Apparent treatment-resistant hypertension among ambulatory hypertensive patients: a cross-sectional study from 13 general hospitals

Background/Aims@#To examine the prevalence and clinical characteristics of apparent treatment-resistant hypertension among ambulatory hypertensive patients. @*Methods@#We enrolled adult ambulatory hypertensive patients at 13 well-qualified general hospitals in Korea from January to June 2012. Apparent resistant hypertension was defined as an elevated blood pressure > 140/90 mmHg with the use of three antihypertensive agents, including diuretics, or ≥ 4 antihypertensives, regardless of the blood pressure. Controlled hypertension was defined as a blood pressure within the target using three antihypertensives, including diuretics. @*Results@#Among 16,915 hypertensive patients, 1,172 (6.9%) had controlled hypertension, and 1,514 (8.9%) had apparent treatment-resistant hypertension. Patients with apparent treatment-resistant hypertension had an earlier onset of hypertension (56.8 years vs. 58.8 years, p = 0.007) and higher body mass index (26.3 kg/m2 vs. 24.9 kg/m2, p < 0.001) than those with controlled hypertension. Drug compliance did not differ between groups. In the multivariable analysis, earlier onset of hypertension (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99; p < 0.001) and the presence of comorbidities (OR, 2.06; 95% CI, 1.27 to 3.35; p < 0.001), such as diabetes mellitus, ischemic heart disease, heart failure, and chronic kidney disease, were independent predictors. Among the patients with apparent treatment-resistant hypertension, only 5.2% were receiving ≥ 2 antihypertensives at maximally tolerated doses. @*Conclusions@#Apparent treatment-resistant hypertension prevalence is 8.9% among ambulatory hypertensive patients in Korea. An earlier onset of hypertension and the presence of comorbidities are independent predictors. Optimization of medical treatment may reduce the rate of apparent treatment-resistant hypertension.

Apparent treatment-resistant hypertension among ambulatory hypertensive patients: a cross-sectional study from 13 general hospitals

Background/Aims@#To examine the prevalence and clinical characteristics of apparent treatment-resistant hypertension among ambulatory hypertensive patients. @*Methods@#We enrolled adult ambulatory hypertensive patients at 13 well-qualified general hospitals in Korea from January to June 2012. Apparent resistant hypertension was defined as an elevated blood pressure > 140/90 mmHg with the use of three antihypertensive agents, including diuretics, or ≥ 4 antihypertensives, regardless of the blood pressure. Controlled hypertension was defined as a blood pressure within the target using three antihypertensives, including diuretics. @*Results@#Among 16,915 hypertensive patients, 1,172 (6.9%) had controlled hypertension, and 1,514 (8.9%) had apparent treatment-resistant hypertension. Patients with apparent treatment-resistant hypertension had an earlier onset of hypertension (56.8 years vs. 58.8 years, p = 0.007) and higher body mass index (26.3 kg/m2 vs. 24.9 kg/m2, p < 0.001) than those with controlled hypertension. Drug compliance did not differ between groups. In the multivariable analysis, earlier onset of hypertension (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99; p < 0.001) and the presence of comorbidities (OR, 2.06; 95% CI, 1.27 to 3.35; p < 0.001), such as diabetes mellitus, ischemic heart disease, heart failure, and chronic kidney disease, were independent predictors. Among the patients with apparent treatment-resistant hypertension, only 5.2% were receiving ≥ 2 antihypertensives at maximally tolerated doses. @*Conclusions@#Apparent treatment-resistant hypertension prevalence is 8.9% among ambulatory hypertensive patients in Korea. An earlier onset of hypertension and the presence of comorbidities are independent predictors. Optimization of medical treatment may reduce the rate of apparent treatment-resistant hypertension.

Long-term Prognosis and Clinical Characteristics of Patients with Newly Diagnosed Diabetes Mellitus Detected after First Acute Myocardial Infarction: from KAMIR-NIH Registry

BACKGROUND AND OBJECTIVES@#After the first acute myocardial infarction (AMI), a considerable proportion of patients are newly diagnosed with diabetes mellitus (DM). However, in AMI, controversy remains regarding the disparity in prognosis between previously diagnosed DM (known-DM) and newly diagnosed DM (new-DM).@*METHODS@#The study included 10,455 patients with AMI (non-DM, 6,236; new-DM, 659; known-DM, 3,560) admitted to one of 15 participating centers in Korea between November 2011 and January 2016 (average follow-up, 523 days). We compared the characteristics and clinical course of patients with known-DM and those with new- or non-DM.@*RESULTS@#Compared to patients with known-DM, those with new-DM or non-DM were younger, more likely to be male, and less likely to have hypertension, dyslipidemia, prior stroke, angina, or myocardial infarction. Compared to patients with new-DM or non-DM (reference), those with known-DM had higher risks of major adverse cardiac events (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.06–1.35; p=0.004), cardiac death (HR, 1.26; 95% CI, 1.01–1.57; p=0.042), and congestive heart failure (HR, 1.58; 95% CI, 1.20–2.08). Unlike known-DM, new-DM did not increase the risk of cardiac events (including death).@*CONCLUSIONS@#Known-DM was associated with a significantly higher risk of cardiovascular events after AMI, while new-DM had a similar risk of cardiac events as that noted for non-DM. There were different cardiovascular outcomes according to diabetes status in patients with AMI.

Long-term Prognosis and Clinical Characteristics of Patients with Newly Diagnosed Diabetes Mellitus Detected after First Acute Myocardial Infarction: from KAMIR-NIH Registry

BACKGROUND AND OBJECTIVES: After the first acute myocardial infarction (AMI), a considerable proportion of patients are newly diagnosed with diabetes mellitus (DM). However, in AMI, controversy remains regarding the disparity in prognosis between previously diagnosed DM (known-DM) and newly diagnosed DM (new-DM). METHODS: The study included 10,455 patients with AMI (non-DM, 6,236; new-DM, 659; known-DM, 3,560) admitted to one of 15 participating centers in Korea between November 2011 and January 2016 (average follow-up, 523 days). We compared the characteristics and clinical course of patients with known-DM and those with new- or non-DM. RESULTS: Compared to patients with known-DM, those with new-DM or non-DM were younger, more likely to be male, and less likely to have hypertension, dyslipidemia, prior stroke, angina, or myocardial infarction. Compared to patients with new-DM or non-DM (reference), those with known-DM had higher risks of major adverse cardiac events (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.06–1.35; p=0.004), cardiac death (HR, 1.26; 95% CI, 1.01–1.57; p=0.042), and congestive heart failure (HR, 1.58; 95% CI, 1.20–2.08). Unlike known-DM, new-DM did not increase the risk of cardiac events (including death). CONCLUSIONS: Known-DM was associated with a significantly higher risk of cardiovascular events after AMI, while new-DM had a similar risk of cardiac events as that noted for non-DM. There were different cardiovascular outcomes according to diabetes status in patients with AMI.

Prognostic value of total triiodothyronine and free thyroxine levels for the heart failure in patients with acute myocardial infarction

BACKGROUND/AIMS: Although a low triiodothyronine (T3) state is closely associated with heart failure (HF), it is uncertain whether total T3 levels on admission is correlated with the clinical outcomes of acute myocardial infarction (AMI). The aim of this study is to investigate the prognostic value of total T3 levels for major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with AMI undergone percutaneous coronary intervention (PCI). METHODS: A total of 765 PCI-treated AMI patients (65.4 ± 12.6 years old, 215 women) between January 2012 and July 2014 were included and 1-year MACCEs were analyzed. We assessed the correlation of total T3 and free thyroxine (fT4) with prevalence of 1-year MACCEs and the predictive values of total T3, fT4, and the ratio of total T3 to fT4 (T3/fT4), especially for HF requiring re-hospitalization. RESULTS: Thirty patients (3.9%) were re-hospitalized within 12 months to control HF symptoms. Total T3 levels were lower in the HF group than in the non-HF group (84.32 ± 21.04 ng/dL vs. 101.20 ± 20.30 ng/dL, p < 0.001). Receiver operating characteristic curve analysis showed the cut-offs of total T3 levels (≤ 85 ng/dL) and T3/fT4 (≤ 60) for HF (area under curve [AUC] = 0.734, p < 0.001; AUC = 0.774, p < 0.001, respectively). In multivariate analysis, lower T3/fT4 was an independent predictor for 1-year HF in PCI-treated AMI patients (odds ratio, 1.035; 95% confidential interval, 1.007 to 1.064; p = 0.015). CONCLUSIONS: Lower levels of total T3 were well correlated with 1-year HF in PCI-treated AMI patients. The T3/fT4 levels can be an additional marker to predict HF.

ST segment

The ST segment corresponds to the plateau phase of ventricular repolarization, i.e., phase 2 of the action potential. Heightened awareness of the characteristic patterns of ST segment changes is vital to quickly identifying life-threatening disorders. The differential diagnosis of ST segment elevation includes four major processes: ST segment elevation myocardial infarction (STEMI); early repolarization; pericarditis; and ST elevation secondary to an abnormality of the QRS complex (left bundle branch block, left ventricular hypertrophy, or preexcitation). Other processes that may be associated with ST elevation include hyperkalemia, pulmonary embolism, and Brugada syndrome. Two particular patterns of ST segment depression reflect STEMI rather than non-ST-segment elevation acute coronary syndrome: ST segment depression that is reciprocal to a subtle and sometimes overlooked ST-segment elevation, and ST segment depression that is maximal in leads V₁-V₃, suggesting true posterior infarction. The clinical setting and specific electrocardiographic criteria often allow identification of the cause.

Antiplatelet Therapy Combinations and Thrombogenicity in Patients with Non-Valvular Atrial Fibrillation

BACKGROUND AND OBJECTIVES: Combination antiplatelet therapy reduces the risk of ischemic stroke compared with aspirin monotherapy in non-valvular atrial fibrillation (NVAF) patients. The underlying mechanism, however, remains unclear. In addition, the association between platelet inhibition and thrombogenicity in NVAF has not been evaluated. SUBJECTS AND METHODS: We randomized 60 patients with NVAF that were taking 100 mg of aspirin daily (>1 month) to adding 75 mg of clopidogrel daily (CLPD group), 100 mg of cilostazol twice daily (CILO group), or 1000 mg of omega-3 polyunsaturated fatty acid twice daily (PUFA group). Biomarkers (von Willebrand factor antigen [vWF:Ag], fibrinogen, D-dimer, and high-sensitivity C-reactive protein [hs-CRP]) and platelet reactivity (PR), which were the levels stimulated by adenosine diphosphate (ADP), thrombin-receptor agonist peptide, collagen, and arachidonic acid, were measured at baseline and 30-day follow-up. RESULTS: Combination antiplatelet therapy significantly reduced vWF:Ag and fibrinogen levels (7.7 IU/dL, p=0.015 and 15.7 mg/dL, p=0.005, respectively), but no changes were found in D-dimer and hs-CRP levels. The CLPD and CILO groups showed fibrinogen and vWF:Ag level reductions (24.9 mg/dL, p=0.015 and 9.3 IU/dL, p=0.044, respectively), whereas the PUFA group did not show any differences in biomarkers. Irrespective of regimen, the changes in fibrinogen and vWF:Ag levels were mainly associated with the change in ADP-mediated PR (r=0.339, p=0.008 and r=0.322, p=0.012, respectively). CONCLUSION: In patients with NVAF, combination antiplatelet therapy showed reductions for vWF:Ag and fibrinogen levels, which may be associated with the inhibitory levels of ADP-mediated PR. The clinical implications of these findings need to be evaluated in future trials.

A Case of Cardiac Arrest due to Multivessel, Diffuse Coronary Spasm in Moyamoya Disease / 고신대학교의과대학학술지

Moyamoya disease is characterized by progressive stenosis of the distal portion of the internal carotid arteries and fragile collateral vessels in the brain. The precise pathogenesis is still not known. Although extracranial vessel involvement is very rare, coronary arterial involvement has recently been reported. Here, we report a case of diffuse, multivessel coronary spasm leading to cardiac arrest and myocardial infarction in a 47-year-old man with moyamoya disease with no underlying emotional or physical stress.

Osmotic Demyelination Syndrome Resulting from an Unexpected Response to Tolvaptan in a Patient with Heart Failure / 대한내과학회지

Hyponatremia is commonly encountered in patients with heart failure and has a poor prognosis. Tolvaptan, a novel selective vasopressin V2 receptor blocker, has received attention as an effective drug for treating the syndrome of inappropriate antidiuretic hormone secretion and hypervolemic hyponatremia. However, the safety of tolvaptan in the treatment of hyponatremia is not clear. We experienced a 78-year-old woman with a history of heart failure, atrial fibrillation, and hyponatremia who developed osmotic demyelination syndrome as an unexpected response to treatment with tolvaptan.

Prognostic value of computed tomographic coronary angiography and exercise electrocardiography for cardiovascular events

BACKGROUND/AIMS: This study is a head-to-head comparison of predictive values for long-term cardiovascular outcomes between exercise electrocardiography (ex-ECG) and computed tomography coronary angiography (CTCA) in patients with chest pain. METHODS: Four hundred and forty-two patients (mean age, 56.1 years; men, 61.3%) who underwent both ex-ECG and CTCA for evaluation of chest pain were included. For ex-ECG parameters, the patients were classified according to negative or positive results, and Duke treadmill score (DTS). Coronary artery calcium score (CACS), presence of plaque, and coronary artery stenosis were evaluated as CTCA parameters. Cardiovascular events for prognostic evaluation were defined as unstable angina, acute myocardial infarction, revascularization, heart failure, and cardiac death. RESULTS: The mean follow-up duration was 2.8 ± 1.1 years. Fifteen patients experienced cardiovascular events. Based on pretest probability, the low- and intermediate-risks of coronary artery disease were 94.6%. Odds ratio of CACS > 40, presence of plaque, coronary stenosis ≥ 50% and DTS ≤ 4 were significant (3.79, p = 0.012; 9.54, p = 0.030; 6.99, p < 0.001; and 4.58, p = 0.008, respectively). In the Cox regression model, coronary stenosis ≥ 50% (hazard ratio, 7.426; 95% confidence interval, 2.685 to 20.525) was only significant. After adding DTS ≤ 4 to coronary stenosis ≥ 50%, the integrated discrimination improvement and net reclassification improvement analyses did not show significant. CONCLUSIONS: CTCA was better than ex-ECG in terms of predicting long-term outcomes in low- to intermediate-risk populations. The predictive value of the combination of CTCA and ex-ECG was not superior to that of CTCA alone.

Erratum to: Additive Beneficial Effects of Valsartan Combined with Rosuvastatin in the Treatment of Hypercholesterolemic Hypertensive Patients

In this article, on page 230, Fig. 2A needs to be corrected.

The Effect of Cilostazol on Arterial Stiffness in Patients Undergoing Percutaneous Coronary Intervention / 대한내과학회지

BACKGROUND/AIMS: Increased arterial stiffness is a well-known risk factor for cardiovascular disease. Cilostazol, a phosphodiesterase type 3 inhibitor, is a unique antiplatelet agent with vasodilatory and vasoprotective effects. Therefore, we hypothesized that cilostazol may affect arterial stiffness. METHODS: We enrolled 161 patients (112 males; mean age, 63 years) who had undergone percutaneous coronary intervention (PCI) for ischemic heart disease. The brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), rAI adjusted for a heart rate of 75 beats/min (rAI75), central systolic blood pressure (cSBP), and central pulse pressure (cPP), were measured at baseline and at the 30-day follow-up. Parameter changes were compared between the cilostazol group (n = 51) and the control group (n = 110). RESULTS: In the cilostazol group, the values for rAI, cSBP, and cPP all improved after 30 days, while the control group displayed no significant interval changes in these parameters. The changes in rAI75 and baPWV did not differ significantly between the two groups. The changes in rAI, cSBP, and cPP were related to brachial systolic blood pressure, brachial diastolic blood pressure, heart rate, and the use of cilostazol and beta-blockers. In a multivariate analysis, the use of cilostazol was identified an independent factor associated with changes in rAI, cSBP, and cPP. CONCLUSIONS: The addition of cilostazol to conventional antiplatelet therapy in patients undergoing PCI may be associated with improvements in rAI, cSBP, and cPP, but not in rAI75 or baPWV. Therefore, the effects of cilostazol might be related to an increased heart rate.

Additive Beneficial Effects of Valsartan Combined with Rosuvastatin in the Treatment of Hypercholesterolemic Hypertensive Patients

BACKGROUND AND OBJECTIVES: We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. SUBJECTS AND METHODS: Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. RESULTS: A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. CONCLUSION: Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.

Comparison of Computed Tomography Coronary Angiography and Exercise ECG Test for Diagnostic Accuracy in Real-World Practice / 대한내과학회지

BACKGROUND/AIMS: The exercise ECG test (XECG) and computed tomography coronary angiography (CTCA) have been used widely in initial evaluations of coronary artery disease (CAD) in real-world practice. In this study, we compared the diagnostic power of CTCA and XECG, based on conventional coronary angiography (CCA). METHODS: We enrolled 589 consecutive patients retrospectively who had been examined with both XECG and CTCA for the evaluation of CAD in outpatient clinics. Significant stenosis was defined as more than 50% diameter stenosis. Triage to CCA and/or revascularization treatment (RT) by the results of XECG and CTCA and the diagnostic accuracy of both exams, based on CCA, were investigated. RESULTS: In the 589 patients, 107 (19%) were triaged to CCA for further evaluation; in 77 (12.8%) significant stenosis was detected on CCA. Also, 65 (11%) patients underwent RT. In the CTCA results, 120 patients had significant stenosis. Of them, 58 (48%) and 75 (62%) patients were triaged to RT and CCA, respectively. Based on the XECG, 115 positive patients were triaged to RT and CCA (23 [20%]/41 [35%]). Among 107 patients with CCA, the sensitivity, specificity, positive predictive value, and negative predictive value for significant stenosis on CCA of CTCA were 89.9%, 74.0%, 90.6%, and 71.4%, respectively, and those of XECG were 50.0, 67.9, 78.0, and 37.3, respectively. The kappa value of CCA and CTCA was 0.62 (p < 0.001) and that of CCA and XECG was 0.145 (p = 0.113). CONCLUSIONS: In real-world practice, CCA was decided on more frequently, based on CTCA. CTCA showed better diagnostic accuracy than XECG.

A Case of Complete Recovery from Late Insidious Type of Acute Phosphate Nephropathy / 대한내과학회지

The widespread use of colonoscopy for early detection of colorectal pathology has increased the use of osmotic laxatives for colonic cleansing. Among these, oral sodium phosphate preparations can cause renal insufficiency through the development of acute phosphate nephropathy. Acute phosphate nephropathy can be distinguished as early symptomatic and late insidious patterns. Patients whose presentation is insidious are easily overlooked and can progress to chronic kidney disease. We report a case of complete recovery from the late insidious type of acute phosphate nephropathy.

Permanent Pacemaker Implantation in a Patient with MELAS Syndrome / 대한내과학회지

A 35-year-old male patient with heart and renal failure and pneumonia was transferred to our department due to recurrent cardiac standstill with syncope. He had been diagnosed as and treated for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome for the past 3 years. Electrocardiography (ECG) showed the Wolff-Parkinson-White pattern, and an echocardiogram showed hypertrophic cardiomyopathy. He developed syncopal attacks intermittently, and ECG monitoring showed intermittent bradycardia. His Holter monitoring showed several episodes of 5-16 seconds of sinus arrest. We conducted an electrophysiological study to evaluate the arrhythmia. During atrial and ventricular extra-stimuli, cardiac standstill developed several times, and the duration of pauses varied from 2.5 to 5.5 seconds. Abrupt asystolic events also developed accompanying syncopal attacks that were not related to the extra-stimuli. We decided to implant a permanent pacemaker. The patient's syncopal episodes disappeared after implantation of a DDD type pacemaker.

Stress-Induced Cardiomyopathy as a Complication of Permanent Pacemaker Implantation / 대한내과학회지

Stress-induced cardiomyopathy is a disease characterized by acute transient left ventricular dysfunction following exposure to stressful situations. We encountered an 80-year-old woman with complete atrioventricular block and normal LV systolic function. After permanent pacemaker implantation, electrocardiogram showed inverted T-waves in precordial leads. Follow-up echocardiographic findings indicated dyskinesia of the apical wall. Final diagnosis was stress-induced cardiomyopathy associated with a physically stressful condition (i.e., pacemaker implantation).

Permanent Pacemaker Implantation in a Patient with Cardiac Syncope Associated with Glossopharyngeal Neuralgia / 대한내과학회지

Glossopharyngeal neuralgia is a rare disease that is characterized by sharp pain in the posterior pharynx, tonsils, and larynx, triggered by swallowing. Glossopharyngeal neuralgia can trigger bradycardia or asystole, which can induce life-threatening cardiac syncope. A 55-year-old male was admitted with severe paroxysmal pain in his left jaw and ear, followed by asystole and syncope. We report a patient with cardiac syncope associated with glossopharyngeal neuralgia treated with a permanent pacemaker.

Permanent Pacemaker Implantation in a Patient with Cardiac Syncope Associated with Glossopharyngeal Neuralgia / 대한내과학회지

Glossopharyngeal neuralgia is a rare disease that is characterized by sharp pain in the posterior pharynx, tonsils, and larynx, triggered by swallowing. Glossopharyngeal neuralgia can trigger bradycardia or asystole, which can induce life-threatening cardiac syncope. A 55-year-old male was admitted with severe paroxysmal pain in his left jaw and ear, followed by asystole and syncope. We report a patient with cardiac syncope associated with glossopharyngeal neuralgia treated with a permanent pacemaker.

Stress-Induced Cardiomyopathy as a Complication of Permanent Pacemaker Implantation / 대한내과학회지

Stress-induced cardiomyopathy is a disease characterized by acute transient left ventricular dysfunction following exposure to stressful situations. We encountered an 80-year-old woman with complete atrioventricular block and normal LV systolic function. After permanent pacemaker implantation, electrocardiogram showed inverted T-waves in precordial leads. Follow-up echocardiographic findings indicated dyskinesia of the apical wall. Final diagnosis was stress-induced cardiomyopathy associated with a physically stressful condition (i.e., pacemaker implantation).