Effect of rifampicin administration on CYP induction in a dermatomyositis patient with vasospastic angina attributable to nilmatrelvir/ritonavir-induced blood tacrolimus elevation: A case report.

Ritonavir (RTV), which is used in combination with nilmatrelvir (NMV) to treat coronavirus disease 2019 (COVID-19), inhibits cytochrome P450 (CYP) 3A, thereby increasing blood tacrolimus (TAC) levels through a drug-drug interaction (DDI). We experienced a case in which a DDI between the two drugs led to markedly increased blood TAC levels, resulting in vasospastic angina (VSA) and acute kidney injury (AKI). Rifampicin (RFP) was administered to induce CYP3A and promote TAC metabolism. A 60-year-old man with dermatomyositis who was taking 3 mg/day TAC contracted COVID-19. The patient started oral NMV/RTV therapy, and he was admitted to the hospital after 4 days because of chest pain and AKI. On day 5, his blood TAC level increased markedly to 119.8 ng/mL. RFP 600 mg was administered once daily for 3 days, and his blood TAC level decreased to the therapeutic range of 9.6 ng/mL on day 9, leading to AKI improvement. Transient complete atrioventricular block and nonsustained ventricular tachycardia were present during chest pain. In the coronary spasm provocation test, complete occlusion was observed in the right coronary artery, leading to a diagnosis of VSA. VSA and AKI are possible side effects of high blood TAC levels caused by DDI, and attention should be paid to cardiovascular side effects such as VSA and AKI associated with increased blood levels of TAC when it is used together with NMV/RTV. When blood levels of TAC increase, oral RFP can rapidly decrease TAC blood levels and potentially reduce its toxicity.

The impact of intraday glucose variability on coronary artery spasm in patients with dysglycemia.

Impaired glucose metabolism is associated with an increased risk of cardiovascular complications, and coronary artery spasm is thought to underlie the development of coronary artery disease. Intraday glucose variability (GV) accelerates oxidative stress and inflammatory cytokine release, but its impact on coronary artery spasm remains unclear. This study investigated the relationship between intraday GV and coronary artery spasm. The study included 50 patients with dysglycemia and suspected coronary spastic angina. GV was analyzed by 24-h monitoring of the blood glucose concentration using a flash glucose monitoring system. The mean amplitude of glycemic excursion (MAGE) was calculated as an index of GV. Coronary artery spasm was assessed using the intracoronary acetylcholine provocation test. Coronary spasm was defined as acetylcholine-induced total or subtotal coronary occlusion. Changes in vessel diameter in response to acetylcholine were evaluated with quantitative coronary angiography. Coronary artery spasms were observed in 21 patients (42%). MAGE was significantly higher in patients with spasms compared to those without spasms (127.5 ± 33.5 vs. 91.4 ± 37.6, p < 0.01). Regression analysis showed a positive correlation between MAGE levels and coronary diameter changes induced by acetylcholine (r = 0.47, p < 0.01). In multiple regression analysis, MAGE was independently associated with acetylcholine-induced coronary diameter change (ß = 0.47, p < 0.01). Intraday GV was associated with coronary artery spasm in patients with dysglycemia.

Prognostic impacts of Rho-kinase activity in circulating leucocytes in patients with vasospastic angina.

Aims: Rho-kinase activity in circulating leucocytes is a useful biomarker for diagnosis and disease activity assessment of vasospastic angina (VSA). The present study aimed to examine the long-term prognostic impact of Rho-kinase activity in circulating leucocytes in VSA patients. Methods and results: We prospectively enrolled 174 consecutive patients with VSA and 50 non-VSA patients, in whom we measured Rho-kinase activity in circulating leucocytes, and they were followed for a median of 16 months. The primary endpoint was cardiac events including cardiac death, non-fatal myocardial infarction, and hospitalization for unstable angina. During the follow-up period, cardiac events occurred in 10 VSA patients (5.7%) but in none of the non-VSA patients. When we divided VSA patients into two groups by a median value of their Rho-kinase activity, the Kaplan-Meier survival analysis showed a significantly worse prognosis in VSA patients with high Rho-kinase activity compared with those with low activity or non-VSA patients (log-rank; P < 0.05, respectively). Receiver-operating characteristic curve analysis showed that Rho-kinase activity value of 1.24 was the best cut-off level to predict cardiac events in VSA patients, and multivariable analysis showed that a value above the cut-off point had the largest hazard ratio to predict poor outcome in VSA patients [hazard ratio (95% confidence interval) 11.19 (1.41-88.95); P = 0.022]. Importantly, combination of the Japanese Coronary Spasm Association risk score and Rho-kinase activity significantly improved the prognostic impact in VSA patients as compared with either alone. Conclusion: Rho-kinase activity in circulating leucocytes is useful for prognostic stratification of VSA patients.

Medication adherence in patients with apparent resistant hypertension: findings from the SYMPATHY trial.

AIMS: Hypertension is only controlled in approximately 35% of the patients, which could be partially due to nonadherence. Recently, bioanalytical assessment of adherence to blood pressure (BP) lowering drugs has gaining interest. Our aim was to explore possible determinants of nonadherence in treatment resistant hypertension, assessed by objective screening for antihypertensive agents in serum. The secondary aim was to study the effect of adherence on the change in BP. METHODS: This project was a substudy of SYMPATHY; an open-label randomized-controlled trial to assess the effect of renal denervation on BP 6 months after treatment compared to usual care in patients with resistant hypertension. Stored serum samples were screened for antihypertensive agents to assess adherence at baseline and 6 months after intervention, using liquid chromatography-tandem mass spectrometry. Office and 24-h BP were measured on the same day as blood was sampled. Patients and physicians were unaware of adherence measurements. RESULTS: Ninety-eight baseline and 83 6-month samples were available for analysis. Sixty-eight percent [95% confidence interval (CI) 59-78%] of the patients was nonadherent (n = 67). For every onw pill more prescribed, 0.785 [95%CI 0.529-0.891] prescribed pill was less detected in blood. A decrease of one pill in adherence between baseline and 6 months was associated with a significant rise in office systolic BP of 4 (95%CI 0.230-8.932) mmHg. CONCLUSION: Objective measurement of BP lowering drugs in serum, as a tool to assess adherence, showed that nonadherence was very common in patients with apparent resistant hypertension. Furthermore, the assessment results were related to (changes in) blood pressure. Our findings provide direct and objective methodology to help the physician to understand and to improve the condition of apparent resistant hypertension.

Malondialdehyde-Modified Low Density Lipoprotein as Oxidative-Stress Marker in Vasospastic Angina Patients.

Vasospastic angina (VSA) is caused by endothelial dysfunction and hypercontraction of vascular smooth muscle cells. Although oxidative-stress can induce endothelial dysfunction, the relationship of VSA and the oxidative-stress marker malondialdehyde-modified low density lipoprotein (MDA-LDL) remains unclear. PURPOSE: Serum MDA-LDL was evaluated in candidate VSA patients.The subjects were 84 patients admitted to our hospital because of chest pain at rest. We stratified the patients into 3 groups; definite VSA, suspected VSA, and unlikely VSA according to a Japanese Circulation Society (JCS) guideline. The patients classified as definite VSA or suspected VSA were considered as "clinical VSA".Forty cases were classified as definite VSA, 35 as suspected VSA, and 9 as unlikely VSA. Thus, clinical VSA was the diagnosis in 75 cases. The patient characteristics showed that the average age of the patients was 60.2 years old (men, 61%). The serum MDA-LDL level of the clinical VSA group (126.3 ± 38.0 U/L) was significantly higher than the unlikely VSA group (98.7 ± 31.1 U/L). Serum MDA-LDL was positively correlated with total cholesterol (T-Chol), lowdensity lipoprotein cholesterol (LDL-C), triglycerides, and fasting blood glucose. Multivariate analysis showed that serum MDA-LDL was the most predictive marker for making a diagnosis of clinical VSA (Odds ratio 1.064, 95% confidence interval 1.014-1.145, P = 0.008). In a population with positive or borderline ECG change, the positive rate in the acetylcholine provocation test was significantly higher in the MDA-LDL higher group compared to the MDA-LDL lower group (81% versus 37%, P = 0.032).: Serum MDA-LDL might be a useful biomarker of VSA and have additional value for the diagnosis of clinical VSA.

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.Methods and Results:The study subjects comprised 410 patients (258 men, 152 women; mean age, 66.3±11.5) in whom intracoronary injection of acetylcholine was performed on suspicion of CSA.ALDH2genotyping was performed by direct application of the Taqman polymerase chain reaction system. Of the study subjects, 244 had CSA proven and 166 were non-CSA. The frequencies of male sex,ALDH2*2, alcohol flushing syndrome, TS, coronary organic stenosis, and plasma levels of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, and P=0.015, respectively) and that of high-density lipoprotein cholesterol lower (P=0.002) in the CSA than non-CSA group. Multivariable logistic regression analysis revealed thatALDH2*2and TS were significant risk factors for CSA (P<0.001 and P=0.002, respectively).ALDH2*2exacerbated TS risk for CSA more than the multiplicative effects of each. CONCLUSIONS: ALDH2*2synergistically exacerbates TS risk for CSA, probably through aldehydes.

High-temperature GC-MS-based serum cholesterol signatures may reveal sex differences in vasospastic angina.

Alterations of cholesterol metabolism are responsible for vasospastic angina and atherosclerosis. To comprehensively evaluate cholesterol metabolism, 18 sterols, including cholesterol, 6 cholesteryl esters (CEs), 3 cholesterol precursors, and 8 hydroxycholesterols (OHCs), were simultaneously analyzed using hybrid solid-phase extraction (SPE) purification coupled to high-temperature gas chromatography-mass spectrometry (HTGC-MS). Methanol-based hybrid SPE increased the selective extraction, and HTGC resulted in a good chromatographic resolution for the separation of lipophilic compounds. The limits of quantification of cholesterol and CEs ranged from 0.2 to 10.0 µg/ml, while OHCs and cholesterol precursors ranged from 0.01 to 0.10 µg/ml. Linearity as the correlation coefficient was higher than 0.99 with the exception of cholesteryl laurate, myristate, oleate, and linoleate (r² > 0.98). The precision (% coefficient of variation) and accuracy (% bias) ranged from 1.1 to 9.8% and from 75.9 to 125.1%, respectively. The overall recoveries of CEs ranged from 26.1 to 64.0%, and the recoveries of other sterols ranged from 83.8 to 129.3%. The cholesterol signatures showed sex differences in patients with vasospastic angina and may associate with 24-reductases. This technique can be useful for making clinical diagnoses and for an increased understanding of the pathophysiology of vasospastic angina.

Higher serum uric acid and lipoprotein(a) are correlated with coronary spasm.

It has been reported that a major cause of coronary vasospastic angina (VSA) is endothelial dysfunction of the coronary artery. On the other hand, some studies showed that serum uric acid and lipoprotein(a) are correlated with endothelial dysfunction. Thus, we examined whether uric acid and lipoprotein(a), are correlated with VSA. Four hundred forty-one patients with suspected VSA who underwent a coronary angiogram with acetylcholine provocation (ACh test) during an 8-year period were enrolled. We divided them into a VSA group, who showed coronary spasm by the ACh test, and an atypical chest pain (ACP) group, who showed negative ACh test. We compared serum markers between the two groups, including low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a), fibrinogen, total plasminogen activator inhibitor-1, and uric acid. Uric acid, hs-CRP, and lipoprotein(a) were significantly higher in the VSA group than in the ACP group (all P < 0.05) while there were no significant differences in the other parameters. Multivariate analyses identified uric acid and lipoprotein(a) as significant independent markers for VSA. Uric acid and lipoprotein(a) are correlated with VSA, and medical intervention to decrease uric acid and lipoprotein(a) might be effective in controlling VSA.

Elevated troponin levels in previously healthy children: value of diagnostic modalities and the importance of a drug screen.

BACKGROUND: Myocardial injury in previously healthy children is rare, with a wide range of aetiologies. It is increasingly being identified on the basis of elevated troponin levels during routine evaluation of cardiorespiratory symptoms. Establishing the aetiology remains challenging because of the lack of an accepted work-up algorithm. Our objective was to delineate the contribution of diagnostic modalities and troponin patterns towards the final diagnosis. METHODS: A retrospective chart review of previously healthy patients admitted to the Pediatric Cardiology Service with myocardial injury was carried out. Data analysed included echocardiograms, electrocardiograms, cardiac catheterisations, magnetic resonance imaging, drug screen tests, troponin values, and final diagnosis. RESULTS: A total of 32 patients were identified. The diagnoses were: myocarditis in 16 patients, vasospasm due to drug use in seven, myopericarditis in six, anomalous coronary artery origins in two, and Prinzmetal's angina in one patient. The electrocardiograms were abnormal in 27 of the 32 patients (84%), echocardiograms in 18 of the 32 patients (56%), cardiac magnetic resonance imaging in two of the four patients (50%), urine drug screen in five of the 25 patients (20%), and cardiac catheterisations in two of the 15 patients (13%). CONCLUSIONS: Myocarditis is the most common aetiology of myocardial injury in children. Clinical history remains the basic screening tool; drug screens help identify coronary vasospasms secondary to drug use (22% of our cohort). Patients with anomalous coronaries had exertional symptoms. Initial troponin levels and progression were not diagnostic or prognostic. Catheterisation is of limited value and did not change management. Magnetic resonance imaging with gadolinium enhancement is probably the most useful test when initial evaluation is not diagnostic.

Pharmacokinetics of intraluminally administered serum papaverine for spasm prophylaxis of the internal mammary artery.

BACKGROUND: Papaverine (Paveron N™ Linden Arzneimittel Vertrieb GmbH, Germany) is a widely used agent for preventing spasm in mammary artery preparations. The question addressed in this study is whether the intraluminal administration of papaverine can result in detectable absorption of the drug into the systemic arterial circulation. METHODS: In 15 patients (age 65 ± 6 years; body mass index 28.9 ± 3.7), an internal mammary artery (IMA) was prepared during coronary artery bypass grafting (CABG). A maximum of 3 mL of a 1 mg/1 mL diluted papaverine solution was injected intravascularly (intraluminally) for spasm prophylaxis. The IMA was closed proximally and distally with bulldog clamps. Blood samples were taken immediately after administration (T1), after 20 minutes (T2), and at the end of the operation (T3). Samples were measured in a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system consisting of a binary pump from Agilent (Waldbronn, Germany) coupled to a high-throughput screening (HTS) PAL injection system (CTC, Zwingen, Switzerland) and a tandem mass spectrometer (API 4000, AB Sciex, Darmstadt, Germany). Papaverine was analyzed in positive mode using an electrospray ion source. Quantitation was performed using Analyst 1.5 software (AB Sciex, Darmstadt, Germany). RESULTS: The newly developed LC-MS/MS method was successfully established for the detection of papaverine in plasma samples. The highest plasma papaverine levels were determined at time point T1 (mean 54.7 ± 39 ng/mL, range 16.6-179 ng/mL). The concentration was already halved 20 minutes after administration (T2) (mean 23.3 ± 2 ng/mL, range 4.6-118 ng/mL). Because of the short half-life and the hemodilution in the extracorporeal circulation, at the end of the operation papaverine (T3) had already fallen to just above the limit of detection (mean 4.1 ± 3.9 ng/mL, range 1.3-16.9 ng/mL). At time point T1, a significant negative correlation was determined between plasma levels and systemic diastolic, but not systolic, blood pressure. CONCLUSION: Papaverine was successfully determined systemically in plasma by LC-MS/MS after intraluminal administration in the IMA. Systemic circulatory effects are dependent on the detected quantity. Group size and the absence of a control group are considerable limitations.

Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina.

BACKGROUND: n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA. METHODS AND RESULTS: We enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ±â€¯37.7 µg/mL vs. 49.4 ±â€¯28.8 µg/mL, p = 0.015) and DHA (135.7 ±â€¯47.6 µg/mL vs. 117.4 ±â€¯37.6 µg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively. CONCLUSION: Our results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population.

Impairment of the extrusion transporter for asymmetric dimethyl-L-arginine: a novel mechanism underlying vasospastic angina.

A 37-year old male patient presented with frequent angina attacks (up to 40/day) largely resistant to classical vasodilator therapy. The patient showed severe coronary and peripheral endothelial dysfunction, increased platelet aggregation and increased platelet-derived superoxide production. The endothelial nitric oxide synthase (eNOS)-inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) reduced superoxide formation in platelets identifying "uncoupled" eNOS as a superoxide source. Oral L-arginine normalized coronary and peripheral endothelial dysfunction and reduced platelet aggregation and eNOS-derived superoxide production. Plasma concentrations of the endogenous NOS inhibitor asymmetric dimethyl-L-arginine (ADMA), representing an independent risk factor for cardiovascular disease, were normal in the patient. However, immediately after oral administration of cationic amino acid (CAA), plasma ADMA levels rose markedly, demonstrating increased ADMA efflux from intracellular stores. ADMA efflux from mononuclear cells of the patient was accelerated by CAA, but not neutral amino acids (NAA) demonstrating impairment of y(+)LAT (whose expression was found reduced in these cells). These data suggest that impairment of y(+)LAT may cause intracellular (endothelial) ADMA accumulation leading to systemic endothelial dysfunction. This may represent a novel mechanism underlying vasospastic angina and vascular dysfunction in general. Moreover, these new findings contribute to the understanding of the l-arginine paradox, the improvement of eNOS activity by oral L-arginine despite sufficient cellular l-arginine levels to ensure proper function of this enzyme.

Enhanced Rho-kinase activity in patients with vasospastic angina after the Great East Japan Earthquake.

BACKGROUND: It remains unclear whether disease activity of vasospastic angina (VSA) is altered during a disaster. METHODS AND RESULTS: Before and after the Great East Japan Earthquake, we examined Rho-kinase activity in circulating neutrophils of 11 VSA patients and their mental stress with the post-traumatic stress disorder (PTSD) questionnaire. Rho-kinase activity was significantly increased at 6 months after the Earthquake, and was returned to baseline level at 12 months. Importantly, percent change in Rho-kinase activity was significantly correlated with the PTSD score. CONCLUSIONS: These results indicate that the Rho-kinase activity of VSA patients was transiently enhanced associated with disaster-related mental stress.

Two questions for Kounis syndrome: can we use magnetic resonance imaging in the diagnosis and does ST elevation correlates with troponin levels?

Kounis syndrome (KS) is an acute coronary vasospasm after exposure to an allergen due to mast cell degranulation and existing mediators. Various drugs, conditions, and environmental exposures can cause KS. We presented 2 cases, 1 of whom had taken an antiflu drug (containing paracetamol, pseudoephedrine, and dextromethorphan). His electrocardiogram (ECG) showed inferior ST elevations (2 mm) with normal cardiac biomarkers. His cardiac magnetic resonance imaging showed hypokinesis and myocardial hibernation on apical septum and on the left ventricle. The second patient took a pill of naproxen sodium. The ECG showed 1-mm ST elevation in leads DII, V5, and V6. His troponin was markedly elevated. These cases showed that there seems to be no correlation with ECG and troponin levels in KS. In addition, for patients in whom KS type 1 is expected without troponin elevation, noninvasive cardiac magnetic resonance imaging study seems to be appropriate for the diagnosis of KS.

Monocyte to HDL ratio: a novel marker of resistant hypertension in CKD patients.

BACKGROUND: Inflammation, oxidative stress (OS), atherosclerosis and resistant hypertension (RH) are common features of chronic kidney disease (CKD) leading to a higher risk of death from cardiovascular disease. These effects seem to be modulated by impaired anti-oxidant, anti-inflammatory and reverse cholesterol transport actions of high-density lipoprotein cholesterol (HDL). HDL prevents and reverses monocyte recruitment and activation into the arterial wall and impairs endothelial adhesion molecule expression. Recently, monocyte count to HDL-cholesterol ratio (MHR) has emerged as a potential marker of inflammation and OS, demonstrating to be relevant in CKD. Our research was aimed to assess, for the first time, its reliability in RH. METHODS: We performed a retrospective study on 214 patients with CKD and arterial hypertension who were admitted between January and June 2019 to our Department, 72 of whom were diagnosed with RH. RESULTS: MHR appeared inversely related to eGFR (ρ = - 0.163; P = 0.0172). MHR was significantly higher among RH patients compared to non-RH ones (12.39 [IQR 10.67-16.05] versus 7.30 [5.49-9.06]; P < 0.0001). Moreover, MHR was significantly different according to the number of anti-hypertensive drugs per patient in the whole study cohort (F = 46.723; P < 0.001) as well as in the non-RH group (F = 14.191; P < 0.001). Moreover, MHR positively correlates with diabetes mellitus (ρ = 0.253; P = 0.0002), white blood cells (ρ = 0.664; P < 0.0001) and C-reactive protein (ρ = 0.563; P < 0.0001). CONCLUSIONS: MHR may be a reliable biomarker due to the connection between HDL and monocytes. Our study suggests that MHR is linked with the use of multiple anti-hypertensive therapy and resistant hypertension in CKD patients, and can be a useful ratio to implement appropriate treatment strategies.

Can mean platelet volume predict coronary vasospasm?

Mean platelet volume (MPV) is an index of platelet function that reflects platelet production rate and sensitivity to activation. The relationship between MPV and coronary vasospasm has not been previously studied. In this study, we aimed to evaluate this relationship. A total of 696 patients (age 55.20 ± 12.26, male 46.4%, female 53.6%) with typical or atypical angina who underwent diagnostic coronary angiography (CAG) and an acetylcholine (Ach)-provocation test were enrolled. Each patient was assigned to either an Ach-induced coronary vasospasm group (n = 183) or a control group (n = 513). We compared MPV between the two groups. MPV and the platelet count showed a negative correlation (r = -0.289, p < 0.001). MPV was higher in the Ach-induced coronary vasospasm group than in the control group (9.03 ± 1.37 fl and 8.69 ± 1.25 fl, respectively, p = 0.002). In multivariate analysis, MPV independently predicted Ach-induced coronary vasospasm (OR = 1.188, p = 0.018). This study identified high MPV as an independent risk factor for Ach-induced coronary vasospasm.

Admission serum potassium levels and prognosis of vasospastic angina.

Hypokalemia is a common electrolyte disturbance and is related to poor prognosis in patients with cardiovascular disease. However, the role of hypokalemia in patients with vasospastic angina (VSA) has not yet been studied. The present study enrolled 1454 patients diagnosed with VSA according to ergonovine provocation test results and available admission serum potassium data. The primary outcome was a composite of cardiac death, acute coronary syndrome, and new-onset life-threatening arrhythmia. Based on a hypokalemia definition as serum potassium concentration ≤ 3.5 mEq/L, the hypokalaemia group included 70 patients (4.8%). The median potassium levels were 3.4 mEq/L [interquartile range (IQR) 3.3-3.5] in the hypokalemia group and 4.1 mEq/L (IQR 3.9-4.3) in the no-hypokalemia group. The median follow-up duration was 764 days. Primary outcomes occurred in seven patients (10.0%) in the hypokalemia group and 51 patients (3.7%) in the no-hypokalemia group. The Kaplan-Meier analysis showed a higher cumulative incidence of primary outcomes in the hypokalemia group compared to that in the no-hypokalemia group (log-rank P = 0.014). Multivariate Cox regression analysis also showed that hypokalemia was an independent predictor of primary outcomes. In conclusion, hypokalemia at admission was associated with adverse clinical outcomes in VSA.

Interactions among gender, age, hypertension and C-reactive protein in coronary vasospasm.

BACKGROUND: Coronary vasospasm (CVsp) has been reported to be an inflammatory disease, reflected by elevated high-sensitivity C-reactive protein (hs-CRP). We investigated the interactions among gender, age, hypertension and hs-CRP in patients with CVsp. MATERIALS AND METHODS: We retrospectively examined 722 Taiwanese patients with or without CVsp during an 8-year period. None of the patients had obstructive coronary artery disease. Serum hs-CRP levels were examined in a subset of 375 patients to evaluate the interactions of hs-CRP with gender, age, smoking and hypertension in the development of CVsp. RESULTS: In women, only the highest hs-CRP tertile (> 3 mg L⁻¹) was independently associated with CVsp. In men, age > 58 years and the highest hs-CRP tertile were independently associated with CVsp. In women, elevated risk was only demonstrated in patients ≤ 58 years of age with hs-CRP levels in the highest tertile. In men, a positively monotonic trend was demonstrated between hs-CRP levels and CVsp in those > 58 years of age. The odds ratios of CVsp in both women and men with hs-CRP in the highest tertile reduced from 6·01 to 1·48 and 6·35-2·69 respectively, if they had hypertension. CONCLUSION: The relationship between hs-CRP and CVsp differed between men and women. Our findings that there is a non-threshold model in men and a threshold model in women provide evidence that more smokers in men (life-style) and age (induction time) contribute to the natural history of CVsp development. The negative effect of hypertension on CVsp suggests that the pathogenesis of CVsp differs from that of coronary atherosclerosis.

Ischemia-modified albumin: is it a reliable diagnostic and prognostic marker for myocardial ischemia in real clinical practice?

OBJECTIVES: We investigated whether ischemia-modified albumin (IMA), a novel biomarker of acute myocardial ischemia, is reliable for diagnosing ischemic chest pain and predicting future cardiac events in clinical practice. METHODS: We enrolled 390 patients (age 61.7 +/- 39.9 years) who arrived at the emergency department within 6 h of pain onset. We compared serum IMA levels of patients with ischemic chest pain (ICP) to those with nonischemic chest pain (NICP). RESULTS: NICP was diagnosed in 162 patients and ICP in 205 patients. Median serum IMA levels did not differ between the NICP (99.0 U/ml; 95% confidence interval, 98.2-101.2 U/ml) and the ICP group (99.0 U/ml; 95% confidence interval, 99.4-102.6 U/ml; p = 0.320). During a 2-year follow-up, adverse cardiac events including cardiac death, myocardial infarction and recurrent angina occurred in 25 of 205 patients (12.2%) in the ICP group, but IMA was not predictive of cardiac events. CONCLUSIONS: IMA was neither able to discriminate acute chest pain due to myocardial ischemia from that of other origin nor to predict cardiac events. Therefore, use of serum IMA levels for triage of patients with acute chest pain does not seem effective in clinical practice.