Importance of fatty acid components and imbalances has emerged in coronary heart disease. In this study, we analyzed fatty acids and ankle-brachial index (ABI) in a Japanese cohort.
Peripheral ...arterial disease (PAD) was diagnosed in 101 patients by ABI ≤0.90 and/or by angiography. Traditional cardiovascular risk factors and components of serum fatty acids were examined in all patients (mean age 73.2±0.9 years; 81 males), and compared with those in 373 age- and sex-matched control subjects with no evidence of PAD.
The presence of PAD (mean ABI: 0.71±0.02) was independently associated with low levels of gamma-linolenic acid (GLA) (OR: 0.90; 95% CI: 0.85-0.96; P = 0.002), eicosapentaenoic acid∶arachidonic acid (EPA∶AA) ratio (OR: 0.38; 95% CI: 0.17-0.86; P = 0.021), and estimated glomerular filtration rate (OR: 0.97; 95% CI: 0.96-0.98; P<0.0001), and with a high hemoglobin A1c level (OR: 1.34; 95% CI: 1.06-1.69; P = 0.013). Individuals with lower levels of GLA (≤7.95 µg/mL) and a lower EPA∶AA ratio (≤0.55) had the lowest ABI (0.96±0.02, N = 90), while the highest ABI (1.12±0.01, N = 78) was observed in individuals with higher values of both GLA and EPA∶AA ratio (P<0.0001).
A low level of GLA and a low EPA∶AA ratio are independently associated with the presence of PAD. Specific fatty acid abnormalities and imbalances could lead to new strategies for risk stratification and prevention in PAD patients.
Background : Studies using cardiovascular magnetic resonance imaging have demonstrated subendocardial deposition of amyloid protein in patients with cardiac amyloidosis (CA). We examined whether ...subendocardial dysfunction due to amyloid deposition exists in patients with CA. Methods : We examined 98 consecutive patients with CA and 20 control individuals. CA patients were divided into three groups. Group 1 had no evidence of cardiac involvement (n＝32), group 2 had heart involvement but no congestive heart failure (CHF) and/or serum brain natriuretic peptide (BNP) levels < 100 pg/mL (n＝23), and group 3 had heart involvement and CHF and/or serum BNP levels ≥ 100 pg/mL (n＝43). Circumferential, radial, and longitudinal strains of the inner half and outer half layers of the left ventricular (LV) wall were examined. Results : There was no significant difference in strain parameters between those with AL and ATTRm amyloidosis. There were no significant differences in circumferential inner/outer strain among the 4 groups. Regarding radial strain, groups 2 and 3 had a depressed inner radial strain compared with group 1 in the entire basal and mid-LV wall (P < 0.001, one-way analysis of variance) and that in group 1 was smaller than that in controls. Longitudinal strains of the inner/outer layers in the basal and mid-LV wall were significantly depressed with apical sparing in groups 2 and 3 compared with those in group 1. Conclusions : In patients with CA, complete endomyocardial radial systolic dysfunction and longitudinal transmural systolic dysfunction exist in the basal and mid-LV wall.
Atherosclerosis is a major cause of coronary heart disease, and matrix metalloproteinases (MMPs) play an important role in atherosclerosis by degrading the extracellular matrix, which results in ...cardiovascular remodeling. Recent studies have identified enhanced expression of MMPs in the atherosclerotic lesion and their contribution to weakening of the vascular wall by degrading the extracellular matrix. The transcription, enzyme processing, and specific inhibition of MMPs by tissue inhibitors of matrix metalloproteinase (TIMPs) regulate these effects. These processes are also modified by inflammatory cytokines and cell-cell contact signaling. Both animal experiments and clinical sample analysis have shown that balance in expression and activation of MMPs and inhibition by TIMPs is critical for the development of stenotic and aneurysmal change. Polymorphism in the MMP gene promoter contributes to inter-individual differences in susceptibility to coronary heart disease. The development of therapeutic drugs specifically targeting MMPs may thus be useful for the prevention of atherosclerotic lesion progression, plaque rupture, and restenosis.
Inflammatory cytokines such as interleukin (IL)-1 beta and IL-18 play an important role in the development of atherosclerosis and restenosis. Apoptosis-associated speck-like protein containing a ...caspase recruitment domain (ASC) is an adaptor protein that regulates caspase-1-dependent IL-1 beta and IL-18 generation; however, the role of ASC in vascular injury remains undefined. Here, we investigated the contribution of ASC to neointimal formation after vascular injury in ASC-deficient (ASC(-/-)) mice.
Wire-mediated vascular injury was produced in the femoral artery of ASC(-/-) and wild-type mice. Immunohistochemical analysis revealed that ASC was markedly expressed at the site of vascular injury. Neointimal formation was significantly attenuated in ASC(-/-) mice after injury. IL-1 beta and IL-18 were expressed in the neointimal lesion in wild-type mice but showed decreased expression in the lesion of ASC(-/-) mice. To investigate the contribution of bone marrow-derived cells, we developed bone marrow-transplanted mice and found that neointimal formation was significantly decreased in wild-type mice in which bone marrow was replaced with ASC(-/-) bone marrow cells. Furthermore, in vitro experiments showed that the proliferation activity of ASC(-/-) vascular smooth muscle cells was not impaired.
These findings suggest that bone marrow-derived ASC is critical for neointimal formation after vascular injury and identify ASC as a novel therapeutic target for atherosclerosis and restenosis.
The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary ...intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan–Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank
p
= 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116–0.824;
p
= 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission.
Since the advent of the pneumococcal vaccine, cases of infective endocarditis (IE) from Streptococcus pneumoniae have become rare. Pneumococcal endocarditis (PE) may be the initial presentation in ...Austrian syndrome, which is very lethal. PE needs early detection and treatment and more commonly develops from pneumonia. To our knowledge, this is the first report of PE caused by sinusitis after pneumococcal vaccination. Here, a 71-year-old male presented with low back pain and right ankle joint pain. He had no dental history or pneumonia and received a pneumococcal vaccine 2 years prior. Blood tests showed high inflammatory response. We suspected IE due to the high inflammatory response and oligoarthritis. Transthoracic echocardiography showed vegetation at the aortic valve. As IE was probable, empiric antibiotic therapy was promptly initiated. Blood cultures detected S. pneumoniae. IE was diagnosed based on Duke's diagnostic criteria. After starting antibiotic treatment, lumbar magnetic resonance imaging (MRI) showed an abscess in the right erector spinae. Cranial MRI showed bilateral maxillary sinusitis. Sinusitis was considered the possible initial focus of infection. IE should be considered a differential in patients with S. pneumoniae detected in blood cultures without pneumonia even after pneumococcal vaccination as PE sometimes follows a fatal course.
<Learning objective: Pneumococcal endocarditis (PE) is rare and can be fatal when there is diagnostic delay. It may be less likely to exhibit characteristic skin lesions of infective endocarditis (IE). Clinicians should include IE in the differential diagnoses for cases of Streptococcus pneumoniae detected in blood cultures without pneumonia. Transthoracic echocardiography is also useful for early detection and treatment of PE.>
The Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score is effective in predicting clinical outcome after percutaneous coronary intervention (PCI). However, its prediction ability is ...low because it reflects only the coronary characterization. We assessed the predictive value of combining the ankle-brachial index (ABI) and SYNTAX score to predict clinical outcomes after PCI. The ABI-SYNTAX score was calculated for 1,197 patients recruited from the Shinshu Prospctive Multi-center Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention (SHINANO) registry, a prospective, observational, multicenter cohort study in Japan. The primary end points were major adverse cardiovascular and cerebrovascular events (MACE; all-cause death, myocardial infarction, and stroke) in the first year after PCI. The ABI-SYNTAX score was calculated by categorizing and summing up the ABI and SYNTAX scores. ABI ≤0.49 was defined as 4, 0.5 to 0.69 as 3, 0.7 to 0.89 as 2, 0.9 to 1.09 as 1, and 1.1 to 1.5 as 0; an SYNTAX score ≤22 was defined as 0, 23 to 32 as 1, and ≥33 as 2. Patients were divided into low (0), moderate (1 to 2), and high (3 to 6) groups. The MACE rate was significantly higher in the high ABI-SYNTAX score group than in the lower 2 groups (low: 4.6% vs moderate: 7.0% vs high: 13.9%, p = 0.002). Multivariate regression analysis found that ABI-SYNTAX score independently predicted MACE (hazards ratio 1.25, 95% confidence interval 1.02 to 1.52, p = 0.029). The respective C-statistic for the ABI-SYNTAX and SYNTAX score for 1-year MACE was 0.60 and 0.55, respectively. In conclusion, combining the ABI and SYNTAX scores improved the prediction of 1-year adverse ischemic events compared with the SYNTAX score alone.
Pulmonary arterial hypertension (PAH) is a fatal disease associated with inflammation and pathological remodeling of the pulmonary artery (PA). Interleukin (IL)-10 is a pleiotropic antiinflammatory ...cytokine with vasculoprotective properties. Here, we report the preventive effects of IL-10 on monocrotaline-induced PAH. Three-week-old Wistar rats were intramuscularly injected with an adeno-associated virus serotype 1 vector expressing IL-10, followed by monocrotaline injection at 7 weeks old. IL-10 transduction significantly improved survival rates of the PAH rats 8 weeks after monocrotaline administration compared with control gene transduction (75% versus 0%, P<0.01). IL-10 also significantly reduced mean PA pressure (22.8+/-1.5 versus 29.7+/-2.8 mm Hg, P<0.05), a weight ratio of right ventricle to left ventricle plus septum (0.35+/-0.04 versus 0.42+/-0.05, P<0.05), and percent medial thickness of the PA (12.9+/-0.3% versus 21.4+/-0.4%, P<0.01) compared with controls. IL-10 significantly reduced macrophage infiltration and vascular cell proliferation in the remodeled PA in vivo. It also significantly decreased the lung levels of transforming growth factor-beta1 and IL-6, which are indicative of PA remodeling. In addition, IL-10 increased the lung level of heme oxygenase-1, which strongly prevents PA remodeling. In vitro analysis revealed that IL-10 significantly inhibited excessive proliferation of cultured human PA smooth muscle cells treated with transforming growth factor-beta1 or the heme oxygenase inhibitor tin protoporphyrin IX. Thus, IL-10 prevented the development of monocrotaline-induced PAH, and these results provide new insights into the molecular mechanisms of human PAH.
Background: Atherosclerosis is believed to be caused by oxidative stress. Endovascular therapy (EVT) is effective for claudication of patients with peripheral artery disease (PAD). However, its ...effect on oxidative stress in PAD patients is unknown. Here, the impact of EVT on oxidative stress in PAD patients is investigated. Methods and Results: Twenty-five PAD patients (Rutherford stage II or III) who underwent EVT were enrolled. The levels of diacron-reactive oxygen metabolite (d-ROM; an oxidative stress marker), ankle-brachial index (ABI), and maximum walking distance at baseline and at 3 months after EVT were measured. As compared with baseline values, the maximum walking distance and ABI improved significantly after EVT (109.9±104.2 vs. 313.7±271.8m, P<0.0001; 0.61±0.15 vs. 0.91±0.13m, P<0.0001, respectively). The improved exercise capacity and arterial flow induced a significant decrease in d-ROM levels (from 472.8±64.8 to 390.2±46.7U.CARR; P<0.0001). The decrease in d-ROM levels after EVT was more prominent in PAD patients with a high baseline d-ROM level. The increased ABI (r=0.524, P=0.0007) and maximum walking distance (r=–0.416, P=0.039) after EVT were significantly correlated with the decreased d-ROM levels. Conclusions: The improved exercise capacity and peripheral blood flow induced by EVT decreases oxidative stress in PAD patients. (Circ J 2014; 78: 1445–1450)
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