Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement

Dyslipidemia in patients with diabetes is an important treatment target as a modifiable risk factor for cardiovascular disease (CVD). Although the primary treatment goal for dyslipidemia is to control low-density lipoprotein cholesterol (LDL-C), achieving this goal remains suboptimal according to recent studies. It is important to set the target goal for LDL-C control based on an accurate risk assessment for CVD. Here, we summarize the latest evidence on lipid management in patients with diabetes and present a consensus of the Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis on the treatment goals of LDL-C according to the duration of diabetes, presence of CVD, target organ damage, or major cardiovascular risk factors. In patients with type 2 diabetes mellitus (T2DM) and CVD, an LDL-C goal of <55 mg/dL and a reduction in LDL-C level by 50% or more from the baseline is recommended. For the primary prevention of CVD in patients with T2DM with a duration of diabetes ≥10 years, major cardiovascular risk factors, or target organ damage, an LDL-C goal of <70 mg/dL is recommended. In patients with T2DM with a duration of diabetes <10 years and no major cardiovascular risk factors, an LDL-C goal of <100 mg/dL is recommended.

Sex Differences in Coronary Artery Disease: Insights From the KoRean wOmen’S chest pain rEgistry (KoROSE)

Interest in sex differences in coronary artery disease (CAD) has been steadily increasing.Concurrently, most of the data on these differences have primarily been Western-oriented.The KoRean wOmen’S chest pain rEgistry (KoROSE), started in 2011, has since published numerous research findings. This review aims to summarize the reported differences between men and women in CAD, integrating data from KoROSE. Cardiovascular risk in postmenopausal women escalates dramatically due to the decrease in estrogen levels, which normally offer cardiovascular protective effects. Lower estrogen levels can lead to abdominal obesity, insulin resistance, increased blood pressure, and endothelial dysfunction in older women. Upon analyzing patients with CAD, women are typically older and exhibit more cardiovascular risk factors than men. Diagnosing CAD in women tends to be delayed due to their symptoms being more atypical than men’s. While in-hospital outcome was similar between sexes, bleeding complications after percutaneous coronary intervention occur more frequently in women. The differences in long-term prognosis for CAD patients between men and women are still a subject of ongoing debate. Pregnancy and reproductive factors also play a significant role as risk factors for cardiovascular disease in women. A notable sex disparity exists, with women found to use fewer cardiovascular protective drugs and undergo fewer interventional or surgical procedures than men. Additionally, women participate less frequently than men in clinical research. Through concerted efforts to increase awareness of sex differences and mitigate sex disparity, personalized treatment can be provided. This approach can ultimately improve patient prognosis.

Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement

Dyslipidemia in patients with diabetes is an important treatment target as a modifiable risk factor for cardiovascular disease (CVD). Although the primary treatment goal for dyslipidemia is to control low-density lipoprotein cholesterol (LDL-C), achieving this goal remains suboptimal according to recent studies. It is important to set the target goal for LDL-C control based on an accurate risk assessment for CVD. Here, we summarize the latest evidence on lipid management in patients with diabetes and present a consensus of the Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis on the treatment goals of LDL-C according to the duration of diabetes, presence of CVD, target organ damage, or major cardiovascular risk factors. In patients with type 2 diabetes mellitus (T2DM) and CVD, an LDL-C goal of <55 mg/dL and a reduction in LDL-C level by 50% or more from the baseline is recommended. For the primary prevention of CVD in patients with T2DM with a duration of diabetes ≥10 years, major cardiovascular risk factors, or target organ damage, an LDL-C goal of <70 mg/dL is recommended. In patients with T2DM with a duration of diabetes <10 years and no major cardiovascular risk factors, an LDL-C goal of <100 mg/dL is recommended.

Interventions for Adherence Improvement in the Primary Prevention of Cardiovascular Diseases:Expert Consensus Statement

In primary prevention for cardiovascular diseases, there are significant barriers to adherence including freedom from symptoms, long latency for therapeutic benefits, life-long duration of treatment, and need for combined lifestyle changes. However, to implement more systematic approaches, the focus on adherence improvement needs to be shifted away from patient factors to the effects of the treatment team and healthcare system. In addition to conventional educational approaches, more patient-oriented approaches such as patientcentered clinical communication skills, counseling using motivational strategies, decisionmaking by patient empowerment, and a multi-disciplinary team approach should be developed and implemented. Patients should be involved in a program of self-monitoring, self-management, and active counseling. Because most effective interventions on adherence improvement demand greater resources, the health care system and educational or training system of physicians and healthcare staff need to be supported for systematic improvement.

Lifestyle Modification in the Management of Metabolic Syndrome:Statement From Korean Society of CardioMetabolic Syndrome (KSCMS)

With the recent rapid increase in obesity worldwide, metabolic syndrome (MetS) has gained significant importance. MetS is a cluster of obesity-related cardiovascular risk factors including abdominal obesity, atherogenic dyslipidemia, high blood pressure and impaired glucose tolerance. MetS is highly prevalent and strongly associated with an increased risk of developing diabetes and cardiovascular disease, putting a great burden on human society. Therefore, it is very important to reduce MetS risk, which can improve patients’cardiovascular prognosis. The primary and most effective strategy to control each component of MetS is lifestyle change such as losing body weight, keeping regular exercise, adopting a healthy diet, quitting smoking and alcohol drinking in moderation. Many studies have shown that lifestyle modification has improved all components of MetS, and reduces the incidence of diabetes and cardiovascular disease. Here, the Korean Society of CardioMetabolic Syndrome has summarized specific and practical methods of lifestyle modification in the management of MetS in the healthcare field.

Elevated On-Treatment Diastolic Blood Pressure and Cardiovascular Outcomes in the Presence of Achieved Systolic Blood Pressure Targets

Background and Objectives@#This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP). @*Methods@#A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg). @*Results@#During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05–1.24) but not in those by the 2017 ACC/AHA definition. Elevated ontreatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18–1.70) and stroke (aHR, 1.19; 95% CI, 1.08–1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10;95% CI, 1.04–1.16). Similar results were seen in the propensity-score-matched cohort. @*Conclusion@#Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.

Pulsatile Hemodynamics and Coronary Artery Disease

Coronary artery disease (CAD) is the leading cause of human death and has a high prevalence throughout the world. Therefore, it is important to detect CAD early and to apply individualized therapy according to the patients' risk. There is an increasing interest in pulsatile arterial hemodynamics in the cardiovascular area. Widely used measurements of arterial pulsatile hemodynamics include pulse pressure, pulse wave velocity and augmentation index. Here, we will review underlying pathophysiology linking the association of arterial pulsatile hemodynamics with CAD, and the usefulness of the measurements of pulsatile hemodynamics in the prediction of future cardiovascular events of CAD patients.Clinical and therapeutic implications will be also addressed.

Deep Learning-Based Algorithm for the Detection and Characterization of MRI Safety of Cardiac Implantable Electronic Devices on Chest Radiographs

Objective@#With the recent development of various MRI-conditional cardiac implantable electronic devices (CIEDs), the accurate identification and characterization of CIEDs have become critical when performing MRI in patients with CIEDs. We aimed to develop and evaluate a deep learning-based algorithm (DLA) that performs the detection and characterization of parameters, including MRI safety, of CIEDs on chest radiograph (CR) in a single step and compare its performance with other related algorithms that were recently developed. @*Materials and Methods@#We developed a DLA (X-ray CIED identification [XCID]) using 9912 CRs of 958 patients with 968 CIEDs comprising 26 model groups from 4 manufacturers obtained between 2014 and 2019 from one hospital. The performance of XCID was tested with an external dataset consisting of 2122 CRs obtained from a different hospital and compared with the performance of two other related algorithms recently reported, including PacemakerID (PID) and Pacemaker identification with neural networks (PPMnn). @*Results@#The overall accuracies of XCID for the manufacturer classification, model group identification, and MRI safety characterization using the internal test dataset were 99.7% (992/995), 97.2% (967/995), and 98.9% (984/995), respectively. These were 95.8% (2033/2122), 85.4% (1813/2122), and 92.2% (1956/2122), respectively, with the external test dataset. In the comparative study, the accuracy for the manufacturer classification was 95.0% (152/160) for XCID and 91.3% for PPMnn (146/160), which was significantly higher than that for PID (80.0%,128/160; p < 0.001 for both). XCID demonstrated a higher accuracy (88.1%; 141/160) than PPMnn (80.0%; 128/160) in identifying model groups (p < 0.001). @*Conclusion@#The remarkable and consistent performance of XCID suggests its applicability for detection, manufacturer and model identification, as well as MRI safety characterization of CIED on CRs. Further studies are warranted to guarantee the safe use of XCID in clinical practice.

Factors Associated with Low Awareness of Heart Failure in the General Population of Korea

Background and Objectives@#Factors associated with low heart failure (HF) awareness have not been well-evaluated. This study was conducted to find out which demographic features would be associated with low HF awareness in the general population of Korea. @*Methods@#A telephone interview was conducted with 1,032 adults (58 years and 50.6% were male) across the country. Based on answer to 15 questions about HF, we scored from 0 to 15 points (mean, 7.53±2.75; median, 8; interquartile range, 6–9). A score of <8 was defined as low HF awareness, and a score of ≥8 was defined as high HF awareness. @*Results@#A total of 478 subjects (46.3%) had low HF awareness. HF awareness scores were 5.18±1.85 and 9.55±1.50 in subjects of low and high HF awareness groups, respectively. Subjects with low HF awareness were older, more female-dominant, more diabetic, lower educational and house hold income levels, and more frequently living in rural areas, compared to those with high HF awareness (p<0.05 for each). In multivariable logistic regression analyses, older age (≥67 years: odds ratio [OR], 1.61; 95% confidence interval [CI], 1.16–2.19; p=0.004), female sex (OR, 1.33; 95% CI, 1.02–1.73; p=0.034) and low educational level (high school graduate or less vs. college graduate: OR, 2.38; 95% CI, 1.75–3.22; p<0.001) were significantly associated with low HF awareness even after controlling for potential confounders. @*Conclusions@#Older age, female sex, and lower level of education were independently associated with low HF awareness in the general Korean population. More attention and education are needed for these vulnerable groups to improve HF awareness.

Gender differences in the presentation of chest pain in obstructive coronary artery disease: results from the Korean Women’s Chest Pain Registry

Background/Aims@#Chest pain in patients with obstructive coronary artery disease (OCAD) is affected by several social factors. The gender-based differences in chest pain among Koreans have yet to be investigated. @*Methods@#The study consecutively enrolled 1,549 patients (male/female, 514/1,035; 61 ± 11 years old) with suspected angina. The predictive factors for OCAD based on gender were evaluated. @*Results@#Men experienced more squeezing type pain on the left side of chest, while women demonstrated more dull quality pain in the retrosternal and epigastric area. After adjustment for risk factors, pain in the retrosternal area (odds ratio [OR], 1.491; 95% confidence interval [CI], 1.178 to 1.887) and aggravation by exercise (OR, 2.235; 95% CI, 1.745 to 2.861) were positively associated with OCAD. In men, shorter duration (OR, 1.581; 95% CI, 1.086 to 2.303) and dyspnea (OR, 1.610; 95% CI, 1.040 to 2.490) increased the probability for OCAD, while left-sided chest pain suggested a low probability for OCAD (OR, 0.590; 95% CI, 0.388 to 0.897). In women, aggravation by emotional stress (OR, 0.348; 95% CI, 0.162 to 0.746) and dizziness (OR, 0.457; 95% CI, 0.246 to 0.849) decreased the probability for OCAD. @*Conclusions@#This is the first study to focus on gender differences in chest pain among Koreans with angina. Symptoms with high probability for OCAD were different between sexes. Our findings suggest that patient’s medical history in pretest assessment for OCAD should be individualized considering gender.

The Prevention of Contrast Induced Nephropathy by Sarpogrelate: a Prospective Randomized Controlled Clinical Trial

BACKGROUND: Although some strategies are used for prophylaxis of contrast induced nephropathy, their efficacy is not fully established. Sarpogrelate can relieve vasospasm and have anti-inflammatory action. This study examined whether sarpogrelate reduces the incidence of contrast induced nephropathy (CIN) or subsequent renal impairment during four weeks after coronary angiography compared with a control group. METHODS: Seventy-four participants with chronic renal failure were randomly assigned to the sarpogrelate or control group. Patients assigned to the sarpogrelate group received oral saporogelate from 24 hours before contrast exposure up to one month after contrast exposure. The primary outcome of this study was the incidence of CIN within 48 hours after exposure to the contrast agent. RESULTS: Thirty-one subjects in the control group and 35 subjects in the sarpogrelate group were used for the analysis. Cumulative CIN occurred numerically more at 48 hours in the sarpogrelate group and less at one month without statistical significance (11.4% vs. 6.5% at 48 hours and 11.4% vs. 16.1% at one month, respectively). Baseline renal function was similar in both groups, but the estimated glomerular filtration rate (eGFR) was lower in the sarpogrelate group at 12 and 48 hours compared with the control group (45.6 vs. 54.7 mL/min/1.73m²; P = 0.023 and 39.9 vs. 50.6 mL/min/1.73m²; P = 0.020, respectively). At one month, the eGFR became comparable between the two groups because the eGFR was aggravated in the control group and maintained in the sarpogrelate group. CONCLUSION: This study failed to demonstrate that sarpogrelate has a renoprotective effect against contrast induced acute kidney injury. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01165567

Clinical Factors Associated with Obstructive Coronary Artery Disease in Patients with Out-of-Hospital Cardiac Arrest: Data from the Korean Cardiac Arrest Research Consortium (KoCARC) Registry

BACKGROUND: Although coronary artery disease (CAD) is a major cause of out-of-hospital cardiac arrest (OHCA), there has been no convinced data on the necessity of routine invasive coronary angiography (ICA) in OHCA. We investigated clinical factors associated with obstructive CAD in OHCA. METHODS: Data from 516 OHCA patients (mean age 58 years, 83% men) who underwent ICA after resuscitation was obtained from a nation-wide OHCA registry. Obstructive CAD was defined as the lesions with diameter stenosis ≥ 50% on ICA. Independent clinical predictors for obstructive CAD were evaluated using multiple logistic regression analysis, and their prediction performance was compared using area under the receiver operating characteristic curve with 10,000 repeated random permutations. RESULTS: Among study patients, 254 (49%) had obstructive CAD. Those with obstructive CAD were older (61 vs. 55 years, P < 0.001) and had higher prevalence of hypertension (54% vs. 36%, P < 0.001), diabetes mellitus (29% vs. 21%, P = 0.032), positive cardiac enzyme (84% vs. 74%, P = 0.010) and initial shockable rhythm (70% vs. 61%, P = 0.033). In multiple logistic regression analysis, old age (≥ 60 years) (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.36–3.00; P = 0.001), hypertension (OR, 1.74; 95% CI, 1.18–2.57; P = 0.005), positive cardiac enzyme (OR, 1.72; 95% CI, 1.09–2.70; P = 0.019), and initial shockable rhythm (OR, 1.71; 95% CI, 1.16–2.54; P = 0.007) were associated with obstructive CAD. Prediction ability for obstructive CAD increased proportionally when these 4 factors were sequentially combined (P < 0.001). CONCLUSION: In patients with OHCA, those with old age, hypertension, positive cardiac enzyme and initial shockable rhythm were associated with obstructive CAD. Early ICA should be considered in these patients.

Gender difference in the association between brachial-ankle pulse wave velocity and cardiovascular risk scores

BACKGROUND/AIMS@#Although brachial-ankle pulse wave velocity (baPWV) has been validated as a novel method to predict the cardiovascular risk in general population, the relevance of baPWV to the traditional risk scores has not been clearly revealed. This study investigated the relationship between baPWV and four different cardiovascular risk-predicting scores in men and women.@*METHODS@#A total of 539 subjects (58.1 ± 12.2 years, 50.1% men) without cardiovascular disease (CVD) who underwent health examinations including baPWV measurement were retrospectively analyzed. Four cardiovascular risk scores (Framingham risk score [FRS; 1998], Adult Treatment Panel [ATP] III revised FRS [2002], generalized FRS [2008], and American College of Cardiology/American Heart Association [ACC/AHA] CVD risk [2013]) were calculated in each subject.@*RESULTS@#In a total population, baPWV was moderately correlated with four cardiovascular risk scores (r = 0.577 for FRS; r = 0.594 for ATP III revised FRS; r = 0.589 for generalized FRS; r = 0.571 for ACC/AHA CVD risk; p < 0.001 for each). These correlations were stronger in women than in men (r = 0.649 vs. 0.451 for FRS; r = 0.719 vs. 0.411 for ATP III revised FRS; r = 0.735 vs. 0.540 for generalized FRS; r = 0.699 vs. 0.552 for ACC/AHA CVD risk; p for gender difference ≤ 0.005 for each).@*CONCLUSIONS@#In middle-aged and elderly Koreans without CVD, baPWV was identified as having a moderately positive correlation with four different risk scores. The correlation was stronger in women than in men, implying the better performance of baPWV in women for predicting cardiovascular risk of healthy population.

The Role of Transthoracic Echocardiography in Patients with Acute Ischemic Stroke: We Should Pay More Attention to Left Ventricular Ejection Fraction

No abstract available.

Findings of Single-Photon Emission Computed Tomography and Its Relation with Quantitative Coronary Angiography in Patients with Significant Stenosis of the Left Main Coronary Artery

OBJECTIVE: Unrecognized left main coronary artery disease (LMCD) is often fatal; however, accuracy of non-invasive tests for diagnosing LMCD is still unsatisfactory. This study was performed to elucidate single-photon emission computed tomography (SPECT) detection of LMCD using quantitative coronary angiography (QCA) data. MATERIALS AND METHODS: Fifty-five patients (39 men; mean age, 68.1 ± 10.9 years) diagnosed with significant left main (LM) stenosis (≥ 50%) by invasive coronary angiography (ICA) were retrospectively reviewed. All study patients underwent SPECT with pharmacologic stress within 30 days of ICA. All coronary lesions were quantified via QCA, and SPECT findings were compared with QCA results. RESULTS: Only four patients (7.3%) had isolated LMCD; all others had combined significant stenosis (≥ 70%) of one or more other epicardial coronary arteries. Patients with more severe coronary artery disease tended to have higher values for summed difference scores in a greater number of regions, but the specific pattern was not clearly defined. Summed stress score of SPECT did not differ according to LM stenosis severity. Only three patients (5.4%) had a typical LM pattern of reversible perfusion defect on SPECT. A significant negative linear correlation between stenosis severity and stress perfusion percent was found in the left anterior descending artery region (r = −0.455, p < 0.001) but not in the left circumflex artery. CONCLUSION: Single-photon emission computed tomography findings were heterogeneous, not specific and poorly correlated to QCA data in patients with significant LMCD. This may be due to highly prevalent significant stenosis of other epicardial coronary arteries.

Double Right Coronary Arteries Originated from Separate Ostia with Total Occlusive Lesion in One of the Two Right Coronary Arteries

Double right coronary arteries (RCA) are very rare congenital anomalies of coronary artery. We report a case of double RCA with total occlusion, incidentally found by collateral flows. A 71-year-old patient underwent percutaneous coronary intervention of left coronary arteries for angina, and the presence of double RCA was missed at initial coronary angiography (CAG). About 20 months later, second CAG was performed due to recurrent angina, and the CAG showed newly developed collateral flow suggesting the presence of the other missed RCA. There was a total occlusion at missed RCA and the lesion was successfully revascularized with drug eluting stent. If there was no collateral flow, the other RCA could not be found and its critical lesion could not be managed properly. Our case suggests that collateral flow can be a useful clue in detecting coronary anomaly. Besides, it is important to fully understand coronary anatomy, not to miss uncommon coronary lesion.

SEALONE (Safety and Efficacy of Coronary Computed Tomography Angiography with Low Dose in Patients Visiting Emergency Room) trial: study protocol for a randomized controlled trial

OBJECTIVE: Chest pain is one of the most common complaints in the emergency department (ED). Cardiac computed tomography angiography (CCTA) is a frequently used tool for the early triage of patients with low- to intermediate-risk acute chest pain. We present a study protocol for a multicenter prospective randomized controlled clinical trial testing the hypothesis that a low-dose CCTA protocol using prospective electrocardiogram (ECG)-triggering and limited-scan range can provide sufficient diagnostic safety for early triage of patients with acute chest pain. METHODS: The trial will include 681 younger adult (aged 20 to 55) patients visiting EDs of three academic hospitals for acute chest pain or equivalent symptoms who require further evaluation to rule out acute coronary syndrome. Participants will be randomly allocated to either low-dose or conventional CCTA protocol at a 2:1 ratio. The low-dose group will undergo CCTA with prospective ECG-triggering and restricted scan range from sub-carina to heart base. The conventional protocol group will undergo CCTA with retrospective ECG-gating covering the entire chest. Patient disposition is determined based on computed tomography findings and clinical progression and all patients are followed for a month. The primary objective is to prove that the chance of experiencing any hard event within 30 days after a negative low-dose CCTA is less than 1%. The secondary objectives are comparisons of the amount of radiation exposure, ED length of stay and overall cost. RESULTS AND CONCLUSION: Our low-dose protocol is readily applicable to current multi-detector computed tomography devices. If this study proves its safety and efficacy, dose-reduction without purchasing of expensive newer devices would be possible.

Huge Left Ventricular Thrombus and Apical Ballooning associated with Recurrent Massive Strokes in a Septic Shock Patient / 대한구급학회지

The most feared complication of left ventricular thrombus (LVT) is the occurrence of systemic thromboembolic events, especially in the brain. Herein, we report a patient with severe sepsis who suffered recurrent devastating embolic stroke. Transthoracic echocardiography revealed apical ballooning of the left ventricle with a huge LVT, which had not been observed in chest computed tomography before the stroke. This case emphasizes the importance of serial cardiac evaluation in patients with stroke and severe medical illness.

Re-mobilization of Lost Coronary Stent From the Axillary Artery to the Femoral Artery

Stent migration and loss are rare but can be devastating complications during percutaneous coronary intervention (PCI) for coronary artery disease. We report a unique case of wandering stent from the right coronary artery to the femoral artery via the axillary artery. Initially, the stent was stripped from the delivery catheter and embolized to axillary artery during emergent PCI. An intra-aortic balloon pump might have forced retrograde movement of the stent to axillary artery which have subsequently remobilized to the femoral artery. After stabilization, the stent was successfully removed by a percutaneous approach using a snare. Immediate retrieval of wandering stent is recommended for the prevention of secondary embolization.

Huge Left Ventricular Thrombus and Apical Ballooning associated with Recurrent Massive Strokes in a Septic Shock Patient / 대한중환자의학회지

The most feared complication of left ventricular thrombus (LVT) is the occurrence of systemic thromboembolic events, especially in the brain. Herein, we report a patient with severe sepsis who suffered recurrent devastating embolic stroke. Transthoracic echocardiography revealed apical ballooning of the left ventricle with a huge LVT, which had not been observed in chest computed tomography before the stroke. This case emphasizes the importance of serial cardiac evaluation in patients with stroke and severe medical illness.