Patients with significant coronary artery stenoses are at increased risk of future cardiac events. However, in the absence of acute coronary syndrome or recent myocardial infarction and residual ischemia, elective percutaneous coronary intervention has not been shown to improve prognosis. Possible explanations for this might be the limited follow-up time adopted by most randomized trials comparing percutaneous coronary intervention with medical therapy, limited number of patients with proven ischemia enrolled in these trials, and adoption of complex, elaborate techniques that have not proved their usefulness. Published evidence identifies certain indications for percutaneous coronary intervention in patients with stable coronary lesions: demonstration of significant inducible ischemia, particularly in the context of a recent myocardial infarction; detection of unequivocally reduced fractional flow reserve; and specific angiographic features of coronary stenoses. Operators should take into account long-term consequences of adopted techniques rather than immediate angiographic results. We review existing evidence and provide our recommendations in this setting.
]]>This study assessed the impact on long-term mortality of percutaneous coronary intervention (PCI) versus medical treatment in patients with symptoms or signs of myocardial ischemia but no acute coronary syndrome.
The impact of PCI on the long-term prognosis of patients with stable coronary artery disease has not been established.
We identified 17 randomized trials comparing a PCI-based invasive treatment strategy with medical treatment in 7,513 patients with symptoms or signs of myocardial ischemia but no acute coronary syndrome. Of these patients, 3,675 were assigned to the PCI group and 3,838 to the medical treatment group. The primary end point was all-cause death. The length of follow-up was in the range between 12 and 122 months, 51 months on average.
In the PCI group, 271 patients died compared with 335 patients in the medical treatment group, which corresponds to a 20% reduction in the odds ratio (OR) of all-cause death (OR: 0.80; 95% confidence interval [CI]: 0.64 to 0.99, p = 0.263 for heterogeneity across the trials). Allocation to the PCI group was associated with a nonsignificant 26% reduction in the OR of cardiac death (OR: 0.74, 95% CI: 0.51 to 1.06). In the PCI group, 319 patients had a nonfatal myocardial infarction after randomization compared with 357 patients in the medical treatment group (OR: 0.90, 95% CI: 0.66 to 1.23).
These findings suggest that a PCI-based invasive strategy may improve long-term survival compared with a medical treatment-only strategy in patients with stable coronary artery disease.
The authors of the meta-analysis of a percutaneous coronary intervention (PCI)-based invasive strategy for improving prognosis for the treatment of angina conclude that a pooling of data from various studies can be sufficiently powered to evaluate the impact of PCI on long-term mortality. However, most randomized coronary artery patient trials have insufficient power to detect significant differences in hard end points. Randomized trials in patients with chronic stable angina enroll few patients who are over age 65 years, have depressed ventricular function, have clinical instability, or who have undergone previous coronary artery bypass grafting (CABG) or PCI. "Medical therapy" today no longer means the absence of PCI, but rather the presence of intensive, evidence-based pharmacologic intervention. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial randomized 2,287 patients to optimal medical therapy alone or optimal medical therapy plus PCI. Optimal medical therapy consisted of antiplatelet therapy, anti-ischemic therapy, and aggressive lipid and blood pressure control. Based on the strength of the evidence, the author of this commentary recommends more-aggressive medical therapy for patients with moderate-to-severe angina, and PCI or CABG for many patients in whom symptoms persist. Optimal medical therapy is a proven option for chronic stable angina.
]]>This study was designed to establish the direct vascular effects of apelin in vivo in man.
Apelin is the endogenous ligand for the previously orphaned G-protein–coupled receptor, APJ. This novel pathway is widely expressed in the cardiovascular system and is emerging as an important mediator of cardiovascular homeostasis. In pre-clinical models, apelin causes venous and arterial vasodilation.
Vascular effects of apelin were assessed in 24 healthy volunteers. Dorsal hand vein diameter was measured by the Aellig technique during local intravenous infusions (0.1 to 3 nmol/min) of apelin-36, (Pyr1)apelin-13, and sodium nitroprusside (0.6 nmol/min). Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of apelin-36 and (Pyr1)apelin-13 (0.1 to 30 nmol/min) and subsequently in the presence or absence of a "nitric oxide clamp" (nitric oxide synthase inhibitor, L-N G-monomethylarginine [8 µmol/min], coinfused with nitric oxide donor, sodium nitroprusside [90 to 900 ng/min]), or a single oral dose of aspirin (600 mg) or matched placebo.
Although sodium nitroprusside caused venodilation (p < 0.0001), apelin-36 and (Pyr1)apelin-13 had no effect on dorsal hand vein diameter (p = 0.2). Both apelin isoforms caused reproducible vasodilation in forearm resistance vessels (p < 0.0001). (Pyr1)apelin-13–mediated vasodilation was attenuated by the nitric oxide clamp (p = 0.004) but unaffected by aspirin (p = 0.7).
Although having no apparent effect on venous tone, apelin causes nitric oxide–dependent arterial vasodilation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis.
This study sought to determine whether the benefit of intensive lipid-lowering therapy (LLT) is dependent on baseline low-density lipoprotein cholesterol (LDL-C).
Aggressive LDL-C reduction with statins improves cardiovascular outcomes in acute and chronic coronary heart disease (CHD). The importance of baseline LDL-C is unclear.
We compared 2-year composites of death, myocardial infarction (MI), unstable angina, revascularization >30 days, and stroke (primary end point), and CHD death, MI, and revascularization >30 days (secondary end point) in 2,986 statin-naïve patients with recent acute coronary syndrome (ACS) randomized to atorvastatin 80 mg versus pravastatin 40 mg in the PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) study stratified by quartiles of baseline LDL-C. Multivariable models assessed whether the treatment benefit was dependent on baseline LDL-C.
A significant reduction in the hazards of the primary (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.47 to 0.85, p = 0.002) and secondary (HR: 0.57, 95% CI: 0.42 to 0.79, p = 0.001) end points occurred in patients within the highest quartile (>132 mg/dl) of baseline LDL-C treated with atorvastatin 80 mg. The benefit of intensive therapy progressively declined as baseline LDL-C decreased. The lowest quartile (LDL-C ≤92 mg/dl) experienced similar rates of the primary (HR: 0.93, 95% CI: 0.69 to 1.25, p = 0.63) and secondary (HR: 0.98, 95% CI: 0.71 to 1.35, p = 0.89) end points. Adjusted interaction tests between treatment and highest versus lowest baseline LDL-C quartile were significant for the primary and secondary end points (p = 0.03 and p = 0.007, respectively). Analyzing baseline LDL-C as a continuous variable, atorvastatin 80 mg was associated with improved outcomes provided the baseline LDL-C was >66 mg/dl.
A progressive reduction in the benefit of intensive LLT with atorvastatin 80 mg over pravastatin 40 mg occurred in statin-naïve ACS patients as baseline LDL-C declined. (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 [PROVE IT–TIMI 22];
We sought to determine which surgical technique of left atrial appendage (LAA) closure is most successful by assessing them with transesophageal echocardiography (TEE).
Atrial fibrillation is a risk factor for stroke, with 90% of clots occurring in the LAA. Several surgical techniques of LAA closure are used to theoretically reduce the stroke risk, with varying success rates.
A total of 137 of 2,546 patients who underwent surgical LAA closure from 1993 to 2004 had a TEE after surgery. Techniques consisted of either excision or exclusion by sutures or stapling. The TEE measurements included color Doppler flow in the LAA and interrogation for thrombus. Patent LAA, remnant LAA (residual stump >1 cm), or excluded LAA with persistent flow into the LAA were identified as unsuccessful closure.
Of the 137 patients, 52 (38%) underwent excision and 85 (62%) underwent exclusion (73 suture and 12 stapler). Only 55 of 137 (40%) of closures were successful. Successful LAA closure occurred more often with excision (73%) than suture exclusion (23%) and stapler exclusion (0%) (p < 0.001). We found LAA thrombus to be present in 28 of 68 patients (41%) with unsuccessful LAA exclusion versus none with excision. At time of TEE, 6 patients with successful LAA closure (11%) and 12 with unsuccessful closure (15%) had evidence of stroke/transient ischemic attack (p = 0.61).
There is a high occurrence of unsuccessful surgical LAA closure. Of the various techniques, excision appears to be the most successful.
Our aim was to evaluate the impact of metabolic syndrome (MetS) on cardiac phenotype in adolescents.
A high prevalence of MetS has been reported in adolescents.
Four hundred forty-six nondiabetic American Indian adolescents (age 14 to 20 years, 238 girls) underwent clinical evaluation, laboratory testing, and Doppler echocardiography. Age- and gender-specific partition values were used to define obesity and hypertension. Metabolic syndrome was defined according to Adult Treatment Panel III criteria, modified for adolescents. Left ventricular (LV) hypertrophy and left atrial (LA) dilation were identified using age- and gender-specific partition values.
One hundred eleven participants met criteria for MetS. They had a similar age and gender distribution as non-MetS participants. Analysis of covariance, controlling for relevant confounders, demonstrated that participants with MetS had higher LV, LA, and aortic root diameters, higher LV relative wall thickness, and greater LV mass index. Accordingly, MetS participants showed higher prevalences of LV hypertrophy (43.2% vs. 11.7%) and LA dilation (63.1% vs. 21.9%, both p < 0.001) compared with non-MetS participants. In addition, MetS was associated with a reduction in midwall shortening, lower transmitral mitral early to atrial peak velocity ratio, and mildly prolonged mitral early deceleration time (all p < 0.05). In multiple regression analysis, independently of demographics, obesity, blood pressure, and single metabolic components of MetS, clustered MetS was associated with a 2.6-fold higher likelihood of LV hypertrophy and a 2.3-fold higher likelihood of LA dilation (both p ≤ 0.02).
In a population sample of adolescents, MetS is associated with higher prevalences of LV hypertrophy and LA dilation and with reduced LV systolic and diastolic function, independently of individual MetS components.
This study was designed to investigate whether single nucleotide polymorphisms (SNPs) and haplotypes of the fibrinogen gene-cluster (fibrinogen chains alpha [FGA], beta [FGB], and gamma [FGG]) could explain the inter- and intraindividual variability of fibrinogen levels in patients with atherosclerosis. We also searched for genetic determinants affecting the responses of fibrinogen genes to proinflammatory stimulation.
The mechanisms regulating fibrinogen levels are not fully understood, and they are likely to be regulated by complex gene–environment interactions.
In the AIRGENE study, 895 survivors of myocardial infarction from 5 European cities were followed prospectively for 6 to 8 months, and plasma fibrinogen, interleukin (IL)-6, and C-reactive protein levels were determined monthly. We analyzed 21 SNPs and the corresponding haplotypes in the 3 fibrinogen genes.
Eight SNPs in FGA and FGB were significantly associated with fibrinogen levels. Similarly, 2 different haplotypes in FGA and 3 in FGB were also associated with mean fibrinogen levels. The IL-6 levels had a significant impact on the associations between SNPs/haplotypes in FGA/FGB and fibrinogen levels. We also identified SNPs and haplotypes in FGA and FGB with strong impact on the intraindividual variability of fibrinogen during the follow-up period.
We identified common SNPs and haplotypes on FGA/FGB genes, explaining the interindividual and intraindividual variability of fibrinogen levels, in patients with a history of myocardial infarction. We have also identified for the first time, SNPs/haplotypes on FGA/FGB whose effects on fibrinogen expression are modified by the underlying IL-6 levels. These findings may have an impact on risk stratification and the design of genetically guided therapeutic approaches in patients with advanced atherosclerosis.
This study sought to determine whether calcitonin gene-related peptide (CGRP) is involved in glyceryl trinitrate (GTN) response in humans, and its association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism.
In animal models, CGRP contributes to the cardiovascular effects of GTN. The enzyme principally responsible for GTN bioactivation is ALDH2. The common ALDH2*2 polymorphism is associated with a lack of GTN efficacy.
In 18 ALDH2*2-genotyped Chinese volunteers, we observed the changes in plasma concentrations of CGRP after sublingual GTN administration and its correlation with GTN response, and assessed the expression of CGRP messenger ribonucleic acid (mRNA) in cultured peripheral blood mononuclear cells (PBMCs) pre-treated with 10–5 mol/l GTN.
In contrast to carriers of the ALDH2*2 allele, ALDH2*1/*1 homozygotes showed a significantly higher extent of absolute changes in both systolic blood pressure (SBP) and HR (HR) at several time points after GTN administration. Plasma concentrations of CGRP were increased significantly 12 min after GTN administration, the percentage increase in plasma concentrations of CGRP correlated positively with both SBP and HR, and percentage increase in plasma concentrations of CGRP was significantly higher in ALDH2*1/*1 homozygotes. In addition, PBMCs from ALDH2*1/*1 homozygotes showed a higher-fold increase in both CGRP I and CGRP II mRNA after GTN stimulation, and the GTN-induced increase in CGRP mRNA expression in PBMCs from ALDH2*1/*1 homozygotes was inhibited by the ALDH2 inhibitor chloral hydrate.
We found that CGRP is associated with the cardiovascular effect of GTN through an ALDH2-dependent pathway in humans.