Assessment of visit-to-visit variability in systolic blood pressure over 5 years and phasic left atrial function by two-dimensional speckle-tracking echocardiography.

Visit-to-visit variability in systolic blood pressure (VVV-SBP) has been associated with increased cardiac events. Hence, volume analysis by two-dimensional speckle-tracking echocardiography (2-DSTE) allows physicians to easily measure phasic left atrial (LA) function. However, the relationship of VVV-SBP and functional deformation of the left atrium with patients' clinical outcome is unclear. The aim of the study was to investigate the relationship between phasic LA function and VVV-SBP. The subjects were 70 male participants in whom 2-DSTE was performed to measure blood pressure at health check-ups every year for 5 years. The standard deviation of systolic blood pressure (SBP) was calculated to assess VVV-SBP. The average SBP (Ave-SBP) was also assessed. Total emptying function (EF) (reservoir function), passive EF (conduit function), and active EF (booster pump function) of the left atrium were calculated to evaluate phasic LA function by 2-DSTE. The Pearson correlation, simple regression analysis, and multivariate logistic regression analysis were used in data analysis. Participants' mean age was 50 ± 10 years, and 16 participants had hypertension. VVV-SBP correlated with total EF (r = - 0.30, p = 0.014) and active EF (r = - 0.35, p = 0.003). There was no correlation between the standard deviation of SBP and passive EF (r = - 0.10, p = 0.39). Ave-SBP had no significant relationship with total EF (r = - 0.06, p = 0.62), passive EF (r = - 0.08, p = 0.50), or active EF (r = - 0.03, p = 0.78). Active EF was also associated with VVV-SBP in multiple regression analysis. The active EF was significantly decreased in the highest quartile of VVV-SBP. Despite the small sample size of our study, the VVV-SBP showed a relationship with the phasic LA function. Our findings suggest that high VVV-SBP is noted to be associated with cardiovascular risk including a deterioration of LA function in clinical practice.

Left Ventricular Torsion in Hypertension and Hypertensive Heart Failure　- 3-Dimensional Speckle Tracking Echocardiography Assessment.

Background: Left ventricular (LV) torsion by contraction of inner and outer oblique muscles contributes to EF. Outer muscle plays a predominant role in torsion. We evaluated the impact of LV remodeling by hypertension (HTN) on torsion using 3-dimensional speckle tracking echocardiography (3D-STE). Methods and Results: LV strain, strain rate during systole (SR-S) and torsion at endocardium, mid-wall and epicardium were assessed on 3D-STE in 53 controls and 186 HTN patients. Torsion was defined as the difference between apical and basal rotation divided by long axis length. LVEF and strain, SR-S and torsion in all 3 layers in HTN without LV hypertrophy (LVH) were similar to those in controls. LV longitudinal strain at endocardium in HTN with LVH decreased, whereas LVEF was similar to that in controls and, which was associated with increased torsion at epicardium. Reduced LVEF in hypertensive HF was associated with reduced strain, SR-S and torsion in all layers and with LV dilation. On multivariate analysis, epicardial torsion was an independent determinant of LVEF. At epicardial torsion cut-off 0.41, the sensitivity and specificity for the identification of HFrEF were 88% and 68%. Conclusions: Torsion on 3D-STE may represent a compensatory mechanism to maintain LVEF despite reduced endocardial function, suggesting that the deterioration of torsion caused by insult to outer muscle and dilation may lead to HFrEF.

Non-Invasive Pulmonary Capillary Wedge Pressure Assessment on Speckle Tracking Echocardiography as a Predictor of New-Onset Non-Valvular Atrial Fibrillation　- Four-Year Prospective Study (NIPAF Study).

BACKGROUND: Although new-onset atrial fibrillation (AF) increases with ageing, the prediction of new-onset AF is complicated. We previously reported that pulmonary capillary wedge pressure (ePCWP) estimated by the combination of left atrial volume index (LAVI) and active left atrial emptying function (aLAEF) had a strong relationship with PCWP on catheterization (r=0.92): ePCWP=10.8-12.4×log (aLAEF/minimum LAVI). We sought to determine the usefulness of ePCWP to predict new-onset AF. Methods and Results: We measured LAVI, aLAEF and ePCWP on speckle tracking echocardiography (STE) in 566 consecutive elderly patients (72±6 years) without a history of AF. A total of 63 patients (73±6 years) developed electrocardiographically confirmed AF during a mean follow-up period of 50 months. Baseline aLAEF was significantly lower in patients with than without new-onset AF (17.9±6.5 vs. 28.2±7.5%), whereas ePCWP was significantly higher (14.8±3.7 vs. 10.3±3.1 mmHg). In multivariate logistic regression analysis, ePCWP and aLAEF were strong independent predictors of AF. Using ePCWP >13 mmHg or aLAEF ≤22% on univariate Cox regression analysis, the HR for new-onset AF were 3.53 (95% CI: 1.68-7.44, P<0.001) and 4.06 (95% CI: 1.90-8.65, P<0.001), respectively. By combining these 2 criteria (>13 mmHg and ≤22%), the HR increased to 11.84 (95% CI: 6.85-20.5, P<0.001). CONCLUSIONS: ePCWP and aLAEF measured on STE are useful predictors of new-onset AF. ePCWP provides added value for risk stratification of new-onset AF.

Impact of tissue characteristics on luminal narrowing of mild angiographic coronary stenosis: assessment of integrated backscatter intravascular ultrasound.

Integrated backscatter intravascular ultrasound (IB-IVUS) is a useful method for analyzing coronary plaque tissue. We evaluated whether tissue composition determined using IB-IVUS is associated with the progression of stenosis in coronary angiography. Sixty-three nontarget coronary lesions in 63 patients with stable angina were evaluated using conventional IVUS and IB-IVUS. IB-IVUS images were analyzed at 1-mm intervals for a length of 10 mm. After calculating the relative areas of the tissue components using the IB-IVUS system, fibrous volume (FV) and lipid volume (LV) were calculated through integration of the slices, after which percentages of per-plaque volume (%FV/PV, %LV/PV) and per-vessel volume (%FV/VV, %LV/VV) were calculated. Progression of coronary stenosis was interpreted from the increase in percent diameter stenosis (%DS) from baseline to the follow-up period (6-9 months) using quantitative coronary angiography. %DS was 24.1 ± 12.8 % at baseline and 23.2 ± 13.7 % at follow-up. Using IB-IVUS, LV was 31.7 ± 10.5 mm(3), and %LV/PV and %LV/VV were 45.6 ± 10.3 % and 20.2 ± 6.0 %, respectively. FV, %FV/PV, and %FV/VV were 35.5 ± 12.1 mm(3), 52.1 ± 9.5 %, and 23.4 ± 7.1 %, respectively. The change in %DS was -0.88 ± 7.25 % and correlated closely with %LV/VV (r = 0.27, P = 0.03) on simple regression. Multivariate regression after adjustment for potentially confounding risk factors showed %LV/VV to be correlated independently with changes in %DS (r = 0.42, P = 0.02). Logistic regression analysis after adjusting for confounding coronary risk factors showed LV (odds ratio 1.08; 95 % confidence interval 1.01-1.16; P = 0.03) and %LV/VV (odds ratio 1.13; 95 % confidence interval 1.01-1.28; P = 0.03) to be independent predictors of the progression of angiographic coronary stenosis. Our findings suggest that angiographic luminal narrowing of the coronary artery is likely associated with tissue characteristics. IB-IVUS may provide information about the natural progression of luminal narrowing in coronary stenosis.

Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals.

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease. Although genetic studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. The purpose of the present study was to identify genetic variants that confer susceptibility to hypertension in Japanese individuals. METHODS: A total of 5,734 Japanese individuals from two independent populations were examined: subject panel A comprised 2,066 hypertensive individuals and 824 controls; and subject panel B comprised 834 hypertensive individuals and 2,010 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of myocardial infarction and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). RESULTS: The chi(2)-test revealed that 10 polymorphisms were significantly (P < 0.05) related to the prevalence of hypertension in subject panel A. To validate the relations, these polymorphisms were examined in subject panel B. The A-->G polymorphism (rs645106) of SDK1 and the C-->G polymorphism (rs12078839) of RABGAP1L were significantly associated with hypertension in subject panel B. Multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the A-->G polymorphism of SDK1 was significantly associated with hypertension in both subject panels A and B, with the G allele protecting against this condition. CONCLUSIONS: SDK1 may be a susceptibility gene for hypertension in Japanese individuals, although the functional relevance of the identified polymorphism was not determined.

Assessment of genetic risk factors for thoracic aortic aneurysm in hypertensive patients.

BACKGROUND: Conventional risk factors for thoracic aortic aneurysm including dissection (TAA) are thought to include age, arteriosclerosis, and hypertension. In addition, evidence suggests that genetic factors play a role in the development of this condition. The purpose of the present study was to identify genetic variants that confer susceptibility to TAA in hypertensive subjects. METHODS: Study subjects comprised 1,351 hypertensive individuals: 88 patients with TAA and 1,263 subjects without this condition. The genotypes for 142 polymorphisms of 119 candidate genes were determined by a method that combines the PCR and sequence-specific oligonucleotide probes with suspension array technology. RESULTS: Evaluation of genotype distributions by the chi2-test and subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the 3949T-->G (3' untranslated region) polymorphism of the thrombospondin-2 gene (THBS2; odds ratio, 4.6), the -110A-->C polymorphism of the heat shock 70-kDa protein 8 gene (HSPA8; odds ratio, 0.4), the C-->T (Pro198Leu) polymorphism of the glutathione peroxidase 1 gene (GPX1; odds ratio, 0.3), the -6G-->A polymorphism of the angiotensinogen gene (AGT; odds ratio, 0.3), and the -850C-->T polymorphism of the tumor necrosis factor gene (TNF; odds ratio, 0.5) were significantly (P < 0.05) associated with TAA. CONCLUSIONS: The variant allele of THBS2 is a risk factor for TAA in hypertensive patients, whereas the variant alleles of HSPA8, GPX1, AGT, and TNF are protective against this condition. Determination of genotypes for these polymorphisms may prove informative for assessment of the genetic risk for TAA.

Assessment of the genetic component of hypertension.

BACKGROUND: Although genetic epidemiologic studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. We have now performed a large-scale association study to identify gene polymorphisms for reliable assessment of the genetic component of hypertension. METHODS: The study population comprised 4853 unrelated Japanese individuals, including 2818 subjects with hypertension (1677 men, 1141 women) and 2035 controls (1011 men, 1024 women). The genotypes for 150 polymorphisms of 128 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. RESULTS: Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking revealed that four polymorphisms (1648G-->A in ITGA2, -30G-->A in GCK, A-->G in SAH, and 1117C-->A in PTGIS) were significantly (P < .01) associated with hypertension. A stepwise forward selection procedure demonstrated that ITGA2, GCK, and PTGIS genotypes significantly affected the prevalence of hypertension. Combined genotype analysis of these polymorphisms yielded a lowest odds ratio of 0.47 for the genotypes of AA or AG for ITGA2, GA or AA for GCK, and CC for PTGIS, which were present in 1.1% and 2.0% of hypertensive and control individuals, respectively. CONCLUSIONS: These results suggest that the genotypes for ITGA2, GCK, and PTGIS may prove reliable for the assessment of the genetic component of hypertension. Determination of the combined genotypes for these genes may contribute to personalized prevention of this condition.

Assessment of genetic risk for myocardial infarction.

Although lifestyle and environmental factors influence the prevalence of myocardial infarction, genetic epidemiological studies have suggested that several genetic variants increase the risk for this condition. We have performed a large-scale association study to identify gene polymorphisms for reliable assessment of the genetic risk of myocardial infarction. The study population comprised 3,483 unrelated Japanese individuals (1,913 men; 1,570 women), including 1,192 subjects with myocardial infarction and 2,291 controls. The genotypes for 164 polymorphisms of 137 candidate genes were determined with an oligonucleotide ligation assay based on analysis of fluorescent microspheres with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hypercholesterolemia revealed that the 677C-->T (Ala222Val) polymorphism of MTHFR, the 1595C-->G (Ser447Stop) polymorphism of LPL, and the -108/3G-->4G polymorphism of IPF1 were significantly associated with the prevalence of myocardial infarction. A stepwise forward selection procedure demonstrated that IPF1, MTHFR, and LPL genotypes significantly affected the prevalence of myocardial infarction. Combined genotype analysis of these polymorphisms yielded a maximum odds ratio of 2.54 for the combined genotype of TT for MTHFR, CC for LPL, and 3G3G for IPF1. The genotypes for MTHFR, LPL, and IPF1 may prove reliable for assessment of genetic risk for myocardial infarction. Determination of the combined genotype for these genes may contribute to primary, personalized prevention of this condition.

Assessment of genetic factors for type 2 diabetes mellitus.

The purpose of the present study was to identify gene polymorphisms for reliable assessment of genetic factors for type 2 diabetes mellitus. The study population comprised 4853 unrelated Japanese individuals (2688 men, 2165 women), including 1489 subjects with type 2 diabetes mellitus (969 men, 520 women) and 3364 controls (1719 men, 1645 women). The genotypes for 148 polymorphisms of 124 candidate genes were determined with a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Sixteen polymorphisms were related (p<0.05) to the prevalence of type 2 diabetes mellitus as determined by the chi-square test. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of smoking revealed that, among these polymorphisms, the -603A --> G polymorphism of the gene for coagulation factor III (F3) was significantly (p<0.001) associated with the prevalence of type 2 diabetes mellitus, with the -603G allele representing a risk factor for this condition. A stepwise forward selection procedure demonstrated that F3 genotype (GG versus AA + AG) significantly (p<0.001) and independently affected the prevalence of type 2 diabetes mellitus. Genotype for F3 may prove reliable for assessment of genetic factors for type 2 diabetes mellitus. Determination of the genotype for this gene may contribute to personalized prevention of this condition.

Myocardial perfusion during transient slow-flow in the patient with old vein graft intervention: assessment by serial measurement of pressure-derived fractional flow reserve and thermodilution-derived coronary flow reserve.

A patient with distal slow-flow after stenting in the old vein graft intervention was reported. This case is a first in whom guidewire-based serial measurement of pressure-derived fractional flow reserve (FFR(myo)) and thermodilution-based coronary flow reserve (CFR(thermo)) clearly demonstrated the serial change of microvascular circulation. During slow-flow, CFR(thermo) remained in low value despite significant improvement of FFR(myo) from 0.61 to 0.90. After thrombus aspiration and nicorandil injection, coronary flow reestablished immediately. CFR(thermo) improved significantly from 1.3 during slow-flow to 3.6 after restoration of flow.