventricular failure and aortic aneurysm were consecutively analyzed during follow-up. The median follow-up time was 4.2 years (interquartile range 2.9-5.7 years). Twenty-six patients of the urgency group and 23 patients of the control group were lost for follow-up. RESULTS: Overall, 117 (17%) patients had nonfatal clinical cardiovascular events and 13 had (2%) fatal cardiovascular events. The frequency of cardiovascular events was significantly higher in patients with hypertensive urgencies (88 vs. 42; P = 0.005). The Cox regression analysis identified age (P < 0.001) and hypertensive urgencies (P = 0.035) as independent predictors for subsequent cardiovascular events. CONCLUSIONS: Hypertensive urgencies are associated with an increased risk for subsequent cardiovascular events in patients with arterial hypertension.     

Hypercholesterolemia. The evidence supports use of statins

Using statins to treat older men and women with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, Intermittent claudication, and congestive heart failure. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg in older patients with CAD, prior stroke, peripheral arterial disease, extracranial carotid arterial disease, abdominal aortic aneurysm, diabetes meilitus, and the metabolic syndrome. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia without cardiovascular disease. Consider using statins in older persons without cardiovascular disease but with a serum LDL cholesterol > or = 130 mg/dL, or a serum high-density lipoprotein cholesterol < 50 mg/dL. Data from the Heart Protection Study favor treating patients at high risk for vascular events with statins regardless of age or initial serum lipids.     

Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events: The ODYSSEY OUTCOMES Trial

Background

The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths.

Prognostic value of ambulatory heart rate revisited in 6928 subjects from 6 populations

The evidence relating mortality and morbidity to heart rate remains inconsistent. We performed 24-hour ambulatory blood pressure monitoring in 6928 subjects (not on beta-blockers; mean age: 56.2 years; 46.5% women) enrolled in prospective population studies in Denmark, Belgium, Japan, Sweden, Uruguay, and China. We computed standardized hazard ratios for heart rate, while stratifying for cohort, and adjusting for blood pressure and other cardiovascular risk factors. Over 9.6 years (median), 850, 325, and 493 deaths accrued for total, cardiovascular, and noncardiovascular mortality, respectively. The incidence of fatal combined with nonfatal end points was 805, 363, 439, and 324 for cardiovascular, stroke, cardiac, and coronary events, respectively. Twenty-four-hour heart rate predicted total (hazard ratio: 1.15) and noncardiovascular (hazard ratio: 1.18) mortality but not cardiovascular mortality (hazard ratio: 1.11) or any of the fatal combined with nonfatal events (hazard ratio: < or =1.02). Daytime heart rate did not predict mortality (hazard ratio: < or =1.11) or any fatal combined with nonfatal event (hazard ratio: < or =0.96). Nighttime heart rate predicted all of the mortality outcomes (hazard ratio: > or =1.15) but none of the fatal combined with nonfatal events (hazard ratio: < or =1.11). The night:day heart rate ratio predicted total (hazard ratio: 1.14) and noncardiovascular mortality (hazard ratio: 1.12) and all of the fatal combined with nonfatal events (hazard ratio: > or =1.15) with the exception of stroke (hazard ratio: 1.06). Sensitivity analyses, in which we stratified by risk factors or from which we excluded 1 cohort at a time or the events occurring within 2 years of enrollment, showed consistent results. In the general population, heart rate predicts total and noncardiovascular mortality. With the exception of the night:day heart rate ratio, heart rate did not add to the risk stratification for fatal combined with nonfatal cardiovascular events. Thus, heart rate adds little to the prediction of cardiovascular risk.