Rate Of Major Coronary Events Research Articles

Abstract 16688: Effects of Evolocumab in Patients With Prior Percutaneous Coronary Intervention: An Analysis From the Fourier Trial

Introduction: Among patients with atherosclerotic cardiovascular disease (ASCVD), those with history of PCI represent an important population for potential high risk for cardiovascular (CV) events. We examined the clinical efficacy of the PCSK9 inibitor evolocumab in patients with prior PCI. Methods: FOURIER randomized 27,564 patients with ASCVD on statin therapy to evolocumab or placebo with a median follow-up of 2.2 yrs. The primary end point (PEP) was the composite of CV death, MI, stroke, unstable angina, or coronary revascularization; major coronary events were the composite of coronary death, MI, or coronary revascularization. The risk of events in patients with and without a history of PCI were compared in the placebo arm. The clinical benefit of evolocumab vs. placebo was compared using a Cox proportional hazards model. Results: 17,073 (62%) patients had prior PCI at baseline. Among patients in the placebo arm, those with prior PCI (N=8563) had a 1.6x higher rate of the PEP (16.8 vs 10.7%; adjusted HR 1.61; 95% CI 1.42-1.84 P<0.0001) and nearly double the rate of major coronary events (14.5 vs. 7.8%; P<0.0001; adjusted HR 1.72; 95% CI 1.49-1.99; Figure left). In patients with prior PCI, evolocumab reduced the risk of the PEP by 16% (HR 0.84; 95% CI 0.77-0.91; P<0.0001) and of major coronary events by 18% (HR 0.82; 95% CI 0.75-0.90, P<0.0001; Figure right), including a 30% reduction in fatal or non-fatal MI (P<0.001) and a 24% reduction in coronary revascularization (P<0.001). After the first year, there was a 25% reduction in major coronary events (HR 0.75, 95% CI 0.66-0.86, P<0.0001). The absolute risk reduction at 3 years with evolocumab for major coronary events was 2.8% in patients with prior PCI vs. 0.3% in those without. Conclusions: In a contemporary cohort with ASCVD on statin therapy, patients with prior PCI were at heightened risk for coronary events. Evolocumab was highly effective in this group, reducing major coronary events by 18% with a NNT at 3 years of only 36.

The Impact of Set-Up Uncertainty on Dose-Response Estimates

The landmark study by Darby reported that “rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray.”1 Higher increases (15%-16% per gray) were noted in the first 9 years after radiation therapy (RT), a finding recently independently reported by van den Bogaard et al.2 In our opinion, these studies may overstate the dose-dependence of RT-associated cardiac injury, particularly at low total doses.

Validation of an Accelerated Diagnostic Protocol for Aboriginal and Torres Strait Islander Patients with Suspected Acute Coronary Syndrome

Introduction: Aboriginal and Torres Strait Islander (ATSI) people have a high burden of cardiovascular disease. Observed rates of major coronary events are seven to nine times higher in people aged < 45 years for this population when compared with non-Indigenous Australians. The Improved Assessment of Chest Pain Trial (ImpACT) protocol is an evidenced-based ADP, which combines sensitive troponin testing, objective testing and clinical criteria, including age, to identify patients at high, intermediate or low risk of acute coronary syndrome (ACS). The Accelerated Chest Pain Risk Evaluation (ACRE) project is currently implementing the ImpACT protocol into public hospitals across Queensland. Aboriginal and Torres Strait Islander patients were under-represented in the original ImpACT study.

Lipoprotein(a) and the risk of cardiovascular disease in the European population: results from the BiomarCaRE consortium.

AimsAs promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the need for a precise characterization and comparability of the Lp(a)-associated cardiovascular risk is increasing. Therefore, we aimed to evaluate the distribution of Lp(a) concentrations across the European population, to characterize the association with cardiovascular outcomes and to provide high comparability of the Lp(a)-associated cardiovascular risk by use of centrally determined Lp(a) concentrations.Methods and resultsBased on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 56 804 participants from 7 prospective population-based cohorts across Europe with a maximum follow-up of 24 years. All Lp(a) measurements were performed in the central BiomarCaRE laboratory (Biokit Quantia Lp(a)-Test; Abbott Diagnostics). The three endpoints considered were incident major coronary events (MCE), incident cardiovascular disease (CVD) events, and total mortality. We found lower Lp(a) levels in Northern European cohorts (median 4.9 mg/dL) compared to central (median 7.9 mg/dL) and Southern European cohorts (10.9 mg/dL) (Jonckheere–Terpstra test P < 0.001). Kaplan–Meier curves showed the highest event rate of MCE and CVD events for Lp(a) levels ≥90th percentile (log-rank test: P < 0.001 for MCE and CVD). Cox regression models adjusted for age, sex, and cardiovascular risk factors revealed a significant association of Lp(a) levels with MCE and CVD with a hazard ratio (HR) of 1.30 for MCE [95% confidence interval (CI) 1.15‒1.46] and of 1.25 for CVD (95% CI 1.12‒1.39) for Lp(a) levels in the 67‒89th percentile and a HR of 1.49 for MCE (95% CI 1.29‒1.73) and of 1.44 for CVD (95% CI 1.25‒1.65) for Lp(a) levels ≥ 90th percentile vs. Lp(a) levels in the lowest third (P < 0.001 for all). There was no significant association between Lp(a) levels and total mortality. Subgroup analysis for a continuous version of cube root transformed Lp(a) identified the highest Lp(a)-associated risk in individuals with diabetes [HR for MCE 1.31 (95% CI 1.15‒1.50)] and for CVD 1.22 (95% CI 1.08‒1.38) compared to those without diabetes [HR for MCE 1.15 (95% CI 1.08‒1.21; HR for CVD 1.13 (1.07–1.19)] while no difference of the Lp(a)- associated risk were seen for other cardiovascular high risk states. The addition of Lp(a) levels to a prognostic model for MCE and CVD revealed only a marginal but significant C-index discrimination measure increase (0.001 for MCE and CVD; P < 0.05) and net reclassification improvement (0.010 for MCE and 0.011 for CVD).ConclusionIn this large dataset on harmonized Lp(a) determination, we observed regional differences within the European population. Elevated Lp(a) was robustly associated with an increased risk for MCE and CVD in particular among individuals with diabetes. These results may lead to better identification of target populations who might benefit from future Lp(a)-lowering therapies.

Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis.

The comparative clinical benefit of nonstatin therapies that reduce low-density lipoprotein cholesterol (LDL-C) remains uncertain. To evaluate the association between lowering LDL-C and relative cardiovascular risk reduction across different statin and nonstatin therapies. The MEDLINE and EMBASE databases were searched (1966-July 2016). The key inclusion criteria were that the study was a randomized clinical trial and the reported clinical outcomes included myocardial infarction (MI). Studies were excluded if the duration was less than 6 months or had fewer than 50 clinical events. Studies of 9 different types of LDL-C reduction approaches were included. Two authors independently extracted and entered data into standardized data sheets and data were analyzed using meta-regression. The relative risk (RR) of major vascular events (a composite of cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, or stroke) associated with the absolute reduction in LDL-C level; 5-year rate of major coronary events (coronary death or MI) associated with achieved LDL-C level. A total of 312 175 participants (mean age, 62 years; 24% women; mean baseline LDL-C level of 3.16 mmol/L [122.3 mg/dL]) from 49 trials with 39 645 major vascular events were included. The RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C level was 0.77 (95% CI, 0.71-0.84; P < .001) for statins and 0.75 (95% CI, 0.66-0.86; P = .002) for established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe) (between-group difference, P = .72). For these 5 therapies combined, the RR was 0.77 (95% CI, 0.75-0.79, P < .001) for major vascular events per 1-mmol/L reduction in LDL-C level. For other interventions, the observed RRs vs the expected RRs based on the degree of LDL-C reduction in the trials were 0.94 (95% CI, 0.89-0.99) vs 0.91 (95% CI, 0.90-0.92) for niacin (P = .24); 0.88 (95% CI, 0.83-0.92) vs 0.94 (95% CI, 0.93-0.94) for fibrates (P = .02), which was lower than expected (ie, greater risk reduction); 1.01 (95% CI, 0.94-1.09) vs 0.90 (95% CI, 0.89-0.91) for cholesteryl ester transfer protein inhibitors (P = .002), which was higher than expected (ie, less risk reduction); and 0.49 (95% CI, 0.34-0.71) vs 0.61 (95% CI, 0.58-0.65) for proprotein convertase subtilisin/kexin type 9 inhibitors (P = .25). The achieved absolute LDL-C level was significantly associated with the absolute rate of major coronary events (11 301 events, including coronary death or MI) for primary prevention trials (1.5% lower event rate [95% CI, 0.5%-2.6%] per each 1-mmol/L lower LDL-C level; P = .008) and secondary prevention trials (4.6% lower event rate [95% CI, 2.9%-6.4%] per each 1-mmol/L lower LDL-C level; P < .001). In this meta-regression analysis, the use of statin and nonstatin therapies that act via upregulation of LDL receptor expression to reduce LDL-C were associated with similar RRs of major vascular events per change in LDL-C. Lower achieved LDL-C levels were associated with lower rates of major coronary events.

Cardiac dose reduction during tangential breast irradiation using deep inspiration breath hold: a dose comparison study based on deformable image registration.

BackgroundRadiation therapy (RT) for a left-sided breast cancer often involves some incidental exposure of the heart and increase in the rate of major coronary events. One method to reduce the dose to the heart during a tangential breast irradiation is the deep inspiration breath hold (DIBH) technique. Our department adopted DIBH for selected left breast cancer patients with a maximum cardiac distance ≥ 10 mm. We evaluated the effect of the DIBH on cardiac dose compared to normal free breathing (FB). The secondary objective of our present study was to use modeled risk estimates to quantify the risk of coronary events after RT with DIBH.Methods and materialsThirty-two patients who underwent RT with DIBH at our hospital were retrospectively analyzed. For each patient, two computed tomography (CT) scans were acquired, FB-CT and DIBH-CT. Using a deformable image registration tool, the target volume was deformed from DIBH-CT to FB-CT, and conventional tangential treatment planning was performed, focusing on the equality of target coverage between the two plans. Doses to the heart, left anterior descending (LAD) artery, and ipsilateral lung were assessed.ResultsBy using DIBH, the average mean heart dose was reduced from 724.1 cGy to 279.3 (p < 0.001). The relative heart volume irradiated with 10 Gy–50 Gy was consistently reduced. The mean dose to the LAD coronary artery was reduced from 4079.1 cGy to 2368.9 cGy (p < 0.001). The ipsilateral lung volume receiving 20 Gy or more and 40 Gy or more was reduced by 2.2 % in both cases. Estimated risks of coronary events at 10 years were 4.03 and 2.55 % for RT with FB and DIBH, respectively (p < 0.001).ConclusionsThe use of DIBH during RT of the left-sided breast considerably reduces the doses delivered to the heart and LAD artery with similar target coverage. For the current study patients, the probability of major coronary events was reduced with DIBH.

Abstract ES4-1: Which patients can safely avoid radiation after breast conserving surgery?

Abstract Whether or not there is a subgroup of patients from whom adjuvant RT can be safely omitted after breast conserving surgery (BCS) for invasive breast cancer (IBC) remains controversial. The Oxford overview (1) shows that whole breast RT (WBRT) after BCS for IBC halves the risk of first recurrence. However the absolute reduction in ipsilateral breast tumour recurrence (IBTR) in ER+ older patients is modest.Guidelines on the omission of RT after BCS vary. The issue is complicated by falling IBTR rates after BCS, adjuvant endocrine therapy (AET) and RT, now around 2-3% at 5 years. The CALGB 9343 trial in women with T1, ER+ tumours receiving tamoxifen and randomized to WBRT or not showed a 3% reduction in local recurrence at 5 years from RT (1% vs 4%,p=&amp;lt;0.001) [2] At a median follow up of 10.5 years the difference in local recurrence had widened in favour of RT (2% RT+, 9% RT-)[3].The PRIME 2 trial randomised 1326 patients with T1-T2 (up to 3cm), pNO, hormone receptor positive tumours =/&amp;gt;65 years after BCS and AET to WBRT or no WBRT. It showed a 2.8% reduction in IBTR from RT (4.1% vs 1.3%,p=0.002) at a median follow up of 5 years(4). An unplanned subgroup analysis by ER status showed a 2.1% reduction in local recurrence (1.2% RT+, 3.3% RT-) from RT but should be interpreted cautiously. However omission of WBRT might be discussed with such patients as an option. Modest absolute improvements in local control from WBRT have to be balanced against increased rates of major coronary events (5).The risk of IBTR is influenced by local therapy, systemic therapy and biology (6).To refine selection of low risk patients, molecular markers of low risk are needed. If molecular signatures of radiosensitivity for breast cancer (7) can be validated from mature RCTs of BCS +/RT, selection of patients cured by surgery and adjuvant endocrine therapy alone could be strengthened.

Darapladib for Preventing Ischemic Events in Stable Coronary Heart Disease

BackgroundElevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2.MethodsIn a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization).ResultsDuring a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02).ConclusionsIn patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.)

Abstract P5-14-13: An observational study using g-H2AX foci to investigate cardiac doses of radiation in women following adjuvant radiotherapy for breast cancer: External beam radiotherapy versus targeted intraoperative radiotherapy

Abstract Background External beam radiotherapy (EBRT) is the gold standard adjuvant treatment after breast conserving surgery for localised breast cancer. A recent phase 3 trial has shown the non-inferiority of intraoperative radiotherapy (IORT) compared with EBRT in terms of short-term safety and efficacy (TARGIT A Trial; Lancet 2010). IORT also has advantages in cost saving and patient convenience. Radiation exposure of the heart and cardiac vessels is associated with an increase in morbidity and mortality following EBRT for breast cancer and has been shown to increase the rate of major coronary events by 7.4% per gray of exposure to the heart (Darby; NEJM 2013). IORT uses low energy x-rays (50 kV) and is likely to reduce the radiation exposure of the cardiovascular system compared with EBRT. We have used γ-H2AX foci formation in peripheral blood lymphocytes as a surrogate marker of radiation dose to the heart and great vessels. The phosphorylated histone H2AX protein (γ-H2AX) is expressed after induction of DNA double strand breaks caused by ionising radiation, created as the lymphocytes pass through and adjacent to the irradiated field. Methods 34 patients were recruited, having either EBRT or IORT as part of a randomised controlled trial. The main inclusion criteria were adult females with early breast cancer suitable for breast conserving surgery and the main exclusion criteria were previous malignancy, recent exposure to radiation (excluding CT planning scan) and prior chemotherapy. Blood samples were taken immediately prior to and 30 minutes after either first fraction of EBRT or after IORT treatment, and then rapidly processed to allow quantification of the γ-H2AX biomarker in lymphocytes (Rothkamm; Radiology 2007). This study had approval from the Local Research and Ethics Committee. Results Data were available for 31 patients. Means and standard deviations for the change in γ-H2AX foci number per cell for each group are summarised in table 1. Following IORT there was an increase of 0.203 foci per cell (range -1.436 to 1.275) compared with an increase of 0.935 foci per cell (range -0.679 to 2.216) in the EBRT group; this difference was highly significant (p = 0.009). Table 1: γ-H2AX foci per cell IORTEBRTMean0.2030.935SD0.6330.764n1318 Conclusions These data show a significantly greater change in γ-H2AX foci number per cell following one fraction of EBRT compared to IORT. IORT is a single treatment (20Gy at the applicator surface) whereas EBRT is repeated 15 times (2.67Gy x 15 fractions) multiplying the effect on the patients’ cardiovascular system. It may be hypothesised that this reduced radiotherapy dose from IORT will reduce the risk of cardiovascular morbidity and mortality compared to EBRT. This is the first study to demonstrate the real time effect of radiotherapy to the heart and great vessels using a biomarker and demonstrates a proof of concept methodology for similar applications. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-13.

Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer

BackgroundRadiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain.MethodsWe conducted a population-based case–control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart.ResultsThe overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy.ConclusionsExposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.)

Abstract 18079: Among CHD Patients in the IDEAL Study, Those with Elevated Levels of Alanine Aminotransferase at Baseline Had a Lower Rate of Major Coronary Events

Background: Previous evidence suggests that statin therapy can reduce cardiovascular (CV) morbidity in patients with mild-to-moderately abnormal liver tests. In this post hoc analysis of the IDEAL study, we investigated the relationship of elevated baseline levels of the liver enzyme alanine aminotransferase (ALT) on CV events, and compared the effects of atorvastatin (ATV) 80 mg versus simvastatin (SIM) 20-40 mg in patients with normal and elevated baseline ALT levels. Methods: IDEAL was a large randomized trial comparing ATV 80 mg with SIM 20-40 mg in 8888 patients with CHD over 4.8 years of follow-up. Cox regression analysis was performed to investigate the relationship of normal levels of ALT (defined as baseline ALT &lt;ULN [upper limit of normal]; 87.8% of subjects) vs elevated ALT (baseline ALT ≥ULN; 11.5% of subjects had ALT ≥ULN-&lt;2 ULN and 0.74% had ALT ≥2 ULN-&lt;3 ULN) on the risk of major coronary events (MCE: CHD death, non-fatal MI or resuscitated cardiac arrest). In addition, treatment effect (ATV 80mg vs SIM 20-40 mg) was examined for subjects with normal and elevated ALT at baseline. Results: Over the course of the study, mean ALT levels increased among patients with normal baseline ALT (n=7782) and decreased for those with ALT ≥ULN at baseline (n=1081). Overall, those patients with normal ALT levels at baseline experienced significantly more MCE than patients with higher baseline ALT levels (≥ULN) (HR=0.76; 95% CI 0.61, 0.96; p=0.02). This finding was consistent in patients treated with ATV (HR=0.60; 95% CI 0.42, 0.87; p=0.007) but not those receiving SIM (p=0.464). In patients with elevated ALT baseline levels, ATV significantly reduced the risk of MCE compared with SIM (HR=0.62; 95% CI 0.40, 0.96; p=0.03), but in patients with normal baseline ALT the difference between treatment groups did not reach statistical significance. Conclusions: In the overall population of CHD patients treated with ATV or SIM, those with normal baseline ALT levels experienced significantly more MCE than those with baseline ALT ≥ULN. The clinical benefits of intensive lipid lowering with ATV compared with a more moderate regimen with SIM were generally greater in patients with abnormal liver tests than in patients with normal liver tests.

Coronary Heart Disease Risk in Patients With Stroke or Transient Ischemic Attack and No Known Coronary Heart Disease

Noncoronary forms of atherosclerosis (including transient ischemic attacks or stroke of carotid origin or >50% stenosis of the carotid artery) are associated with a 10-year vascular risk of >20% and are considered as a coronary heart disease (CHD) -risk equivalent from the standpoint of lipid management. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial included patients with stroke or transient ischemic attack and no known CHD regardless of the presence of carotid atherosclerosis. We evaluated the risk of developing clinically recognized CHD in SPARCL patients. A total of 4731 patients (mean age, 63 years) was randomized to 80 mg/day atorvastatin placebo. The rates of major coronary event, any CHD event, and any revascularization procedure were evaluated. After 4.9 years of follow-up, the risks of a major coronary event and of any CHD end point in the placebo group were 5.1% and 8.6%, respectively. The rate of outcome of stroke decreased over time, whereas the major coronary event rate was stable. Relative to those having a large vessel-related stroke at baseline, those having a transient ischemic attack, hemorrhagic stroke, small vessel stroke, or a stroke of unknown cause had similar absolute rates for a first major coronary event and for any CHD event; transient ischemic attack, small vessel, and unknown cause groups had lower absolute revascularization procedure rates. Major coronary event, any CHD event, and any revascularization procedure rates were similarly reduced in all baseline stroke subtypes in the atorvastatin arm compared with placebo with no heterogeneity between groups. CHD risk can be substantially reduced by atorvastatin therapy in patients with recent stroke or transient ischemic attack regardless of stroke subtype.

Ankle Brachial Index Combined With Framingham Risk Score to Predict Cardiovascular Events and Mortality

Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Cardiovascular risk assessment in the metabolic syndrome: results from the Prospective Cardiovascular Munster (PROCAM) Study

We aimed (1) to construct a modified PROCAM risk algorithm, which incorporates BMI/waist circumference in a model for predicting coronary events; (2) to evaluate how accurate this and the previously established PROCAM risk algorithm predict coronary risk in individuals with metabolic syndrome. Prospective Cardiovascular Münster (PROCAM) Study, a prospective study of men and women at work in the northwest of Germany. A total of 7134 men aged 35-65 years at study entry. On the basis of 404 major coronary events (defined as nonfatal MI and coronary deaths), which occurred within 10 years of follow-up, a modified PROCAM risk algorithm was constructed by incorporating BMI/waist circumference as fixed variable in a Cox proportional hazards model for predicting coronary events. The metabolic syndrome was defined according to the latest recommendations proposed by the NCEP-ATP III Panel. Men who were classified as having the metabolic syndrome (n=2325, prevalence: 32.6%) were 2.59-fold more likely to experience a major coronary event within 10 years of follow-up than men not having the metabolic syndrome. In men with metabolic syndrome, the observed major coronary event rate of 9.6% corresponded well with their estimated global risk according to the modified BMI-based PROCAM risk algorithm (10.2%). Comparative calculations performed with the previously published fully adjusted PROCAM algorithm yielded very similar results. Both PROCAM algorithms provide very accurate means to ascertain coronary risk in male patients with metabolic syndrome.

Treatment of dyslipidemia in patients with type 2 diabetes: Overview and meta-analysis of randomized trials

Dyslipidemia in type 2 diabetes is characterized by high plasma triglyceride and decreased HDL cholesterol levels, as well as by predominance of small, dense LDL particles. Furthermore, the majority of patients with diabetes have higher than recommended LDL cholesterol levels. Several clinical randomized trials reviewed in this article shown benefit of statin treatment in primary and secondary prevention in patients with diabetes. We performed a meta-analysis of six secondary prevention trials with statins. Overall, a significant reduction in major coronary events (death from coronary artery disease or non-fatal myocardial infarction) by 22% was observed in these studies. Meta-analysis of four studies, which included patients without previous cardiovascular disease, shown also highly significant 32% reduction in the rate of major coronary events. Significant benefit of statin treatment was showed also in the meta-analysis of four trials, in which LDL cholesterol of ≤2.0 mmol/l was achieved in actively or aggressively treated group. Evidence-base from the studies with fibrates is less conclusive, since it comes from subgroup analysis of two trials, which included higher number of patients with diabetes. In both trials final triglyceride level of ≤1.5 mmol/l was achieved. Based on the above-mentioned evidence, all patients with diabetes should be treated with statins to achieve LDL cholesterol level ≤2.0 mmol/l. A secondary goal of triglyceride level ≤1.5 mmol/l is also reasonable to achieve. Achieving of both goals may warrant combination of statin treatment with fibrate, ezetimibe or niacin. However, results of no endpoint study with lipid lowering combination treatment have been published thus far.

Simvastatin for Secondary Prevention of All-Cause Mortality and Major Coronary Events in Patients With Mild Chronic Renal Insufficiency

A potentially modifiable risk factor for cardiovascular disease in patients with mild chronic renal insufficiency is dyslipidemia. Few studies examined the effects of statins on all-cause mortality and major coronary events in patients with renal dysfunction. We performed a post hoc analysis from the Randomized Trial of Cholesterol Lowering in 4,444 Patients with Coronary Heart Disease: The Scandinavian Simvastatin Survival Study. Of 4,444 participants, 2,314 (52.1%) had mild chronic renal insufficiency defined as an estimated glomerular filtration rate less than 75 mL/min/1.73 m(2) (<1.25 mL/s), measured using the Modification of Diet in Renal Disease equation. The primary end point was all-cause mortality. During the follow-up period, simvastatin use was associated with decreased all-cause mortality (adjusted hazard ratio [HR], 0.69; confidence interval [CI], 0.54 to 0.89) in the 2,314 participants with mild chronic renal insufficiency. Rates of major coronary events (adjusted HR, 0.67; CI, 0.56 to 0.79) and coronary revascularization (adjusted HR, 0.62; CI, 0.49 to 0.77) also were significantly lower in the simvastatin group. No significant decreases in stroke incidence were observed in the simvastatin group (adjusted HR, 0.88; CI, 0.55 to 1.39). The side-effect profile was similar between the 2 treatment groups. Simvastatin therapy appears to be effective and safe for the secondary prevention of all-cause mortality and major coronary events in patients with mild chronic renal dysfunction.

Statin Therapy and the Elderly

In the United States, the prevalence of coronary and other cardiovascular diseases increases with age, reflecting in part the cumulative effect of lifetime exposure to cardiovascular risk factors.1 Coronary and cerebrovascular atherosclerosis in the elderly (≥65 years of age) is a growing clinical problem because of the population’s increasing longevity. Despite this evidence, cardiovascular risk in elderly patients is demonstrably undermanaged according to several epidemiological studies.2–4 In a Canadian study, paradoxically, elderly coronary patients who were at the highest risk for recurrent disease appeared to be the least likely to receive preventive treatment.4 Several factors may contribute to this poor level of management, such as confusion surrounding the relevance of certain modifiable risk factors to this age group, the cost-effectiveness of preventing coronary heart disease (CHD) in older patients, and concerns about the impact of therapies on safety and quality of life. Article p 700 Despite early studies that questioned the association of cholesterol with coronary risk in the elderly, the available epidemiology now favors the perspective that cholesterol remains an important modifiable risk factor in patients ≥65 years of age, especially after adjustment for the presence of comorbid conditions.5 Growing evidence demonstrates the benefit of treating higher-risk older patients. In this issue of Circulation , Deedwania et al6 present the results of the Study Assessing Goals in the Elderly (SAGE), which compares the effect of intensive (atorvastatin 80 mg/d) compared with moderate (pravastatin 40 mg/d) cholesterol lowering with statins in a cohort of 893 men and women 65 to 85 years of age with coronary artery disease. SAGE evaluated the absolute change in total duration of ischemia as measured by 48-hour Holter monitoring from baseline to 1 year. Although total ischemia duration was reduced significantly in both arms compared with baseline, the intensive strategy …

Trends in rates of different forms of diagnosed coronary heart disease, 1978 to 2000: prospective, population based study of British men

Objective To examine trends over time in rates of different forms of diagnosed coronary heart disease among British men, during a period in which mortality due to coronary heart disease...

Primary Cardiovascular Events and Serum Lipid Levels in Elderly Japanese with Hypercholesterolemia Undergoing 6‐Year Simvastatin Treatment: A Subanalysis of the Japan Lipid Intervention Trial

To determine the relationship between serum lipid levels and the incidence of coronary events in older Japanese hypercholesterolemic patients without prior coronary heart disease (CHD). Post hoc subanalysis of the results in the Japan Lipid Intervention Trial. A large-scale cohort observational study conducted throughout Japan. Men aged 35 to 70 and postmenopausal women younger than 70 with serum total cholesterol (TC) level of 220 mg/dL or greater treated for 6 years with low-dose simvastatin (52,421 total patients). After exclusion of 5,127 patients because of prior CHD and 4,934 patients because of incomplete data, 42,360 patients were divided into an older (9,860 patients, aged 65-70, mean age 67.1) and younger (32,500 patients, younger than 65, mean age 54.9) group and analyzed. Fasting serum lipid levels were measured every 6 months. Major coronary events, including fatal or nonfatal myocardial infarction, and sudden cardiac death as the primary endpoint and other cardiovascular diseases, including onset of angina pectoris, cerebrovascular events, and any causes of death, as the secondary endpoints were monitored. Simvastatin treatment in older patients was as safe and effective as in younger patients. Incident rates of major coronary events were 1.30 per 1,000 patient-years in the older group and 0.80 per 1,000 patient-years in the younger group. The incidence of a major coronary event was correlated to serum TC and low-density lipoprotein cholesterol (LDL-C) levels in both groups. The absolute risk of major coronary events in the older group was higher than in the younger group at any level of LDL-C, whereas the relative risk increased by 1.7% with an elevation of each 1 mg/dL LDL-C level in both groups. In the older group, the risk of major coronary events also increased as triglyceride level increased, whereas the risk decreased as high-density lipoprotein cholesterol level increased above 60 md/dL. The LDL-C level-dependent increase of relative risk of CHD was similar in elderly and younger patients, whereas the absolute risk at any LDL-C level in elderly patients was higher than in younger patients.

Comparison of TIMI Frame Count and TIMI Myocardial Perfusion Grade in Assessment of Myocardial Reperfusion after Primary Angioplasty for Acute Myocardial Infarction

Background and Objectives:The eventual goal of reperfusion therapy, for an acute myocardial infarction (MI), is rapid and complete reperfusion into the myocardium beyond the epicardial artery. The recently designed TIMI frame count (TFC) and myocardial perfusion grade (TMPG) can be used to define the myocardial tissue perfusion. This study was undertaken to compare the TFC and TMPG for the assessment of myocardial reperfusion following primary angioplasty in patients with an acute anterior wall infarction. Subjects and Methods:33 patients, who admitted for acute myocardial infarction, between January 1998 and March 2001, were the subjects of this study. The subjects all underwent successful primary angioplasty on the LAD, with TIMI III flow. The ECGs, performed on admission and 1 hr after the angioplasty, were compared, the extent of the resolution of the ST elevation assessed. The TFC and TMPG were analyzed by 2 different observers using the coronary angiograms performed immediately and 7 days after the angioplasty. A retrospective analysis of the clinical events at the hospital, and the major coronary events during a follow-up of more than 6 months after discharge were performed. Results:The subjects were divided into 3 groups, completely recovered (n=11) and incompletely recovered (n=12) and not recovered (n=10), according to extent of the resolution of the ST elevation. There were no differences between the groups in their baseline characteristics. The TFC in the completely recovered group was significant lower (p=0.02, p=0.01) than the other patient groups immediately after the angioplasty, but there was no significant difference (p=0.28, p=0.32) in the TFC between the 3 patients groups 7 day after the angioplasty. The TMPG in the completely recovered group was consistently higher than in the other patient groups, both immediately and 7 days after the angioplasty. Five patients, who developed major coronary events during 16 month follow-up, tended to show no, or an incomplete resolution, of their ST elevation. They also showed significantly lower TMPG compared with the others, both immediately, and 7 days, after PTCA, but no significant difference at all in the TFC. Conclusion:The TMPG was closely associated with the rate of the ST elevation resolution in both the early and late periods after the primary angioplasty in acute MI, indicating that the TMPG is a better marker for the evaluation of myocardial reperfusion after primary angioplasty than the TFC. The low TMPG was observed to be related with a higher major coronary event rate, suggesting its usefulness as a predictor of long-term prognosis. (Korean Circulation J 2003;33 (10):864-870)