2014 Vol. 11, No. 1
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2014, 11(1): 1-12.
doi: 10.3969/j.issn.1671-5411.2014.01.002
Abstract:
Background Acute myocardial infarction (AMI) is a common cause of heart failure (HF), which can develop soon after AMI and may persist or resolve or develop late. HF after an MI is a major source of mortality. The cumulative incidence, prevalence and resolution of HF after MI in different age groups are poorly described. This study describes the natural history of HF after AMI according to age. Methods Patients with AMI during 1998 were identified from hospital records. HF was defined as treatment of symptoms and signs of HF with loop diuretics and was considered to have resolved if loop diuretic therapy could be stopped without recurrence of symptoms. Patients were categorised into those aged 75 years. Results Of 896 patients, 311, 297 and 288 were aged 75 years and of whom 24%, 57% and 82% had died respectively by December 2005. Of these deaths, 24 (8%), 68 (23%) and 107 (37%) occurred during the index admission, many associated with acute HF. A further 37 (12%), 63 (21%) and 82 (29%) developed HF that persisted until discharge, of whom 15, 44 and 62 subsequently died. After discharge, 53 (24%), 55 (40%) and 37 (47%) patients developed HF for the first time, of whom 26%, 62% and 76% subsequently died. Death was preceded by the development of HF in 35 (70%), 93 (91%) and 107 (85%) in aged 75 years, respectively. Conclusions The risk of developing HF and of dying after an MI increases progressively with age. Regardless of age, most deaths after a MI are preceded by the development of HF.
Background Acute myocardial infarction (AMI) is a common cause of heart failure (HF), which can develop soon after AMI and may persist or resolve or develop late. HF after an MI is a major source of mortality. The cumulative incidence, prevalence and resolution of HF after MI in different age groups are poorly described. This study describes the natural history of HF after AMI according to age. Methods Patients with AMI during 1998 were identified from hospital records. HF was defined as treatment of symptoms and signs of HF with loop diuretics and was considered to have resolved if loop diuretic therapy could be stopped without recurrence of symptoms. Patients were categorised into those aged 75 years. Results Of 896 patients, 311, 297 and 288 were aged 75 years and of whom 24%, 57% and 82% had died respectively by December 2005. Of these deaths, 24 (8%), 68 (23%) and 107 (37%) occurred during the index admission, many associated with acute HF. A further 37 (12%), 63 (21%) and 82 (29%) developed HF that persisted until discharge, of whom 15, 44 and 62 subsequently died. After discharge, 53 (24%), 55 (40%) and 37 (47%) patients developed HF for the first time, of whom 26%, 62% and 76% subsequently died. Death was preceded by the development of HF in 35 (70%), 93 (91%) and 107 (85%) in aged 75 years, respectively. Conclusions The risk of developing HF and of dying after an MI increases progressively with age. Regardless of age, most deaths after a MI are preceded by the development of HF.
2014, 11(1): 13-19.
doi: 10.3969/j.issn.1671-5411.2014.01.008
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Background Circulating microparticles (MPs) have been reported to be associated with coronary artery disease (CAD). In this study, we explored the relationship between MPs procoagulant activity and characteristics of atherosclerotic plaque detected by 64-slice computed tomography angiography (CTA). Methods In 127 consecutive patients with CAD but without acute coronary syndrome and who underwent 64-slice CTA, MPs procoagulant activity in plasma (by a thrombin generation test), soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and N(epsilon)-(carboxymethyl) lysine (CML) circulating levels (by ELISA) were measured. A quantitative volumetric analysis of the lumen and plaque burden of the vessel wall (soft and calcific components), for the three major coronary vessels, was performed. The patients were classified in three groups according to the presence of calcium volume: non-calcified plaque (NCP) group (calcium volume (%) = 0), moderate calcified plaque (MCP) group (0 Results MPs procoagulant activity and CML levels were higher in MCP group than in CP or NCP group (P = 0.009 and P = 0.027, respectively). MPs procoagulant activity was positively associated with CML (r = 0.317, P r = 0.216, P = 0.0025). Conclusions MPs procoagulant activity was higher in the MCP patient group and correlated positively with sLOX-1 and CML levels, suggesting that it may characterize a state of blood vulnerability that may locally precipitate plaque instability and increase the risk of subsequent major cardiovascular events.
Background Circulating microparticles (MPs) have been reported to be associated with coronary artery disease (CAD). In this study, we explored the relationship between MPs procoagulant activity and characteristics of atherosclerotic plaque detected by 64-slice computed tomography angiography (CTA). Methods In 127 consecutive patients with CAD but without acute coronary syndrome and who underwent 64-slice CTA, MPs procoagulant activity in plasma (by a thrombin generation test), soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and N(epsilon)-(carboxymethyl) lysine (CML) circulating levels (by ELISA) were measured. A quantitative volumetric analysis of the lumen and plaque burden of the vessel wall (soft and calcific components), for the three major coronary vessels, was performed. The patients were classified in three groups according to the presence of calcium volume: non-calcified plaque (NCP) group (calcium volume (%) = 0), moderate calcified plaque (MCP) group (0 Results MPs procoagulant activity and CML levels were higher in MCP group than in CP or NCP group (P = 0.009 and P = 0.027, respectively). MPs procoagulant activity was positively associated with CML (r = 0.317, P r = 0.216, P = 0.0025). Conclusions MPs procoagulant activity was higher in the MCP patient group and correlated positively with sLOX-1 and CML levels, suggesting that it may characterize a state of blood vulnerability that may locally precipitate plaque instability and increase the risk of subsequent major cardiovascular events.
2014, 11(1): 20-25.
doi: 10.3969/j.issn.1671-5411.2014.01.005
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Objectives To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. Methods The Medline databases were searched using the OvidSP platforms with the search strategy: “QT interval” or “QT” and “age” or “aging”. The entry criteria were: over 10,000 apparently healthy individuals with data on both sexes; QT interval corrected for heart rate (QTc) and an expression of its variance for multiple age decades extending into the older ages. Results QTc increased in duration with increasing age. Considering a modest one SD increment in QTc in the normal population, the addition of Chlorpromazine produced a QTc on average greater than 450 ms for ages 70 years and older. Risperidone, that did not on average alter QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70 years under some circumstances. QTc prolongation > 500 ms with antipsychotic drugs is more likely for persons with QTc initially at the 99th percentile. It may occur with Haloperidol which does not on average alter QTc. Conclusions The range of values for the QT interval in apparently normal older men or women, when combined with the range of expected QT interval changes induced by antipsychotic drugs, can readily be associated with prolonged QTc. Individuals with QTc at the 99th percentile may have serious QTc prolongation with antipsychotic drugs even those that are not usually associated with QTc prolongation.
Objectives To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. Methods The Medline databases were searched using the OvidSP platforms with the search strategy: “QT interval” or “QT” and “age” or “aging”. The entry criteria were: over 10,000 apparently healthy individuals with data on both sexes; QT interval corrected for heart rate (QTc) and an expression of its variance for multiple age decades extending into the older ages. Results QTc increased in duration with increasing age. Considering a modest one SD increment in QTc in the normal population, the addition of Chlorpromazine produced a QTc on average greater than 450 ms for ages 70 years and older. Risperidone, that did not on average alter QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70 years under some circumstances. QTc prolongation > 500 ms with antipsychotic drugs is more likely for persons with QTc initially at the 99th percentile. It may occur with Haloperidol which does not on average alter QTc. Conclusions The range of values for the QT interval in apparently normal older men or women, when combined with the range of expected QT interval changes induced by antipsychotic drugs, can readily be associated with prolonged QTc. Individuals with QTc at the 99th percentile may have serious QTc prolongation with antipsychotic drugs even those that are not usually associated with QTc prolongation.
2014, 11(1): 26-31.
doi: 10.3969/j.issn.1671-5411.2014.01.010
Abstract:
Objectives To investigate the procedure characteristics and long term follow-up of percutaneous coronary intervention (PCI) for saphaneous vein graft (SVG) lesions in the elderly patients. Methods From December 2005 to December 2011, 84 graft lesions were treated percutaneously. Seventeen were located at proximal anastomosis, 48 were located at SVG body, 19 were located at distal anastomosis. Primary endpoint was defined as major adverse cardiovascular events (MACE, composite of cardiac death, target vessel revascularization, acute myocardial infarction). Results The graft age was 6.7 ± 4.0 years. Most anastomosis lesions (80.0%) presented within one year post coronary artery bypass grafting (CABG). Proximal anastomosis lesion had the lowest successful rate for PCI compared with graft body and distal anastomosis lesions (70.6% vs. 91.7%, 79.0%, P P P P vs. body graft PCI 16.7%, distal anastomosis PCI 21.1%; P P = 0.04). Conclusions PCI of SVG lesions is feasible with lower success rate. PCI of ostial graft anastomosis lesions had the lowest procedure success rate and highest MACE rate compared with graft body and distal anastomosis lesions. Old myocardial infarction was a predictive factor of poor outcomes.
Objectives To investigate the procedure characteristics and long term follow-up of percutaneous coronary intervention (PCI) for saphaneous vein graft (SVG) lesions in the elderly patients. Methods From December 2005 to December 2011, 84 graft lesions were treated percutaneously. Seventeen were located at proximal anastomosis, 48 were located at SVG body, 19 were located at distal anastomosis. Primary endpoint was defined as major adverse cardiovascular events (MACE, composite of cardiac death, target vessel revascularization, acute myocardial infarction). Results The graft age was 6.7 ± 4.0 years. Most anastomosis lesions (80.0%) presented within one year post coronary artery bypass grafting (CABG). Proximal anastomosis lesion had the lowest successful rate for PCI compared with graft body and distal anastomosis lesions (70.6% vs. 91.7%, 79.0%, P P P P vs. body graft PCI 16.7%, distal anastomosis PCI 21.1%; P P = 0.04). Conclusions PCI of SVG lesions is feasible with lower success rate. PCI of ostial graft anastomosis lesions had the lowest procedure success rate and highest MACE rate compared with graft body and distal anastomosis lesions. Old myocardial infarction was a predictive factor of poor outcomes.
2014, 11(1): 32-38.
doi: 10.3969/j.issn.1671-5411.2014.01.007
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Background Arterial stiffness and homocysteine are both powerful predictors of cardiovascular disease, especially in older populations. Previous studies have investigated the association of homocysteine with arterial stiffness in human subjects, while the relationship between homocysteine and arterial stiffness in the elderly is still indefinite. The current study examined the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. Methods We related serum levels of homocysteine to two measures of arterial stiffness (carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV) in 780 participants (46.3% men, mean age 71.9 years (ranging 65–96 years old)) from two communities of Beijing, China. Arterial stiffness was measured within two days of the time of biomarker measurement. Results In multiple-adjusted models, homocysteine levels was strongly associated with the carotid-femoral PWV (standardized β = 0.13, P Conclusions In Chinese elderly persons, serum homocysteine levels are associated with alterations of aortic stiffness.
Background Arterial stiffness and homocysteine are both powerful predictors of cardiovascular disease, especially in older populations. Previous studies have investigated the association of homocysteine with arterial stiffness in human subjects, while the relationship between homocysteine and arterial stiffness in the elderly is still indefinite. The current study examined the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. Methods We related serum levels of homocysteine to two measures of arterial stiffness (carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV) in 780 participants (46.3% men, mean age 71.9 years (ranging 65–96 years old)) from two communities of Beijing, China. Arterial stiffness was measured within two days of the time of biomarker measurement. Results In multiple-adjusted models, homocysteine levels was strongly associated with the carotid-femoral PWV (standardized β = 0.13, P Conclusions In Chinese elderly persons, serum homocysteine levels are associated with alterations of aortic stiffness.
2014, 11(1): 39-43.
doi: 10.3969/j.issn.1671-5411.2014.01.011
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Background In order to acquire a high quality image with a low radiation dose, prospective electrocardiogram (ECG)-triggered computed tomography coronary angiography (CTCA) requires a stable heart rate (HR) Methods From March 2013 to June 2013, 313 patients underwent prospective ECG-triggered CTCA. Two hundred and thirty two of them received esmolol before angiography. We retrospectively analyzed clinical characteristics, esmolol dose, radiation exposure dose, and the change in HR and blood pressure in these 232 patients. Results A total of 232 patients with a HR > 65 beats/min before CTCA examination received intravenous esmolol treatment (mean dose of 57.26 ± 15.39 mg). The mean initial HR (HR1), slowest HR (HR2), and the HR 30 min after HR2 (HR3) were 75.06 ± 5.59, 60.75 ± 4.00, and 75.54 ± 5.96 beats/min, respectively (HR1 vs. HR2, P vs. HR3, P Conclusions HR could be rapidly controlled at an optimum level with intravenous esmolol before prospective ECG-triggered high-pitch spiral acquisition for CTCA. Consequently, the patients received a very low radiation dose.
Background In order to acquire a high quality image with a low radiation dose, prospective electrocardiogram (ECG)-triggered computed tomography coronary angiography (CTCA) requires a stable heart rate (HR) Methods From March 2013 to June 2013, 313 patients underwent prospective ECG-triggered CTCA. Two hundred and thirty two of them received esmolol before angiography. We retrospectively analyzed clinical characteristics, esmolol dose, radiation exposure dose, and the change in HR and blood pressure in these 232 patients. Results A total of 232 patients with a HR > 65 beats/min before CTCA examination received intravenous esmolol treatment (mean dose of 57.26 ± 15.39 mg). The mean initial HR (HR1), slowest HR (HR2), and the HR 30 min after HR2 (HR3) were 75.06 ± 5.59, 60.75 ± 4.00, and 75.54 ± 5.96 beats/min, respectively (HR1 vs. HR2, P vs. HR3, P Conclusions HR could be rapidly controlled at an optimum level with intravenous esmolol before prospective ECG-triggered high-pitch spiral acquisition for CTCA. Consequently, the patients received a very low radiation dose.
2014, 11(1): 44-49.
doi: 10.3969/j.issn.1671-5411.2014.01.011
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Background Severely calcified coronary lesions respond poorly to balloon angioplasty, resulting in incomplete and asymmetrical stent expansion. Therefore, adequate plaque modification prior to drug-eluting stent (DES) implantation is the key for calcified lesion treatment. This study was to evaluate the safety and efficacy of cutting balloon angioplasty for severely calcified coronary lesions. Methods Ninety-two consecutive patients with severely calcified lesions (defined as calcium arc ≥ 180° calcium length ratio ≥ 0.5) treated with balloon dilatation before DES implantation were randomly divided into two groups based on the balloon type: 45 patients in the conventional balloon angioplasty (BA) group and 47 patients in the cutting balloon angioplasty (CB) group. Seven cases in BA group did not satisfactorily achieve dilatation and were transferred into the CB group. Intravascular ultrasound (IVUS) was performed before balloon dilatation and after stent implantation to obtain qualitative and quantitative lesion characteristics and evaluate the stent, including minimum lumen cross-sectional area (CSA), calcified arc and length, minimum stent CSA, stent apposition, stent symmetry, stent expansion, vessel dissection, and branch vessel jail. In-hospital, 1-month, and 6-month major adverse cardiac events (MACE) were reported. Results There were no statistical differences in clinical characteristics between the two groups, including calcium arc (222.2° ± 22.2°vs. 235.0° ± 22.1°, P = 0.570), calcium length ratio (0.67 ± 0.06 vs. 0.77 ± 0.05, P = 0.130), and minimum lumen CSA before PCI (2.59 ± 0.08 mm2 vs. 2.52 ± 0.08 mm2, P = 0.550). After stent implantation, the final minimum stent CSA (6.26 ± 0.40 mm2 vs. 5.03 ± 0.33 mm2; P = 0.031) and acute lumen gain (3.74 ± 0.38 mm2 vs. 2.44 ± 0.29 mm2, P = 0.015) were significantly larger in the CB group than that of the BA group. There were not statistically differences in stent expansion, stent symmetry, incomplete stent apposition, vessel dissection and branch vessel jail between two groups. The 30-day and 6-month MACE rates were also not different. Conclusions Cutting balloon angioplasty before DES implantation in severely calcified lesions appears to be more efficacies including significantly larger final stent CSA and larger acute lumen gain, without increasing complications during operations and the MACE rate in 6-month.
Background Severely calcified coronary lesions respond poorly to balloon angioplasty, resulting in incomplete and asymmetrical stent expansion. Therefore, adequate plaque modification prior to drug-eluting stent (DES) implantation is the key for calcified lesion treatment. This study was to evaluate the safety and efficacy of cutting balloon angioplasty for severely calcified coronary lesions. Methods Ninety-two consecutive patients with severely calcified lesions (defined as calcium arc ≥ 180° calcium length ratio ≥ 0.5) treated with balloon dilatation before DES implantation were randomly divided into two groups based on the balloon type: 45 patients in the conventional balloon angioplasty (BA) group and 47 patients in the cutting balloon angioplasty (CB) group. Seven cases in BA group did not satisfactorily achieve dilatation and were transferred into the CB group. Intravascular ultrasound (IVUS) was performed before balloon dilatation and after stent implantation to obtain qualitative and quantitative lesion characteristics and evaluate the stent, including minimum lumen cross-sectional area (CSA), calcified arc and length, minimum stent CSA, stent apposition, stent symmetry, stent expansion, vessel dissection, and branch vessel jail. In-hospital, 1-month, and 6-month major adverse cardiac events (MACE) were reported. Results There were no statistical differences in clinical characteristics between the two groups, including calcium arc (222.2° ± 22.2°vs. 235.0° ± 22.1°, P = 0.570), calcium length ratio (0.67 ± 0.06 vs. 0.77 ± 0.05, P = 0.130), and minimum lumen CSA before PCI (2.59 ± 0.08 mm2 vs. 2.52 ± 0.08 mm2, P = 0.550). After stent implantation, the final minimum stent CSA (6.26 ± 0.40 mm2 vs. 5.03 ± 0.33 mm2; P = 0.031) and acute lumen gain (3.74 ± 0.38 mm2 vs. 2.44 ± 0.29 mm2, P = 0.015) were significantly larger in the CB group than that of the BA group. There were not statistically differences in stent expansion, stent symmetry, incomplete stent apposition, vessel dissection and branch vessel jail between two groups. The 30-day and 6-month MACE rates were also not different. Conclusions Cutting balloon angioplasty before DES implantation in severely calcified lesions appears to be more efficacies including significantly larger final stent CSA and larger acute lumen gain, without increasing complications during operations and the MACE rate in 6-month.
2014, 11(1): 50-56.
doi: 10.3969/j.issn.1671-5411.2014.01.004
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Objective Brain natriuretic peptide (BNP) is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects (CHF). BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients (BNP > 3000 ng/L) with 10 matched, healthy controls. Methods Cutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating (+44°C, 10 min) was used to evoke a maximum local dilator response. Results Non-invasive iontophoretic administration of either BNP or acetylcholine (ACh), a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine-methyl-ester (L-NAME), blocked the BNP response (in controls). Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls (increase in flow: 251% in CHF vs. 908% in controls; P Conclusions The findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulation in CHF.
Objective Brain natriuretic peptide (BNP) is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects (CHF). BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients (BNP > 3000 ng/L) with 10 matched, healthy controls. Methods Cutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating (+44°C, 10 min) was used to evoke a maximum local dilator response. Results Non-invasive iontophoretic administration of either BNP or acetylcholine (ACh), a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine-methyl-ester (L-NAME), blocked the BNP response (in controls). Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls (increase in flow: 251% in CHF vs. 908% in controls; P Conclusions The findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulation in CHF.
2014, 11(1): 57-62.
doi: 10.3969/j.issn.1671-5411.2014.01.003
Abstract:
Objective To investigate the relationship between serum FFAs levels and the severity of coronary artery lesions in elderly patients with coronary heart disease (CAD). Methods A total of 172 elderly patients who underwent coronary angiography were divided into CAD group (n = 128) and non-CAD group (n = 44) according to the results of coronary angiography. Serum FFAs and lipid levels were measured and the Gensini score were calculated. Results No matter the differences between age, gender and the usage of statins or not, there was no statistical significance in FFAs levels (P > 0.05). In terms of the Gensini score, it was higher in patients aged 70–79 years than in patients 60–69 years old [15.00 (5.00, 34.00) vs. 10.00 (2.00, 24.00), P vs. 7.00 (2.50, 19.75), P vs. 6.50 (2.00, 18.00), P vs. 388.00 (258.50, 495.25) mEq/L, P vs. 1.00 (0, 5.00), P P > 0.05). Furthermore, the FFAs levels were positively correlated with the Gensini score (r = 0.394, P = 0.005). Regression analysis showed that the FFAs levels were related to the Gensini score independently after adjusting for the other risk factors. Conclusions The serum FFAs levels were associated with the Gensini score in elderly patients with CAD. It might indicate FFAs as a biomarker predicting the severity of coronary artery lesions.
Objective To investigate the relationship between serum FFAs levels and the severity of coronary artery lesions in elderly patients with coronary heart disease (CAD). Methods A total of 172 elderly patients who underwent coronary angiography were divided into CAD group (n = 128) and non-CAD group (n = 44) according to the results of coronary angiography. Serum FFAs and lipid levels were measured and the Gensini score were calculated. Results No matter the differences between age, gender and the usage of statins or not, there was no statistical significance in FFAs levels (P > 0.05). In terms of the Gensini score, it was higher in patients aged 70–79 years than in patients 60–69 years old [15.00 (5.00, 34.00) vs. 10.00 (2.00, 24.00), P vs. 7.00 (2.50, 19.75), P vs. 6.50 (2.00, 18.00), P vs. 388.00 (258.50, 495.25) mEq/L, P vs. 1.00 (0, 5.00), P P > 0.05). Furthermore, the FFAs levels were positively correlated with the Gensini score (r = 0.394, P = 0.005). Regression analysis showed that the FFAs levels were related to the Gensini score independently after adjusting for the other risk factors. Conclusions The serum FFAs levels were associated with the Gensini score in elderly patients with CAD. It might indicate FFAs as a biomarker predicting the severity of coronary artery lesions.
2014, 11(1): 63-73.
doi: 10.3969/j.issn.1671-5411.2014.01.001
Abstract:
Background Ciliopathies are a group of diseases associated with abnormal structure or function of primary cilia. Ciliopathies include polycystic kidney disease (PKD), a pathology associated with vascular hypertension. We previously showed that cilia length regulates cilia function, and cilia function is required for nitric oxide (NO) biosynthesis in endothelial cells. Because patients with PKD show abnormal sensory cilia function, the aim of our current study was to search for a targeted therapy focused on primary cilia, which we refer to as ‘ciliotherapy’. Methods and Results In the present studies, our in vitro analyses refined fenoldopam as an equipotent and more specific dopaminergic agonist to regulate cilia length and function. Our in vitro studies indicated that fenoldopam increased cilia length and serum NO thereby reducing blood pressure in a PKD mouse model. Our crossover, multicenter, double-blind and placebo-controlled clinical study further indicated that cilia-targeting therapy showed an overall reduction in mean arterial pressure in PKD patients. Conclusions Overall, our studies provide the first evidence of ciliotherapy as an innovative intervention in patients with abnormal primary cilia.
Background Ciliopathies are a group of diseases associated with abnormal structure or function of primary cilia. Ciliopathies include polycystic kidney disease (PKD), a pathology associated with vascular hypertension. We previously showed that cilia length regulates cilia function, and cilia function is required for nitric oxide (NO) biosynthesis in endothelial cells. Because patients with PKD show abnormal sensory cilia function, the aim of our current study was to search for a targeted therapy focused on primary cilia, which we refer to as ‘ciliotherapy’. Methods and Results In the present studies, our in vitro analyses refined fenoldopam as an equipotent and more specific dopaminergic agonist to regulate cilia length and function. Our in vitro studies indicated that fenoldopam increased cilia length and serum NO thereby reducing blood pressure in a PKD mouse model. Our crossover, multicenter, double-blind and placebo-controlled clinical study further indicated that cilia-targeting therapy showed an overall reduction in mean arterial pressure in PKD patients. Conclusions Overall, our studies provide the first evidence of ciliotherapy as an innovative intervention in patients with abnormal primary cilia.
2014, 11(1): 74-78.
doi: 10.3969/j.issn.1671-5411.2014.01.013
Abstract:
Background Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocysteine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the formation of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr–/–) mice. Methods Forty-eight 7-week-old LDLr–/– mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed. Results At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P P Conclusions Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLr–/– mice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.
Background Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocysteine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the formation of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr–/–) mice. Methods Forty-eight 7-week-old LDLr–/– mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed. Results At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P P Conclusions Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLr–/– mice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.
2014, 11(1): 79-82.
doi: 10.3969/j.issn.1671-5411.2014.01.014
Abstract:
Background Heart failure (HF) is a common disease with complex pathophysiological causes. The diagnosis of HF commonly relies on comprehensive analyses of medical history and symptoms, and results from echocardiography and biochemical tests. Galectin-3, a relatively new biomarker in HF, was approved by the US Food and Drug Administration in 2010 as a marker in the stratification of risk for HF. We assessed galectin-3 as a biomarker for HF diagnosis in patients with preserved ejection fraction (pEF) and compared its performance with that of B-type natriuretic peptide (BNP). Methods Thirty-five pEF patients with HF (HFpEF group) and 43 pEF patients without HF (control group) were enrolled. Plasma levels of galectin-3 and BNP in HFpEF and control subjects were determined. Sensitivity, specificity, predictive values, and accuracy of galectin-3 and BNP as markers for HF diagnosis were calculated and compared. Results Levels of galectin-3 and BNP were 23.09 ± 6.97 ng/mL and 270.46 ± 330.41 pg/mL in the HFpEF group, and 16.74 ± 2.75 ng/mL and 59.94 ± 29.93 pg/mL in the control group, respectively. Differences in levels of galectin-3 and BNP between the two groups were significant (P P P P > 0.05). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.891 (0.808–0.974) and 0.896 (0.809–0.984) for galectin-3 and BNP, respectively, with no significant difference between the two values (P > 0.05). Conclusions The level of galectin-3 is significantly elevated in patients with HF. Galectin-3 and BNP are useful biomarkers for the diagnosis of HF in patients with pEF.
Background Heart failure (HF) is a common disease with complex pathophysiological causes. The diagnosis of HF commonly relies on comprehensive analyses of medical history and symptoms, and results from echocardiography and biochemical tests. Galectin-3, a relatively new biomarker in HF, was approved by the US Food and Drug Administration in 2010 as a marker in the stratification of risk for HF. We assessed galectin-3 as a biomarker for HF diagnosis in patients with preserved ejection fraction (pEF) and compared its performance with that of B-type natriuretic peptide (BNP). Methods Thirty-five pEF patients with HF (HFpEF group) and 43 pEF patients without HF (control group) were enrolled. Plasma levels of galectin-3 and BNP in HFpEF and control subjects were determined. Sensitivity, specificity, predictive values, and accuracy of galectin-3 and BNP as markers for HF diagnosis were calculated and compared. Results Levels of galectin-3 and BNP were 23.09 ± 6.97 ng/mL and 270.46 ± 330.41 pg/mL in the HFpEF group, and 16.74 ± 2.75 ng/mL and 59.94 ± 29.93 pg/mL in the control group, respectively. Differences in levels of galectin-3 and BNP between the two groups were significant (P P P P > 0.05). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.891 (0.808–0.974) and 0.896 (0.809–0.984) for galectin-3 and BNP, respectively, with no significant difference between the two values (P > 0.05). Conclusions The level of galectin-3 is significantly elevated in patients with HF. Galectin-3 and BNP are useful biomarkers for the diagnosis of HF in patients with pEF.
2014, 11(1): 83-89.
doi: 10.3969/j.issn.1671-5411.2014.01.009
Abstract:
Several studies have shown that coronary artery bypass surgery (CABG) is superior to percutaneous coronary intervention (PCI) in patients with diabetes and multi-vessel disease. Whether this advantage of CABG over PCI is confined to diabetics who require insulin is unknown. We review the published literature comparing CABG with PCI in diabetics including 8 cohorts and 4,786 patients. There was a lower rate for all-cause mortality (Relative risk (RR): 0.78, 95% confidence interval (CI): 0.62–0.99), and for major adverse cardiac and cerebrovascular events (MACCE, RR: 0.59, 95% CI: 0.47–0.75) for CABG compared to PCI. Composite outcome of mortality, myocardial infarction and stoke was similar between CABG and PCI (RR: 0.87, 95% CI: 0.54–1.42). Visual inspection of the forest plots showed that in most analyses, the point estimates of the RR are similar between the insulin requiring group and non-insulin requiring group. On meta-regression, there was no interaction between status of insulin requirement and revascularization strategies (P > 0.05 for all). The presented data on the still unpublished analysis of the FREEDOM trial showed similar results. Thus, in the current era, CABG is superior to PCI with lower mortality and MACCE rates, but the state of insulin requirement had no effect on the outcomes from the two revascularization strategies.
Several studies have shown that coronary artery bypass surgery (CABG) is superior to percutaneous coronary intervention (PCI) in patients with diabetes and multi-vessel disease. Whether this advantage of CABG over PCI is confined to diabetics who require insulin is unknown. We review the published literature comparing CABG with PCI in diabetics including 8 cohorts and 4,786 patients. There was a lower rate for all-cause mortality (Relative risk (RR): 0.78, 95% confidence interval (CI): 0.62–0.99), and for major adverse cardiac and cerebrovascular events (MACCE, RR: 0.59, 95% CI: 0.47–0.75) for CABG compared to PCI. Composite outcome of mortality, myocardial infarction and stoke was similar between CABG and PCI (RR: 0.87, 95% CI: 0.54–1.42). Visual inspection of the forest plots showed that in most analyses, the point estimates of the RR are similar between the insulin requiring group and non-insulin requiring group. On meta-regression, there was no interaction between status of insulin requirement and revascularization strategies (P > 0.05 for all). The presented data on the still unpublished analysis of the FREEDOM trial showed similar results. Thus, in the current era, CABG is superior to PCI with lower mortality and MACCE rates, but the state of insulin requirement had no effect on the outcomes from the two revascularization strategies.
2014, 11(1): 90-92.
doi: 10.3969/j.issn.1671-5411.2014.01.006
Abstract:
In this case report, we present the occlusion of multiple coronary artery fistulae originating from proximal left anterior descending (LAD) and right sinus valsavla and empting to the pulmonary artery at the same place. We occluded LAD fistulae by using thrombus aspiration catheter as a delivery guide. To the best of our knowlege, this is the first case of occlusion of coronary fistulae with the help of thrombus aspiration catheter. Our experience may suggest that thrombus aspiration catheters can be used in treating coronary artery fistulae with difficult anotomy.
In this case report, we present the occlusion of multiple coronary artery fistulae originating from proximal left anterior descending (LAD) and right sinus valsavla and empting to the pulmonary artery at the same place. We occluded LAD fistulae by using thrombus aspiration catheter as a delivery guide. To the best of our knowlege, this is the first case of occlusion of coronary fistulae with the help of thrombus aspiration catheter. Our experience may suggest that thrombus aspiration catheters can be used in treating coronary artery fistulae with difficult anotomy.
