Dietary salt intake predicts future development of metabolic syndrome in the general population.

Excessive dietary salt consumption is one of the most important risk factors for hypertension. Metabolic disorders often coexist with hypertension, and excess salt intake has been reported to underlie metabolic disorders, such as insulin resistance. Therefore, we tested the hypothesis that excessive dietary salt causes metabolic syndrome in the general population. In total, 13886 subjects who participated in our medical checkup were enrolled, and salt intake was assessed using a spot urine sample. The characteristics of participants with metabolic syndrome (n = 1630) were examined at baseline, and then participants without metabolic syndrome (n = 12256) were followed up with the endpoint being the development of metabolic syndrome. The average estimated salt intake in our participants was 8.72 ± 1.93 g/day. A significant association between salt intake and metabolic syndrome was obtained from the logistic regression analysis, and salt intake increased as the number of metabolic disorders in an individual increased at baseline (P < 0.001). During the median follow-up period of 52 months, 1669 participants developed metabolic syndrome. Kaplan-Meier analysis demonstrated an increased risk of metabolic syndrome across quartiles of baseline salt intake (log-rank, P < 0.001). In the Cox proportional hazard regression analysis where salt intake was taken as a continuous variable, salt intake at baseline was an independent predictor of developing metabolic syndrome. These results suggest that excessive salt intake is significantly associated with the development of metabolic syndrome in the general population. Salt may play an important role in the development of metabolic disorders and hypertension.

Blood pressure variability and the development of hypertensive organ damage in the general population.

Increasing blood pressure variability (BPV) has been reported to be a strong predictor of cardiovascular events in patients with hypertension. However, the effects of BPV in the general population have not been intensively studied. The present study was designed to investigate a possible relationship between year-to-year BPV and hypertensive target organ damage (TOD) in a relatively low-risk general population. A total of 5489 consecutive patients (mean age 58.6 ± 10.7 years) who visited our hospital for an annual physical checkup for five consecutive years during 2008-2013 were enrolled in this study. The average systolic and diastolic blood pressures and pulse pressure were calculated, as well as standard deviation, coefficient of variation, and average real variability in blood pressures. Cross-sectional analysis was conducted and subjects without TOD at baseline (n = 3115) were followed up (median 1827 days) with the endpoint of TOD, defined as left ventricular hypertrophy on electrocardiogram or declining glomerular filtration rate. At baseline, BPV was closely associated with TOD. During follow-up, left ventricular hypertrophy and declining glomerular filtration rate developed in 189 and 400 subjects, respectively. Although the standard deviation for systolic blood pressure and pulse pressure predicted future development of TOD in a univariate analysis, BPV was not a significant determinant of incident TOD in adjusted Cox hazard models. These results suggest that year-to-year BPV is a marker of the presence of TOD in the general population but does not independently predict future TOD.

Current status and recent changes in blood pressure and dietary salt consumption in Japanese individuals.

Purpose: Treatment of hypertension has recently shown remarkable advances. It is quite important to survey the current general status of blood pressure (BP) and recent changes to verify whether people are benefitting from these advances. The present study aimed to investigate the current status of, and recent changes in, BP, the prevalence and treatment rate of hypertension, the achievement rate of target BP, and salt intake in Japanese individuals. Methods: Recent changes in salt intake as well as BP, the prevalence and treatment rate of hypertension, and the rate of achievement of target BP were investigated in participants in our yearly physical checkup program from 2009 to 2018 (n = 79,789). Individual salt intake was assessed by estimating 24-hour urinary sodium excretion using a spot urine sample. Results: The prevalence of hypertension did not change, but the treatment rate of hypertension (from 64% to 75%) and the achievement rate of the target BP improved during the period (from 35% to 57%). BP decreased, prominently in hypertensive participants under antihypertensive treatment (from 133 ± 14/84 ± 9 to 128 ± 13/76 ± 10 mmHg). Salt intake did not decline noticeably during the 10 years of observation. Conclusions: The prevalence of hypertension did not change, but the treatment rate of hypertension and the achievement rate of the target BP improved during a recent 10-year period. These findings suggest that improved pharmacological management of hypertension resulted in a gradual reduction in BP levels, but lifestyle modification has not yet really taken root in the Japanese general population.

Central blood pressure predicts the development of hypertension in the general population.

Although elevated blood pressure results in arterial stiffening, the converse could also be true. Previous studies have suggested that increased arterial stiffness precedes the development of hypertension. Since central blood pressure is augmented following arterial stiffening, the predictive value of central blood pressure for detecting new-onset hypertension was investigated in the general population. A total of 7840 normotensive subjects (male, 4592; mean age, 51 years) were followed up for a median of 4 years, with the endpoint being the development of hypertension. During the actual follow-up period of 31636 person-years, hypertension developed in 2608 subjects. Kaplan-Meier analysis revealed an increase in the risk of hypertension across the quartiles of baseline central blood pressure (log-rank P < 0.001), with incidence rates of hypertension in the first, second, third, and fourth quartiles of 8.8%, 22.3%, 39.9%, and 63.2%, respectively. Multivariate Cox hazard analysis demonstrated an increased hazard ratio of incident hypertension across the quartiles after adjustment for possible factors. Repeating the multivariate Cox hazard analysis with central blood pressure as a continuous variable also identified central blood pressure at baseline as a significant predictor of new-onset hypertension (P < 0.001). These results suggest that central blood pressure is a significant predictor of new-onset hypertension in individuals without hypertension.

Colchicine therapy for deep vein thrombosis in a patient with vascular-type Behçet disease: A case report.

RATIONALE: Behçet Disease (BD) is a chronic inflammatory vasculitis with thrombogenicity and multisystem involvement. Deep vein thrombosis (DVT) in the lower extremities is the most frequent manifestation of vascular involvement in BD. The causes of thrombosis vary widely and include congenital predisposition and acquired factors, but of all the thrombosis, the cause is rarely BD. Furthermore, there are few reports of treatment for thrombosis in BD. PATIENT CONCERNS: We herein describe the case of an Asian male patient aged 40 years, admitted to our hospital for left leg pain, edema, and swelling. DIAGNOSES: We confirmed the DVT and pulmonary artery thrombosis (PAT) by contrast computed tomography angiogram. At the same time, the patient developed oral ulcerations and skin lesions consistent with BD. INTERVENTIONS: The patient was initially treated with anticoagulants. However, because the improvement of DVT was inadequate, we added colchicine in anticipation of anti-inflammatory effects. After that, anticoagulation was discontinued, and only colchicine was continuously prescribed. OUTCOMES: We observed an almost complete resolution of DVT and PAT with no recurrence of thrombosis for 6 months after discharge. LESSONS: This case shows us that we should consider BD as a differential diagnosis of DVT and that colchicine therapy is effective for inflammation-induced thrombosis in BD.

Influence of thyroid dysfunction on brain natriuretic peptide level in health examination participants.

The tissue-specific circulating markers of thyroid hormone action on cardiac function have not been established. Although the relationship between thyroid function and plasma brain natriuretic peptide (BNP) levels has been evaluated in patients with thyroid disorders, the relationship between these parameters in the general population has not been yet studied. We conducted retrospective cohort study by health examination with concurrent measurements of TSH, free T4, body mass index, systolic blood pressure, hemoglobin, and estimated glomerular filtration rate from participants who visited the Department of Health Checkup, Enshu Hospital between July 2008 and March 2017. After participants with abnormal electrocardiogram and/or any history of cardiac disease were excluded, 2,807 individuals were subjected. Multivariate analyses demonstrated that, when compared to euthyroidism (n = 2,629), the increase in BNP levels was significant in overt thyrotoxicosis (n = 21) but not in subclinical thyrotoxicosis (n = 53) or subclinical hypothyroidism (n = 97). Interestingly, the standardized partial regression coefficient was the smallest for thyroid function category (overt thyrotoxicosis compared to euthyroidisim; ß = 0.048, p = 0.006) among the independent variables including age, body mass index, systolic blood pressure, and hemoglobin. In longitudinal comparison, we identified 986 participants who had sequential data on the measurements and were stable as euthyroidism and subclinical hypothyroidism. Their annual percent change in BNP demonstrated no significant differences. In conclusion, a direct stimulatory effect of thyroid hormone on the secretion (or production) of BNP was confirmed even in a large number of health examination participants.

Intraventricular thrombus and severe mitral regurgitation in the acute phase of takotsubo cardiomyopathy: two case reports.

BACKGROUND: Takotsubo cardiomyopathy is characterized by chest symptoms, electrocardiographic changes, and new regional wall motion abnormality in the apical segment of the left ventricle in the absence of obstructive coronary artery disease. Particularly, apical ballooning is broadly recognized as the classic form of takotsubo cardiomyopathy. Although the prognosis of most patients with takotsubo cardiomyopathy is generally favorable, complications associated with the morphological features of transient apical ballooning are not uncommon. CASE PRESENTATION: We describe two cases of transient complications in postmenopausal patients with takotsubo cardiomyopathy. Intraventricular thrombus was observed in Asian patient 1, and severe mitral regurgitation was observed in Asian patient 2. These complications were confirmed by transthoracic echocardiography immediately after typical takotsubo cardiomyopathy with apical ballooning was diagnosed. Anticoagulant therapy with heparin and warfarin was continued for 1 week in patient 1. After the therapy, complete resolution of the apical thrombus and recovery of systolic function of the left ventricle was observed by follow-up transthoracic echocardiography. In patient 2, transthoracic echocardiography indicated significant mitral regurgitation, which was caused by left ventricular tethering of the anterior mitral leaflet rather than left ventricular outflow tract obstruction or systolic anterior motion. Because the hemodynamic stability in patient 2 had been preserved, she was managed with conservative treatment. After approximately 1 month, follow-up transthoracic echocardiography revealed that mitral regurgitation had almost disappeared with complete resolution of left ventricular wall motion abnormalities. CONCLUSIONS: The presented cases indicated that important complications, such as intraventricular thrombus and severe mitral regurgitation, are associated with takotsubo cardiomyopathy in the acute phase. Because these complications are risk factors for developing a thromboembolic event or heart failure and/or pulmonary edema, timely and accurate identification of these complications is critical to achieving optimal clinical outcomes in patients with takotsubo cardiomyopathy.

Effect of combined therapy with catheter-directed thrombolysis and factor Xa inhibitor for inferior vena cava thrombosis: A case report.

RATIONALE: Inferior vena cava (IVC) thrombosis is an under-recognized entity that is associated with a mortality rate approaching twice that of lower extremity deep venous thrombosis (DVT). Thrombolytic therapy not only results in greater lysis, but also results in higher complication rates than anticoagulation alone. Catheter-directed thrombolysis (CDT), which is effective in accomplishing local resolution whilst reducing bleeding complications, has been established as an alternative treatment for patients with extensive DVT. PATIENT CONCERNS: We report the case of a 70-year-old man who was admitted due to warmness, pain, and swelling in his left leg and a feeling of gait disturbance. DIAGNOSES: Contrast-enhanced computed tomography and venous ultrasonography revealed a pulmonary embolism and extensive DVT spreading to the IVC. INTERVENTIONS: First, the patient was treated with fondaparinux. Since this was inadequate, he underwent CDT using a Fountain infusion catheter. Then, CDT was switched to direct oral anticoagulant (DOAC) treatment. OUTCOMES: Both CDT and subsequent DOAC treatments dramatically improved the DVT. His subjective symptoms have disappeared, and no recurrence of thrombosis has been identified. LESSONS: The present case showed the therapeutic effect of CDT, which preceded DOAC treatment, on an extensive DVT.

Purulent Pericarditis with Salmonella enterica Subspecies arizona in a Patient with Type 2 Diabetes Mellitus.

Purulent pericarditis is a life-threatening disorder, even in the modern antibiotic era. Although diabetes mellitus is known to be associated with an increased risk of multiple types of infections, purulent pericarditis is extremely rare. We herein report an unusual case of pericarditis caused by Salmonella enterica subspecies arizona that was not associated with any evident underlying immunosuppressive disorder apart from uncontrolled type 2 diabetes mellitus. Because a pet snake was suspected as being the source of infection in the present case, patient education and a detailed review of exposure history could play an important role in treating patients with diabetes mellitus.

Recent changes in blood pressure levels, hypertension prevalence and treatment rates, and the rate of reaching target blood pressure in the elderly.

Antihypertensive treatment has beneficial effects in the elderly. Surveying the situation of blood pressure in the elderly is quite important for planning strategies to manage elderly hypertensives. The aim of the present study was to investigate changes in blood pressure in the elderly over the past 15 years.As part of a physical check-up program between 2001 and 2015, 29,363 elderly participants (≥65 years of age) attended and were enrolled in the present study. The characteristics of the participants in each year were analyzed cross-sectionally and the results were compared over the 15 years. Changes in blood pressure, hypertension prevalence, and treatment rates, and the rate of reaching target blood pressure in the elderly were investigated.The prevalence of hypertension during the study period increased with increasing participant age. However, both the treatment rate and the rate of reaching target blood pressure in treated subjects improved. The blood pressure of treated hypertensive elderly subjects decreased from 146.1/83.0 to 130.6/75.4 mm Hg, and the reduction was most evident after revision of Japanese Society of Hypertension guidelines regarding target blood pressure in elderly hypertensives. Blood pressure in the entire cohort of elderly subjects decreased from 133.8/78.4 mm Hg in 2001 to 127.9/74.6 mm Hg in 2015.Blood pressure in elderly subjects had decreased over the 15-year study period primarily due to reductions in blood pressure in elderly hypertensive patients on medication. Guidelines for the treatment of hypertension have had a beneficial effect on the management of hypertension in the elderly.

Distribution of late gadolinium enhancement in end-stage hypertrophic cardiomyopathy and dilated cardiomyopathy: differential diagnosis and prediction of cardiac outcome.

BACKGROUND: The prognostic implications of late gadolinium enhancement (LGE) have been evaluated in ischemic and non-ischemic cardiomyopathies. The present study analyzed LGE distribution in patients with end-stage hypertrophic cardiomyopathy (ES-HCM) and with dilated cardiomyopathy (DCM), and tried to identify high risk patients in DCM. METHODS: Eleven patients with ES-HCM and 72 with DCM underwent cine- and LGE-cardiac magnetic resonance and ultrasound cardiography. The patient outcome was analyzed retrospectively for 5years of follow-up. RESULTS: LGE distributed mainly in the inter-ventricular septum, but spread more diffusely into other left ventricular segments in patients with ES-HCM and in a certain part of patients with DCM. Thus, patients with DCM can be divided into three groups according to LGE distribution; no LGE (n=24), localized LGE (localized at septum, n=36), and extensive LGE (spread into other segments, n=12). Reverse remodeling occurred after treatment in patients with no LGE and with localized LGE, but did not in patients with extensive LGE and with ES-HCM. The event-free survival rate for composite outcome (cardiac death, hospitalization for decompensated heart failure or ventricular arrhythmias) was lowest in patients with extensive LGE (92%, 74% and 42% in no LGE, localized LGE, and extensive LGE, p=0.02 vs. no LGE), and was comparable to that in patients with ES-HCM (42%). CONCLUSIONS: In DCM, patients with extensive LGE showed no functional recovery and the lowest event-free survival rate that were comparable to patients with ES-HCM. The analysis of LGE distribution may be valuable to predict reverse remodeling and to identify high-risk patients.

Ultrasound analysis of the relationship between right internal jugular vein and common carotid artery in the left head-rotation and head-flexion position.

Common carotid artery (CCA) injury is a serious complication of internal jugular vein (IJV) cannulation. To minimize unintentional CCA puncture, the anatomic relationship between the IJV and the CCA and the size of IJV were compared under different head positions. Ultrasound analyses of the IJV and the CCA were performed in 103 consecutive patients. Overlapping angle (OA), real puncture angle (RPA) and diameter of IJV (D IJV) were evaluated with 30° and 60° left rotation and with 30° left flexion. When the head position was changed from 30° left rotation to 60° left rotation, OA increased significantly from 6.5° ± 7.7° to 14.5° ± 7.4° at the cricoid cartilage level (Cricoid-level) and from 14.4° ± 8.4° to 20.6° ± 6.9° at the middle triangle level (Triangle-level), whereas RPA decreased significantly at these levels (from 49.7° ± 11.9° to 43.5° ± 13.1° and from 51.1° ± 14.4° to 44.3° ± 13.9°, respectively; P < 0.01 for both). When the head position was changed from 30° left rotation to 30° left flexion, neither OA nor RPA significantly changed (OA: 6.3° ± 6.1° and 15.0° ± 7.2°, RPA: 48.5° ± 12.4° and 51.8° ± 13.6°, P not significant vs 30° left rotation). There was no difference in D IJV when comparing 30° left rotation and 30° left flexion, although D IJV was largest at 60° left rotation. RPA positively correlated with age, and D IJV positively correlated with body mass index. In conclusion, excessive left rotation should be avoided to minimize the probability of unintentional CCA puncture during IJV cannulation. When 30° left rotation is not feasible, the head-flexion position should be utilized.

Irxl1 mutant mice show reduced tendon differentiation and no patterning defects in musculoskeletal system development.

Irxl1 (Iroquois-related homeobox like-1) is a newly identified three amino-acid loop extension (TALE) homeobox gene, which is expressed in various mesoderm-derived tissues, particularly in the progenitors of the musculoskeletal system. To analyze the roles of Irxl1 during embryonic development, we generated mice carrying a null allele of Irxl1. Mice homozygous for the targeted allele were viable, fertile, and showed reduced tendon differentiation. Skeletal morphology and skeletal muscle weight in Irxl1-knockout mice appeared normal. Expression patterns of several marker genes for cartilage, tendon, and muscle progenitors in homozygous mutant embryos were unchanged. These results suggest that Irxl1 is required for the tendon differentiation but dispensable for the patterning of the musculoskeletal system in development.

Intravenous glutathione prevents renal oxidative stress after coronary angiography more effectively than oral N-acetylcysteine.

This study proposes the intravenous administration of glutathione (GSH) as a novel strategy to prevent contrast medium-induced renal oxidative stress. Renal oxidative stress is a critical cause of contrast-induced nephropathy (CIN). Recent reports have described that N-acetylcysteine (NAC) may prevent CIN by scavenging reactive oxygen species in the kidney. Twenty-one patients with reduced renal function who underwent coronary angiography (CAG) were equally assigned to the control, NAC and GSH (100 mg/min for 30 min before CAG) groups. CIN occurred in two patients, one in the control and the other in the NAC group. In the control group, the urinary lipid hydroperoxides (LOOHs) increased to 299.5 ± 94.4% of the baseline at 2 h after CAG (mean ± SE, p < 0.01). The increase in LOOHs was completely abolished in the GSH group (5.5 ± 8.8%, p = ns), but not in the NAC group (196.8 ± 81.3%, p < 0.05). In the control group, the serum GSH level fell by 9.4 ± 2.3% at 2 h after CAG (p < 0.01). The decrease was prevented in the GSH group (-1.8 ± 8.5%, p = ns), but not in the NAC group (-10.0 ± 3.3%, p < 0.05). The renal damage by contrast medium-induced oxidative stress occurs soon after CAG, and intravenous GSH is more effective in preventing the oxidative stress than oral NAC. This advantage may make GSH a potentially more effective therapeutic strategy against CIN.

Vasodilator stress impairs the left ventricular function obtained with gated single-photon emission computed tomography in patients with known or suspected coronary artery disease.

BACKGROUND: Transient ischemic dilatation (TID) and post-stress dysfunction of the left ventricle (LV) are important markers of severe coronary artery disease (CAD). To clarify the effects of stressor type on TID and post-stress LV dysfunction, changes in LV measurements were compared between patients with exercise- or vasodilator-induced stress. METHODS AND RESULTS: The 689 patients referred for technetium-99m tetrofosmin myocardial perfusion imaging were included. Patients were stressed with either a vasodilator (n=236) or exercise (n=453). LV measurements were obtained with ECG-gated SPECT. LV end-diastolic and end-systolic volume indexes (LVEDVI, LVESVI) increased and LV ejection fraction (LVEF) decreased after stress in the vasodilator-stress group. Vasodilator-stress and the summed difference score (SDS) were independent variables that decreased LVEF after stress. Even in patients without reversible defects, vasodilator-stress impaired LV function. There were no differences in the stress-to-rest ratios of LVEDVI (rEDV) and LVESVI (rESV) among patients with normal myocardial perfusion, fixed defects and reversible defects in the vasodilator-stress group, whereas in the exercise-stress group, rESV was significantly higher in the patients with reversible defects than in those without reversible defects. Within the vasodilator-stress group, neither rEDV nor rESV correlated with the SDS. CONCLUSIONS: Vasodilator-stress by itself decreases LVEF after stress. TID should be carefully interpreted when vasodilator-stress is used to detect severe CAD.