Carvedilol protects better against vascular events than metoprolol in heart failure: results from COMET.

OBJECTIVES: We explored whether vascular protection by carvedilol could contribute to its superior effects in the treatment of heart failure (HF) compared with metoprolol tartrate in the COMET (Carvedilol Or Metoprolol European Trial) study. BACKGROUND: Full adrenergic blockade by carvedilol and additional (e.g., antioxidative) properties may lead to vascular protection relative to beta-1 blockade alone, and contribute to its efficacy in HF treatment. METHODS: Three thousand twenty-nine patients with HF due to ischemic (51%) or idiopathic cardiomyopathy (44%) were randomized double-blind to carvedilol (n = 1,511) or metoprolol (n = 1,518) and followed for 58 months. Vascular end points were cardiovascular death, stroke, stroke death, myocardial infarction (MI), and unstable angina. RESULTS: The effect of carvedilol on cardiovascular death improved consistently in subgroups with prespecified baseline variables. Myocardial infarctions were reported in 69 carvedilol and 94 metoprolol patients (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52 to 0.97, p = 0.03). Cardiovascular death or nonfatal MI combined were reduced by 19% in carvedilol (HR 0.81, 95% CI 0.72 to 0.92, p = 0.0009 vs. metoprolol). Unstable angina was reported as an adverse event in 56 carvedilol and in 77 metoprolol patients (HR 0.71, 95% CI 0.501 to 0.998, p = 0.049). A stroke occurred in 65 carvedilol and 80 metoprolol patients (HR 0.79, 95% CI 0.57 to 1.10). Stroke or MI combined occurred in 130 carvedilol and 168 metoprolol patients (HR 0.75, 95% CI 0.60 to 0.95, p = 0.015), and fatal MI or fatal stroke occurred in 34 carvedilol and in 72 metoprolol patients (HR 0.46, 95% CI 0.31 to 0.69, p = 0.0002). Death after a nonfatal MI or stroke occurred in 61 of 124 carvedilol and in 106 of 160 metoprolol patients (HR 0.66, 95% CI 0.48 to 0.90, p = 0.0086). CONCLUSIONS: Carvedilol improves vascular outcomes better than metoprolol. These results suggest a ubiquitous protective effect of carvedilol against major vascular events.     

High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke

BACKGROUND: Inflammatory markers have been associated with ischemic stroke risk and prognosis after cardiac events. Their relationship to prognosis after stroke is unsettled. METHODS: A population-based study of stroke risk factors in 467 patients with first ischemic stroke was undertaken to determine whether levels of high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A(2) (Lp-PLA2) predict risk of stroke recurrence, other vascular events, and death. RESULTS: Levels of Lp-PLA2 and hs-CRP were weakly correlated (r = 0.09; P = .045). High-sensitivity CRP, but not Lp-PLA2, was associated with stroke severity. After adjusting for age, sex, race and ethnicity, history of coronary artery disease, diabetes mellitus, hypertension, hyperlipidemia, atrial fibrillation, smoking, and hs-CRP level, compared with the lowest quartile of Lp-PLA2, those in the highest quartile had an increased risk of recurrent stroke (adjusted hazard ratio, 2.08; 95% confidence interval, 1.04-4.18) and of the combined outcome of recurrent stroke, MI, or vascular death (adjusted hazard ratio, 1.86; 95% confidence interval, 1.01-3.42). After adjusting for confounders, hs-CRP was not associated with risk of recurrent stroke or recurrent stroke, myocardial infarction, or vascular death but was associated with risk of death (adjusted hazard ratio, 2.11; 95% confidence interval, 1.18-3.75). CONCLUSIONS: Inflammatory markers are associated with prognosis after first ischemic stroke and may offer complementary information. Lipoprotein-associated phospholipase A(2) may be a stronger predictor of recurrent stroke risk. Levels of hs-CRP, an acute-phase reactant, increase with stroke severity and may be associated with mortality to a greater degree than recurrence.     

Carotid wall thickness and stroke risk in patients with asymptomatic internal carotid stenosis

Objective

Aim of this study was to investigate if the risk of stroke and other vascular diseases can be predicted in subjects with severe asymptomatic carotid artery stenosis on the basis of carotid wall thickness evaluation.

Methods

We included 162 consecutive subjects with asymptomatic internal carotid artery stenosis of 60% or greater reduction in diameter. Demographic characteristics, vascular risk factors, therapy, degree of carotid stenosis and carotid intima–media thickness (IMT) were detailed for all subjects. Subjects were prospectively evaluated for a median period of 35 months (min = 10, max = 47). Outcome measures were: the occurrence of ischemic stroke ipsilateral to carotid stenosis and any other vascular event.

Results

Thirty subjects (18.5%) suffered a vascular event: 16 (53%) myocardial infarctions and 14 (47%) strokes. Older age and higher IMT values were the only factors significantly associated with the risk of vascular events. The hazard ratio (adjusted for age, sex and other risk factors) for each 0.1 mm of IMT increase resulted 1.30 (95% CI: 1.14, 1.18) for combined vascular events, 1.47 for cerebrovascular events (95% CI: 1.16, 1.87) and 1.24 (95% CI: 1.09, 1.42) for cardiovascular events. Values of IMT above 1.15 mm increased the risk of having a stroke 19 times and the risk of having a myocardial infarction two times.

Conclusions

An increased carotid wall thickness can be considered as a marker of an increased risk of vascular events in asymptomatic subjects with internal carotid artery stenosis >60%. Highest IMT values are able to identify subjects with specific stroke risk. This information could be of interest to recognize subjects who might benefit most from surgical or revascularization procedures.     

Hemostatic factors as predictors of stroke and cardiovascular diseases: the FINRISK '92 Hemostasis Study.

We carried out a prospective cohort study to determine whether the plasma levels of fibrinogen, plasminogen, factor VII and lipoprotein (a) are predictors of ischemic stroke and all cardiovascular disease (CVD) events. The FINRISK '92 Hemostasis Study included a random sample of 2372 participants, who were followed-up from winter 1992 to 31 December 2001. During the follow-up, 75 ischemic stroke and 145 coronary events occurred. Of these, 169 were observed among participants free of known CVD at baseline. In this group, fibrinogen and plasminogen were positively associated with the risk of a CVD event with hazard ratios of 1.22 [95% confidence interval (CI), 1.05-1.41] and 1.22 (95% CI, 1.03-1.44), respectively, after adjusting for age, sex and conventional risk factors. Factor VII:C was associated with risk of a future CVD event only among persons with positive history of CVD at baseline (hazard ratio, 1.32; 95% CI, 1.00-1.73). Factor VII antigen was not associated with CVD risk. None of the measured hemostatic factors was a predictor of ischemic stroke events, with the possible exception of lipoprotein (a), which had a borderline significant association (hazard ratio, 1.25; 95% CI, 0.99-1.58). In conclusion, the present study supports the observations that fibrinogen and plasminogen are significant predictors of CVD events, independently of conventional risk factors.     

Thirty-year risk of ischemic stroke in individuals with sickle cell trait and modification by chronic kidney disease: The atherosclerosis risk in communities (ARIC) study

Sickle cell trait (SCT) has been associated with hypercoagulability, chronic kidney disease (CKD), and ischemic stroke. Whether concomitant CKD modifies long-term ischemic stroke risk in individuals with SCT is uncertain. We analyzed data from 3602 genotyped black adults (female = 62%, mean baseline age = 54 years) who were followed for a median 26 years by the Atherosclerosis Risk in Communities Study. Ischemic stroke was verified by physician review. Associations between SCT and ischemic stroke were analyzed using repeat-events Cox regression, adjusted for potential confounders. SCT was identified in 236 (7%) participants, who more often had CKD at baseline than noncarriers (18% vs 13%, P = .02). Among those with CKD, elevated factor VII activity was more prevalent with SCT genotype (36% vs 22%; P = .05). From 1987-2017, 555 ischemic strokes occurred in 436 individuals. The overall hazard ratio of ischemic stroke associated with SCT was 1.31 (95% CI: 0.95-1.80) and was stronger in participants with concomitant CKD (HR = 2.18; 95% CI: 1.16-4.12) than those without CKD (HR = 1.09; 95% CI: 0.74-1.61); P for interaction = .04. The hazard ratio of composite ischemic stroke and/or death associated with SCT was 1.20 (95% CI: 1.01-1.42) overall, 1.44 (95% CI: 1.002-2.07) among those with CKD, and 1.15 (95% CI: 0.94-1.39) among those without CKD; P for interaction = .18. The long-term risk of ischemic stroke associated with SCT relative to noncarrier genotype appears to be modified by concomitant CKD.     

Patent foramen ovale and the risk of ischemic stroke in a multiethnic population.

OBJECTIVES: We sought to assess the risk of ischemic stroke from a patent foramen ovale (PFO) in the multiethnic prospective cohort of northern Manhattan. BACKGROUND: Patent foramen ovale has been associated with increased risk of ischemic stroke, mainly in case-control studies. The actual PFO-related stroke risk in the general population is unclear. METHODS: The presence of PFO was assessed at baseline by using transthoracic 2-dimensional echocardiography with contrast injection in 1,100 stroke-free subjects older than 39 years of age (mean age 68.7 +/- 10.0 years) from the Northern Manhattan Study (NOMAS). The presence of atrial septal aneurysm (ASA) also was recorded. Subjects were followed annually for outcomes. We assessed PFO/ASA-related stroke risk after adjusting for established stroke risk factors. RESULTS: We detected PFO in 164 subjects (14.9%); ASA was present in 27 subjects (2.5%) and associated with PFO in 19 subjects. During a mean follow-up of 79.7 +/- 28.0 months, an ischemic stroke occurred in 68 subjects (6.2%). After adjustment for demographics and risk factors, PFO was not found to be significantly associated with stroke (hazard ratio 1.64, 95% confidence interval [CI] 0.87 to 3.09). The same trend was observed in all age, gender, and race-ethnic subgroups. The coexistence of PFO and ASA did not increase the stroke risk (adjusted hazard ratio 1.25, 95% CI 0.17 to 9.24). Isolated ASA was associated with elevated stroke incidence (2 of 8, or 25%; adjusted hazard ratio 3.66, 95% CI 0.88 to 15.30). CONCLUSIONS: Patent foramen ovale, alone or together with ASA, was not associated with an increased stroke risk in this multiethnic cohort. The independent role of ASA needs further assessment in appositely designed and powered studies.     

Usefulness of right ventricular fractional area change to predict death, heart failure, and stroke following myocardial infarction (from the VALIANT ECHO Study)

Severe right ventricular dysfunction independent of left ventricular ejection fraction increased the risk of heart failure (HF) and death after myocardial infarction (MI). The association between right ventricular function and other clinical outcomes after MI was less clear. Two-dimensional echocardiograms were obtained in 605 patients with left ventricular dysfunction and/or clinical/radiologic evidence of HF from the VALIANT echocardiographic substudy (mean 5.0 +/- 2.5 days after MI). Clinical outcomes included all-cause mortality, cardiovascular (CV) death, sudden death, HF, and stroke. Baseline right ventricular function was measured in 522 patients using right ventricular fractional area change (RVFAC) and was related to clinical outcomes. Mean RVFAC was 41.9 +/- 4.3% (range 19.2% to 53.1%). The incidence of clinical events increased with decreasing RVFAC. After adjusting for 11 covariates, including age, ejection fraction, and Killip's classification, decreased RVFAC was independently associated with increased risk of all-cause mortality (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.31 to 1.98), CV death (HR 1.62, 95% CI 1.30 to 2.01), sudden death (HR 1.79, 95% CI 1.26 to 2.54), HF (HR 1.48, 95% CI 1.17 to 1.86), and stroke (HR 2.95, 95% CI 1.76 to 4.95), but not recurrent MI. Each 5% decrease in baseline RVFAC was associated with a 1.53 (95% CI 1.24 to 1.88) increased risk of fatal and nonfatal CV outcomes. In conclusion, decreased right ventricular systolic function is a major risk factor for death, sudden death, HF, and stroke after MI.     

beta1- and beta2-adrenergic receptor gene variation, beta-blocker use and risk of myocardial infarction and stroke

BACKGROUND: The benefits of beta-blocker therapy may depend on underlying genetic susceptibility. METHODS: We investigated the interaction of common variation in beta1 and beta2 adrenergic receptor (AR) genes with beta-blocker use on the risks of myocardial infarction (MI) and ischemic stroke in a case-control study. Participants were treated pharmacologically for hypertension, aged 30-79 years, with incident MI (n = 659) or ischemic stroke (n = 279) between 1995 and 2004, and 2,249 matched controls. RESULTS: We observed an interaction of beta-blocker use with beta1-AR gene variation on MI risk (P value, 6 degrees of freedom: 0.01) and ischemic stroke risk (P value, 6 degrees of freedom: 0.04). Compared with use of other antihypertensive medications, beta-blocker use was associated with higher MI risk in carriers of one or two copies of rs#17875422 (Odds ratio (OR): 2.66, 95% confidence interval (CI); 1.26-5.60) but not in homozygous carriers of the common allele (OR: 0.88, 95% CI: 0.73-1.07). Another variant, rs#2429511, interacted with beta-blocker use on both MI and ischemic stroke risks. beta-blocker use was associated with higher risk of combined MI and ischemic stroke in carriers of rs#2429511 (OR: 1.24, 95% CI: 1.03-1.50) but not in homozygous carriers of common allele (OR: 0.70, 95% CI: 0.51-0.94). beta-blocker use did not interact with beta2-AR gene variation on the risks of MI and ischemic stroke. CONCLUSIONS: These results, which require replication, suggest genetic variants in the beta1-AR gene may determine whether to use beta-blockers in hypertension for the primary prevention of cardiovascular disease.     

The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study

OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults. DESIGN: A prospective population-based study. SETTING: Four field centers in U.S. communities. PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later. MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides. RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality. CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.     

Predictors of outcome in stable outpatients with peripheral artery disease

Patients with peripheral artery disease (PAD) are at increased risk for subsequent ischemic events. We used data from the FRENA Registry to find predictors of subsequent myocardial infarction (MI), ischemic stroke, and limb amputation in stable outpatients with PAD. As of January 2012, 1,270 patients with PAD were recruited, of whom 1,042 (82 %) had Fontaine stage II; 113 (8.9 %) stage III; and 115 (9.1 %) stage IV. Over a mean follow-up of 14 months, 35 patients developed MI, 25 had stroke, 39 underwent limb amputation, and 91 died. Among patients with Fontaine stage II, the incidence of MI (2.09 events per 100 patient-years; 95 % CI 1.43–2.97) or stroke (0.93; 95 % CI 0.52–1.56) was similar to that of limb amputation (3.22; 95 % CI 2.37–4.29). On multivariate analysis, patients with diabetes [hazard ratio (HR) 2.09; 95 % CI 1.05–4.18], prior coronary disease (HR 5.35; 95 % CI 2.24–12.8), or atrial fibrillation (HR 3.11; 95 % CI 1.52–6.37) were at increased risk for MI; female (HR 2.94; 95 % CI 1.32–6.67), those with prior stroke (HR 5.21; 95 % CI 1.22–22.2) or atrial fibrillation (HR 3.37; 95 % CI 1.45–7.85) at increased risk for stroke; and female (HR 2.38; 95 % CI 1.23–4.55), those with diabetes (HR 3.50; 95 % CI 1.58–7.73) or advanced stages of PAD were at increased risk for limb amputation. Prior coronary artery disease, diabetes and atrial fibrillation predicted subsequent MI; female gender, prior stroke and atrial fibrillation predicted stroke; and female gender, diabetes, and advanced stages of PAD predicted limb amputation.     

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.     

Advanced chronic kidney disease,cardiovascular events and the effect of diabetes: data from the Atherosclerosis and Folic Acid Supplementation Trial

Background: End‐stage kidney disease registry data have reported increased mortality in patients with diabetes as compared with those without. Here we examine whether diabetes is independently associated with an increased risk of major cardiovascular events and death in patients with advanced chronic kidney disease (CKD). Methods: Data from 315 participants with CKD in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) were assessed. Primary end‐points were fatal or non‐fatal cardiovascular events, including myocardial infarction, stroke, unstable angina, coronary revascularisation and peripheral vascular events assessed both jointly and separately using Cox‐proportional hazard models. Results: Twenty‐three per cent reported diabetes. Median follow up was 3.6 years. In those with diabetes, an increased risk for major cardiovascular events was observed, crude hazard ratio (HR) 2.87 (95% confidence interval (CI) 2.11–3.90). After adjustment for age, gender, smoking, systolic blood pressure, body mass index, past ischaemic heart disease and use of preventive therapies, diabetes was associated with an HR of 1.83 (1.28–2.61) for major cardiovascular events. The risk for peripheral vascular events was also increased, adjusted HR 6.31 (2.61–15.25). For all‐cause death, major coronary and stroke events, the risk in those with diabetes was not significantly increased (all‐cause death, adjusted HR 1.31 (95% CI 0.80–2.14); major coronary events, adjusted HR 1.26 (95% CI 0.64–2.49); and major stroke events, adjusted HR 1.28 (95% CI 0.55–2.99)). Conclusions: Diabetes significantly increases the risk of major cardiovascular events, especially peripheral vascular events in patients with advanced CKD. Trials of multifactorial management of cardiovascular risk factors are required to determine if outcomes for this population may be improved.     

Long-Term Outcomes and Associations With Major Adverse Limb Events After Peripheral Artery Revascularization

BackgroundLong-term cardiovascular and limb outcomes after revascularization for peripheral artery disease and, in particular, prognosis after post-procedure major adverse limb events (MALE) are not well-studied.ObjectivesThis study sought to describe outcomes after peripheral revascularization and assess relationships between post-procedure MALE hospitalization and subsequent events.MethodsPatients undergoing peripheral artery revascularization between January 1, 2009, and September 30, 2015, in the Premier Healthcare Database were examined for the co-primary outcomes of interest, composite myocardial infarction (MI) or stroke and composite major amputation or peripheral revascularization. Multivariable adjusted Cox proportional hazards models with post-procedure MALE hospitalization included as a time-dependent covariate were developed to estimate hazard ratios for outcomes.ResultsAmong 393,017 revascularized patients followed for a median of 2.7 years (interquartile range: 1.3 to 4.4 years), the cumulative incidence of MI or stroke was 9.8% and that of major amputation or peripheral revascularization was 41.9%. A total of 50,750 patients (12.9%) had at least 1 post-procedure MALE hospitalization. In time-dependent covariate adjusted models, post-procedure MALE hospitalization was associated with greater risk of subsequent MI or stroke (hazard ratio: 1.34; 95% confidence interval: 1.28 to 1.40) and major amputation or peripheral revascularization (hazard ratio: 8.13; 95% confidence interval: 7.96 to 8.29). After peripheral revascularization with or without post-procedure MALE hospitalization, risk of limb events increased rapidly post-procedure and more slowly after the first year, whereas cardiac risk increased steadily during follow-up.ConclusionsRevascularized peripheral artery disease patients face earlier limb and later cardiovascular ischemic risk that is heightened among patients with post-procedure MALE hospitalization. Increased provider awareness of these long-term risks may guide efforts to improve post-procedural outcomes.     

The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study.

OBJECTIVES: We investigated the association between alcohol consumption and incident congestive heart failure (CHF) both overall and after adjusting for incident myocardial infarction (MI). BACKGROUND: Moderate alcohol consumption has been associated with lower risk of CHF and MI. METHODS: The Cardiovascular Health study, a prospective cohort study of cardiovascular disease risk factors and outcomes, followed 5,888 subjects > or =65 years old for 7 to 10 years. Cox models were used to estimate the adjusted risk of CHF by reported alcohol consumption. RESULTS: There were 5,595 subjects at baseline at risk for incident CHF with alcohol data and 1,056 events during follow-up. Compared with abstainers, the adjusted risk of CHF was lower among subjects who reported consuming 1 to 6 drinks per week (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.67 to 1.00, p = 0.05) and 7 to 13 drinks per week (HR 0.66, 95% CI 0.47 to 0.91, p = 0.01). Time-dependent adjustment for incident MI altered only slightly the association between moderate alcohol consumption and CHF (for 1 to 6 drinks per week, HR 0.84, 95% CI 0.65 to 1.04; for 7 to 13 drinks per week, HR 0.69, 95% CI 0.49 to 0.99). Baseline former drinkers had a higher risk of CHF than abstainers (HR 1.51, p < 0.01), but those who quit during the study did not have a higher risk (HR 0.83, 95% CI 0.66 to 1.03). CONCLUSIONS: Moderate alcohol use is associated with a lower risk of incident CHF among older adults, even after accounting for incident MI and other factors.     

Blood pressure level and outcomes in adults aged 65 and older with prior ischemic stroke

OBJECTIVES: To examine the association between blood pressure (BP) levels and long-term stroke outcomes in elderly stroke survivors. DESIGN: Observational study. SETTING: The Cardiovascular Health Study (CHS) of 5,888 community-dwelling adults. PARTICIPANTS: Two hundred fifty-four adults aged 65 and older (mean age 78.6) who sustained a nonfatal first ischemic stroke. MEASUREMENTS: BP levels assessed at prestroke and poststroke CHS visits were examined as predictors of stroke recurrence, coronary heart disease (CHD), combined vascular events (CVEs), and mortality. RESULTS: Higher poststroke BP level, assessed 261.6 days (mean) after stroke, was associated with higher risk of stroke recurrence over 5.4 years (mean) of follow-up. The multivariate-adjusted hazard ratio for stroke recurrence was 1.42 (95% confidence interval (CI) = 1.03-1.99) per standard deviation (SD) of systolic BP (P = .04) and 1.39 (95% CI = 1.01-1.91) per SD of diastolic BP (P = .04). Mortality was significantly greater in patients with low or high poststroke BP than in those with intermediate BP. Poststroke BP was not associated with risk of CHD or CVE, although further analyses suggested that high systolic BP predicted CHD and CVE in younger but not older subjects. Prestroke BP did not predict poststroke outcomes. CONCLUSION: In this observational study of adults aged 65 and older assessed approximately 8 months after stroke, low BP was associated with favorable risk of recurrent stroke, although high and low poststroke BP levels were associated with greater mortality. Long-term antihypertensive trials in older stroke survivors would increase knowledge about the benefits of lowering BP in this population.     

Aspirin for Primary Prevention of Cardiovascular Events

BackgroundThe efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable.ObjectivesThe purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data.MethodsRandomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.ResultsA total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.ConclusionsAspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.     

Prediction of intermittent claudication, ischemic stroke, and other cardiovascular disease by detection of abdominal aortic calcific deposits by plain lumbar radiographs

There has been little attention to vascular calcium testing for generalized assessment of cardiovascular disease (CVD) outcomes, such as intermittent claudication (IC) and ischemic stroke (IS). We hypothesize that aortic calcium is an important predictor of CVD outcomes. Lumbar x-rays were obtained in 848 men and 1,301 women (mean ages 59.7 and 60.1 years, respectively) from the original cohort of the Framingham Heart Study. Abdominal aortic calcium (AAC) deposits were graded using a previously validated scale. Participants were categorized according to a 10-year Framingham coronary heart disease (CHD) risk score. Multivariable Cox proportional hazards analyses were performed to relate AAC to CVD outcomes. There were 199 IC events, 201 IS events, 702 CHD events, and 1,121 CVD events during 32 years of follow-up. Multivariable adjusted hazard ratios for the third versus first AAC tertile in the combined cohort were 1.68 (95% confidence interval [CI] 1.12 to 2.50) for IC, 1.73 (95% CI 1.12 to 2.65) for IS, 1.59 (95% CI 1.26 to 2.00) for CHD, and 1.64 (95% CI 1.37 to 1.97) for CVD. Hazard ratios for IC and IS were similar in magnitude to those for CHD and CVD. A high AAC score was associated with significantly higher incidence of events in subjects at intermediate Framingham CHD risk for all end points. Risk prediction based on cardiovascular risk factors improved for most outcomes when AAC was added. In conclusion, there was a graded, increasing, and independent association of AAC with incident IC and IS, similar in magnitude to risks predicted for CHD and CVD. AAC appears to be useful for risk stratification in patients at intermediate CHD risk.     

Triglyceride-Rich Lipoprotein Cholesterol,Small Dense LDL Cholesterol,and Incident Cardiovascular Disease

BackgroundElevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease.ObjectivesThe purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD).MethodsIn a prospective case-cohort study within the Women’s Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein.ResultsThe risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]_Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; p_trend = 0.002; PAD HR_Q4: 2.58 [95% CI: 1.18 to 5.63]; p_trend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HR_Q4: 3.71 [95% CI: 1.59 to 8.63]; p_trend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl).ConclusionsTRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women’s Health Study; NCT00000479)     

Vascular surgery patients: perioperative and long-term risk according to the ACC/AHA guidelines, the additive role of post-operative troponin elevation.

AIMS: The objectives of this study are to evaluate the prognostic role of pre-operative stratification in patients undergoing elective major vascular surgery, the timing of adverse outcomes, and the predictive role of troponin (cTn). METHODS AND RESULTS: Consecutive vascular surgery candidates (n=391) were prospectively stratified and treated according to the ACC/AHA guidelines. The patients were categorized into three groups: (1) with coronary revascularization in the past 5 years, (2) with intermediate clinical risk predictors, and (3) with minor or no clinical risk predictors. cTnI was measured post-operatively. By 18 months, 18.7% of subjects had experienced death or acute myocardial infarction (MI) (by the ACC/ESC criteria). The hazard ratio (HR) was 5.21 (95% CI=2.60-10.43; P<0.0001) in group 1 and 2.58 (95% CI=1.27-4.38; P=0.004) in group 2 when compared with group 3. Most events occurred within 30 days. Elevations of cTnI were associated with adverse outcomes even after multivariable adjustment at long-term (adjusted overall HR=4.73, 95% CI=2.92-7.65; P<0.0001) and at 30 days (adjusted HR=5.52, 95% CI=3.23-9.42; P<0.0001). CONCLUSION: After pre-operative stratification, patients undergoing elective major vascular surgery remain at high risk of MI and death. Events occur mainly early after surgery. cTnI elevations are frequent and independently associated with increased risk. These findings suggest the need for a major re-evaluation of our approach to these patients.