Deterioration of Phosphate Homeostasis Is a Trigger for Cardiac Afterload - Clinical Importance of Fibroblast Growth Factor 23 for Accelerated Aging.

After the discovery of the Klotho gene, phosphate came into focus as a pathogenetic aging agent. Phosphate homeostasis is controlled by phosphate-regulating hormones: fibroblast growth factor 23 (FGF23), vitamin D, and parathyroid hormone. This study investigated the relationship between the deterioration in phosphate homeostasis and arterial stiffness by measuring serum FGF23 concentrations.

β-Blockers are associated with increased B-type natriuretic peptide levels differently in men and women in heart failure with preserved ejection fraction.

β-Blocker (BB) use is a mainstay for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF), whereas its efficacy for heart failure with preserved ejection fraction (HFpEF) remains controversial. Women outnumber men in HFpEF, whereas men outnumber women in HFrEF. Plasma B-type natriuretic peptide (BNP) is established as a biomarker for HF.

Incidence, clinical characteristics, and diagnostic approach in transthyretin amyloid cardiomyopathy: The Kumamoto Cardiac Amyloidosis Survey.

Background: In recent years, transthyretin amyloid cardiomyopathy (ATTR-CM) has received increasing attention; however, the epidemiology of ATTR-CM in Japan is not yet understood. In the Kumamoto Cardiac Amyloid Survey, we evaluated the current incidence, clinical characteristics, diagnostic approaches, and treatment strategies for ATTR-CM and compared tafamidis-prescription hospitals with regional hospitals.

Methods: We conducted a retrospective multicenter observational cohort study.

East Asian variant aldehyde dehydrogenase type 2 genotype exacerbates ischemia/reperfusion injury with ST-elevation myocardial infarction in men: possible sex differences.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes generated during ischemia/reperfusion (I/R) injury in ST-elevation myocardial infarction (STEMI). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. Whether ALDH2*2 exacerbates I/R injury of in patients with STEMI is not known.

East Asians Variant Mitochondrial Aldehyde Dehydrogenase 2 Genotype Exacerbates Nitrate Tolerance in Patients With Coronary Spastic Angina.

Background: Aldehyde dehydrogenase 2 (ALDH2) plays a central role in the biotransformation of glyceryl trinitrate (GTN) or nitroglycerin, which is widely used for the treatment of coronary artery disease (CAD). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. This study examined whether there are differences in nitroglycerine-mediated dilation (NMD) and flow-mediated dilation (FMD) response between wildALDH2*1/*1and variantALDH2*2patients with CAD.

Association of East Asian Variant Aldehyde Dehydrogenase 2 Genotype (ALDH2*2*) with Coronary Spasm and Acute Myocardial Infarction.

Coronary spasm plays an important role in the pathogenesis of ischemic heart disease, including angina pectoris, acute myocardial infarction (AMI), silent myocardial ischemia, and sudden death. The prevalence of coronary spasm is higher among East Asians probably due to genetic as well as environmental factors. ALDH2 eliminates toxic aldehydes including 4-hydroxy-2-nonenal (4-HNE) derived from lipid peroxidation and acrolein in tobacco smoking as well as ethanol-derived acetaldehyde and thereby protects tissues and cells from oxidative damage.

Coronary artery spasm - Clinical features, pathogenesis and treatment.

Coronary artery spasm (CAS) plays an important role in the pathogenesis of ischemic heart disease, including angina pectoris, myocardial infarction, and sudden death, occurring most often from midnight to early morning. CAS is prevalent among East Asians and is associated with an aldehyde dehydrogenase 2 (ALDH2)-deficient genotype (ALDH2*2) and alcohol flushing, which is prevalent among East Asians but is virtually non-existent in other populations. ALDH2 eliminates not only acetaldehyde but also other toxic aldehydes from lipid peroxidation and tobacco smoking, thereby protecting tissues and cells from oxidative damage.

Sex Differences in Heart Failure With Preserved Ejection Fraction Reflected by B-type Natriuretic Peptide Level.

Background: Prevalence of heart failure with preserved ejection fraction (HFpEF) increases with advancing age, particularly among women. Plasma levels of B-type natriuretic peptide (BNP), a surrogate marker of heart failure, have consistently been shown to be higher in women in the general populations. Whether BNP levels differ as per the sex of HFpEF patients remains largely unknown.

The diabetic heart utilizes ketone bodies as an energy source.

Background: Diabetic heart is characterized by failure of insulin to increase glucose uptake and increasingly relies on free fatty acids (FFAs) as a source of fuel in animal models. However, it is not well known how cardiac energy metabolism is altered in diabetic hearts in humans. We examined cardiac fuel metabolism in the diabetics as compared to non-diabetics who underwent cardiac catheterization for heart diseases.

B-Type Natriuretic Peptide in Heart Failure With Preserved Ejection Fraction - Relevance to Age-Related Left Ventricular Modeling in Japanese.

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is increasing with aging of the population. Plasma levels of B-type natriuretic peptide (BNP) increase in proportion to the severity of left ventricular (LV) dysfunction. The object of this study was to examine the plasma levels of BNP in HFpEF to better understand the pathogenesis of HFpEF as compared with HF with reduced EF (HFrEF).

Variant Aldehyde Dehydrogenase 2 (ALDH2*2) in East Asians Interactively Exacerbates Tobacco Smoking Risk for Coronary Spasm - Possible Role of Reactive Aldehydes.

Background: Coronary spastic angina (CSA) is common among East Asians and tobacco smoking (TS) is an established risk factor for CSA. Aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing reactive toxic aldehydes and a deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined the interaction between TS andALDH2*2as a risk factor for CSA to better understand the disease pathogenesis.

Brain Natriuretic Peptide Counteracting the Renin-angiotensin-aldosterone System in Accelerated Malignant Hypertension.

We describe 2 patients, a 52-year-old woman and a 57-year-old man, with rapidly progressive hypertension and marked elevation of brain natriuretic peptide who exhibited polyuria, natriuresis, hypokalemia, posterior reversible encephalopathy syndrome and left ventricular dysfunction together with retinopathy and nephropathy, which were attenuated in a short time span of 1-2 months with normalization of blood pressure after the antihypertensive treatment. The possible role of brain natriuretic peptide in the pathophysiology of accelerated malignant hypertension was discussed and a review of the literature was completed.

Variant Aldehyde Dehydrogenase 2 (ALDH2*2) Is a Risk Factor for Coronary Spasm and ST-Segment Elevation Myocardial Infarction.

Background: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing toxic aldehydes. Deficient variant ALDH2*2 genotype is prevalent in up to 40% of the East Asians and reported to be associated with acute myocardial infarction (AMI). To elucidate the mechanisms underlying the association of ALDH2*2 with AMI, we compared the clinical features of AMI patients with ALDH2*2 to those with wild-type ALDH2*1/*1.

East asian variant of aldehyde dehydrogenase 2 is associated with coronary spastic angina: possible roles of reactive aldehydes and implications of alcohol flushing syndrome.

Background: Coronary spastic angina (CSA) is a common disease among East Asians, including Japanese. The prevalence of alcohol flushing syndrome associated with deficient activity of the variant aldehyde dehydrogenase 2 (ALDH2*2) genotype is prevalent among East Asians. We examined whether CSA is associated with the ALDH2*2 genotype in Japanese.

Pioglitazone, a peroxisome proliferator-activated receptor γ activator, suppresses coronary spasm.

Objective: We examined whether a peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, pioglitazone, suppresses coronary spasm.

Background: Patients with coronary spastic angina (CSA) also have endothelial dysfunction and inflammation. Activation of PPAR-γ improves endothelial dysfunction and inflammation.

Alcohol flushing and positive ethanol patch test in patients with coronary spastic angina: possible role of aldehyde dehydrogenase 2 polymorphisms.

Objective: Coronary spasm plays an important role in the pathogenesis of coronary heart disease (CHD) and angina pectoris caused by coronary spasm or coronary spastic angina (CSA) is prevalent in Japan. However, the precise mechanisms underlying coronary spasm are unclear. Alcohol intolerance is prevalent among East Asians, and we previously reported that coronary spasm could be induced by alcohol intake in CSA patients.

Coronary spastic angina is associated with insulin resistance - possible involvement of endothelial dysfunction.

Objective: In this study, we examined whether coronary spastic angina (CSA) is associated with insulin resistance.

Background: There is increasing evidence that insulin resistance is associated with endothelial dysfunction. Patients with CSA show endothelial dysfunction.

Suppression of primary aldosteronism and resistant hypertension by the peroxisome proliferator-activated receptor gamma agonist pioglitazone.

The peroxisome proliferator-activated receptor gamma (PPAR γ) agonists have been reported to have antiproliferative and tumor-suppressive effects. We report a case of 55-year-old man with primary aldosteronism (PA) whose hyperaldosteronism was suppressed with the PPAR γ agonist pioglitazone. He had drug-resistant hypertension, hypokalemia, and diabetes mellitus.

Aerobic interval exercise training in the afternoon reduces attacks of coronary spastic angina in conjunction with improvement in endothelial function, oxidative stress, and inflammation.

Background: Coronary spasm plays an important role in the pathogenesis of ischemic heart disease. Endothelial function is impaired in patients with coronary spasm. Exercise training has been shown to improve endothelial function.

Increased urinary aldosterone excretion is associated with subcutaneous not visceral, adipose tissue area in obese individuals: a possible manifestation of dysfunctional subcutaneous adipose tissue.

Background: Aldosterone is reported to be associated with obesity and is a risk factor for metabolic syndrome. Metabolic abnormalities are more strongly associated with visceral adipose tissue (VAT) than with subcutaneous adipose tissue (SAT).

Objective: We examined whether aldosterone is more closely associated with VAT area than with SAT area in obese individuals.