Krishnaraj Rathod | Queen Mary, University of London (original) (raw)

Papers by Krishnaraj Rathod

Journal of the American College of Cardiology, Jan 23, 2018

A large proportion of patients presenting with non-ST-segment elevation myocardial infarction (NS... more A large proportion of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) present with multivessel disease (MVD). There is uncertainty in the role of complete coronary revascularization in this group of patients. The aim of this study was to investigate the outcomes of complete revascularization compared with culprit vessel-only intervention in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI) for NSTEMI. The authors undertook an observational cohort study of 37,491 NSTEMI patients treated between 2005 and 2015 at the 8 heart attack centers in London. Clinical details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society (BCIS) PCI dataset. A total of 21,857 patients (58.3%) presented with NSTEMI and MVD. Primary outcome was all-cause mortality at a median follow-up of 4.1 years (interquartile range: 2.2 to 5.8 years). A total of 11,737 (53.7%) patients und...

Journal of the American College of Cardiology

Journal of the American College of Cardiology

Journal of cardiovascular pharmacology and therapeutics, Jan 6, 2018

In the follow-up of patients in a trial of intracoronary sodium nitrite given during primary perc... more In the follow-up of patients in a trial of intracoronary sodium nitrite given during primary percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI), we found a reduction in the incidence of major adverse cardiac events (MACEs). Specifically, MACE rates were 5.2% versus 25.0% with placebo at 3 years ( P = .013). Such MACE reductions should also be associated with economic benefit. Thus, we assessed the cost utility of sodium nitrite therapy versus standard primary PCI only. We developed a model to simulate costs and quality-adjusted life years (QALYs) over the first 36 months after ST-Segment Elevation Myocardial Infarction (STEMI). Decision tree analysis was used to assess different potential cardiovascular outcomes after STEMI for patients in both treatment groups. Model inputs were derived from the NITRITE-AMI study. Cost of comparative treatments and follow-up in relation to cardiovascular events was calculated from the United Kingdom National Health Ser...

Heart and vessels, Jan 27, 2018

Transradial access is increasingly used for coronary angiography and percutaneous coronary interv... more Transradial access is increasingly used for coronary angiography and percutaneous coronary intervention, however, femoral access remains necessary for numerous procedures, including complex high-risk interventions, structural procedures, and procedures involving mechanical circulatory support. Optimising the safety of this approach is crucial to minimize costly and potentially life-threatening complications. We initiated a quality improvement project recommending routine fluoroscopic guidance (femoral head), and upfront femoral angiography should be performed to assess for location and immediate complications. We assessed the effect of these measures on the rate of vascular complications. Data were collected prospectively on 4534 consecutive patients undergoing femoral coronary angiographic procedures from 2015 to 2017. The primary end-point was any access complication. Outcomes were compared pre and post introduction including the use of an Interrupted Time-Series (ITS) analysis. 1...

Free radical biology & medicine, Jan 20, 2018

Oral reduction of nitrate to nitrite is dependent on the oral microbiome and is the first step of... more Oral reduction of nitrate to nitrite is dependent on the oral microbiome and is the first step of an alternative mammalian pathway to produce nitric oxide in humans. Preliminary evidence suggests important sex differences in this pathway. We prospectively investigated sex-differences following inorganic nitrate supplementation on nitrate/nitrite levels and vascular function, and separately examined sex differences in oral nitrate reduction, and oral microbiota by 16S rRNA profiling. At baseline, females exhibit higher nitrite levels in all biological matrices despite similar nitrate levels to males. Following inorganic nitrate supplementation, plasma nitrite was increased to a significantly greater extent in females than in males and pulse wave velocity was only reduced in females. Females exhibited higher oral bacterial nitrate-reducing activity at baseline and after nitrate supplementation. Despite these differences, there were no differences in the composition of either the total...

International journal of cardiology, Sep 1, 2018

Pre-clinical evidence suggests delivery of nitric oxide (NO) through administration of inorganic ... more Pre-clinical evidence suggests delivery of nitric oxide (NO) through administration of inorganic nitrite suppresses arrhythmias resulting from acute ischaemia and reperfusion (I/R). To date no assessment of whether inorganic nitrite might limit reperfusion arrhythmia has occurred in man, therefore we explored the effects on I/R-induced ventricular arrhythmias in the NITRITE-AMI cohort. In the NITRITE-AMI cohort, Holter analysis was performed prior to and for 24 h after primary PCI in 80 patients who received either intra-coronary sodium nitrite (N = 40) or placebo (N = 40) during primary PCI for AMI. Ventricular rhythm disturbance was experienced by 100% patients; however, there was no difference in the number between the groups, p = .2196. Non-sustained ventricular tachycardia (NSVT) occurred in 67.5% (27/40) of nitrite-treated patients compared to 89% (35/39) of those treated with placebo (p = .027). There was a significant reduction in both the number of runs (63%, p ≤.0001) and ...

Coronary artery disease, Jan 5, 2018

Chronic total occlusions (CTO) are commonly encountered in patients undergoing coronary angiograp... more Chronic total occlusions (CTO) are commonly encountered in patients undergoing coronary angiography; however, percutaneous coronary intervention (PCI) is infrequently performed owing to technical difficulty, the perceived risk of complications and a lack of randomized data. The aim of this study was to analyse the frequency and outcomes of CTO-PCI procedures in a large contemporary cohort of successive patients. We undertook an observational cohort study of 48 234 patients with stable angina of which 5496 (11.4%) procedures were performed for CTOs between 2005 and 2015 at nine tertiary cardiac centres across London, UK. Outcome was assessed by in-hospital major adverse cardiac events and all-cause mortality at a median follow-up of 4.8 years (interquartile range: 2.2-6.4 years). Over time, there was an increase in the proportion of elective PCI procedures performed for CTOs, but no increase in the absolute number. Overall success rates increased over time (74.3% in 2005 to 81.5% in ...

Open heart, 2018

To date, there have been limited comparisons performed between everolimus-eluting stents (EES) an... more To date, there have been limited comparisons performed between everolimus-eluting stents (EES) and zotarolimus-eluting stents (ZES) in patients with diabetes mellitus (DM). The objectives of this study was to assess the use of second-generation drug-eluting stents in patients with DM, using optical coherence tomography (OCT) to compare the level of stent coverage of Boston Scientific Promus Element EES compared with Medtronic Resolute Integrity ZES.(Clinicaltrials.gov number NCT02060357). This is a single-centre randomised blinded trials assessing two commercially available stents in 60 patients with diabetes (ZES: n=30, EES: n=30). Patients underwent intracoronary assessment at 6 months with OCT assessing stent coverage, malapposition, neointimal thickness and percentage of in-stent restenosis (ISR). Of the 60 patients randomised, 46 patients underwent OCT analysis. There was no difference in baseline characteristics between the two groups. Both Promus Element and Resolute Integrit...

European heart journal. Acute cardiovascular care, 2017

Cardiogenic shock remains a major cause of morbidity and mortality in patients with ST-segment el... more Cardiogenic shock remains a major cause of morbidity and mortality in patients with ST-segment elevation myocardial infarction. We aimed to assess the current trends in cardiogenic shock management, looking specifically at the incidence, use of intra-aortic balloon pump therapy and outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. We undertook an observational cohort study of 21,210 ST-segment elevation myocardial infarction patients treated between 2005-2015 at the eight Heart Attack Centres in London, UK. Patients' details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society percutaneous coronary intervention dataset. There were 1890 patients who presented with cardiogenic shock. The primary outcome was all-cause mortality at a median follow-up of 4.1 years (interquartile range: 2.2-5.8 years). Increasing rates of cardiogenic shock were seen ove...

JRSM Cardiovascular Disease

Proceedings of the National Academy of Sciences of the United States of America, Jan 5, 2017

Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment ref... more Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO3(-)) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitrate-fed mice there is reduced systemic leukocyte rolling and adherence, circulatin...

Journal of the American College of Cardiology, 2016

BMJ open, Dec 20, 2016

The mainstay treatment for reducing the symptoms of angina and long-term risk of heart attacks in... more The mainstay treatment for reducing the symptoms of angina and long-term risk of heart attacks in patients with heart disease is stent implantation in the diseased coronary artery. While this procedure has revolutionised treatment, the incidence of secondary events remains a concern. These repeat events are thought to be due, in part, to continued enhanced platelet reactivity, endothelial dysfunction and ultimately restenosis of the stented artery. In this study, we will investigate whether a once a day inorganic nitrate administration might favourably modulate platelet reactivity and endothelial function leading to a decrease in restenosis. NITRATE-OCT is a double-blind, randomised, single-centre, placebo-controlled phase II trial that will enrol 246 patients with stable angina due to have elective percutaneous coronary intervention procedure with stent implantation. Patients will be randomised to receive 6 months of a once a day dose of either nitrate-rich beetroot juice or nitrat...

Journal of the American College of Cardiology, 2016

Heart (British Cardiac Society), Apr 28, 2016

Recent work suggests that intracoronary nitrite reduces myocardial infarct size following primary... more Recent work suggests that intracoronary nitrite reduces myocardial infarct size following primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI), although the exact mechanisms are unclear. We explored the effects of nitrite on reperfusion-induced inflammation, by assessing the levels of specific pro-inflammatory mediators, chemokines and adhesion molecules in plasma and circulating cell subtypes as exploratory end points in the NITRITE-AMI cohort. Peripheral blood leucocyte subsets, cell adhesion molecules, high-sensitivity C reactive protein (hs-CRP), the monocyte and neutrophil chemoattractants CCL2 and CXCL1, CXCL5, respectively were measured in the blood of patients who received either intracoronary sodium nitrite (N=40) or placebo (N=40) during PPCI for AMI. Major adverse cardiac events were recorded at 3 years post-PPCI. In the placebo-treated patients, total circulating neutrophil numbers and levels of hs-CRP were raised postreperfusion and th...

Journal of the American Heart Association, Jun 27, 2016

ST-segment elevation myocardial infarction is increasingly common in octogenarians, and optimal m... more ST-segment elevation myocardial infarction is increasingly common in octogenarians, and optimal management in this cohort is uncertain. This study aimed to describe the outcomes of octogenarians with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention. We analyzed 10 249 consecutive patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention between 2005 and 2011 at 8 tertiary cardiac centers across London, United Kingdom. The primary end point was all-cause mortality at a median follow-up of 3 years. In total, 1051 patients (10.3%) were octogenarians, with an average age of 84.2 years, and the proportion increased over the study period (P=0.04). In-hospital mortality (7.7% vs 2.4%, P<0.0001) and long-term mortality (51.6% vs 12.8%, P<0.0001) were increased in octogenarians compared with patients aged <80 years, and age was an independent predictor of mortality in a fully adjus...

The American journal of clinical nutrition, Jan 25, 2015

The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic ni... more The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: -0.4, -0.3 m/s) was evident i...

Molecular Nutrition & Food Research, 2015

Ingestion of fruit and vegetables rich in inorganic nitrate (NO3 (-) ) has emerged as an effectiv... more Ingestion of fruit and vegetables rich in inorganic nitrate (NO3 (-) ) has emerged as an effective method for acutely elevating vascular nitric oxide (NO) levels through formation of an NO2 (-) intermediate. As such a number of beneficial effects of NO3 (-) and NO2 (-) ingestion have been demonstrated including reductions in blood pressure, measures of arterial stiffness and platelet activity. The pathway for NO generation from such dietary interventions involves the activity of facultative oral microflora that facilitate the reduction of inorganic NO3 (-) , ingested in the diet, to inorganic NO2 (-) . This NO2 (-) then eventually enters the circulation where, through the activity of one or more of a range of distinct NO2 (-) reductases, it is chemically reduced to NO. This pathway provides an alternative route for in vivo NO generation that could be utilized for therapeutic benefit in those cardiovascular disease states where reduced bioavailable NO is thought to contribute to pathogenesis. Indeed, the cardiovascular benefits of NO2 (-) and NO3 (-) are now starting to be translated in patients in several clinical trials. In this review, we discuss recent evidence supporting the potential utility of delivery of NO3 (-) or NO2 (-) for the treatment of cardiovascular diseases.

Journal of the American College of Cardiology, Jan 23, 2018

A large proportion of patients presenting with non-ST-segment elevation myocardial infarction (NS... more A large proportion of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) present with multivessel disease (MVD). There is uncertainty in the role of complete coronary revascularization in this group of patients. The aim of this study was to investigate the outcomes of complete revascularization compared with culprit vessel-only intervention in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI) for NSTEMI. The authors undertook an observational cohort study of 37,491 NSTEMI patients treated between 2005 and 2015 at the 8 heart attack centers in London. Clinical details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society (BCIS) PCI dataset. A total of 21,857 patients (58.3%) presented with NSTEMI and MVD. Primary outcome was all-cause mortality at a median follow-up of 4.1 years (interquartile range: 2.2 to 5.8 years). A total of 11,737 (53.7%) patients und...

Journal of the American College of Cardiology

Journal of the American College of Cardiology

Journal of cardiovascular pharmacology and therapeutics, Jan 6, 2018

In the follow-up of patients in a trial of intracoronary sodium nitrite given during primary perc... more In the follow-up of patients in a trial of intracoronary sodium nitrite given during primary percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI), we found a reduction in the incidence of major adverse cardiac events (MACEs). Specifically, MACE rates were 5.2% versus 25.0% with placebo at 3 years ( P = .013). Such MACE reductions should also be associated with economic benefit. Thus, we assessed the cost utility of sodium nitrite therapy versus standard primary PCI only. We developed a model to simulate costs and quality-adjusted life years (QALYs) over the first 36 months after ST-Segment Elevation Myocardial Infarction (STEMI). Decision tree analysis was used to assess different potential cardiovascular outcomes after STEMI for patients in both treatment groups. Model inputs were derived from the NITRITE-AMI study. Cost of comparative treatments and follow-up in relation to cardiovascular events was calculated from the United Kingdom National Health Ser...

Heart and vessels, Jan 27, 2018

Transradial access is increasingly used for coronary angiography and percutaneous coronary interv... more Transradial access is increasingly used for coronary angiography and percutaneous coronary intervention, however, femoral access remains necessary for numerous procedures, including complex high-risk interventions, structural procedures, and procedures involving mechanical circulatory support. Optimising the safety of this approach is crucial to minimize costly and potentially life-threatening complications. We initiated a quality improvement project recommending routine fluoroscopic guidance (femoral head), and upfront femoral angiography should be performed to assess for location and immediate complications. We assessed the effect of these measures on the rate of vascular complications. Data were collected prospectively on 4534 consecutive patients undergoing femoral coronary angiographic procedures from 2015 to 2017. The primary end-point was any access complication. Outcomes were compared pre and post introduction including the use of an Interrupted Time-Series (ITS) analysis. 1...

Free radical biology & medicine, Jan 20, 2018

Oral reduction of nitrate to nitrite is dependent on the oral microbiome and is the first step of... more Oral reduction of nitrate to nitrite is dependent on the oral microbiome and is the first step of an alternative mammalian pathway to produce nitric oxide in humans. Preliminary evidence suggests important sex differences in this pathway. We prospectively investigated sex-differences following inorganic nitrate supplementation on nitrate/nitrite levels and vascular function, and separately examined sex differences in oral nitrate reduction, and oral microbiota by 16S rRNA profiling. At baseline, females exhibit higher nitrite levels in all biological matrices despite similar nitrate levels to males. Following inorganic nitrate supplementation, plasma nitrite was increased to a significantly greater extent in females than in males and pulse wave velocity was only reduced in females. Females exhibited higher oral bacterial nitrate-reducing activity at baseline and after nitrate supplementation. Despite these differences, there were no differences in the composition of either the total...

International journal of cardiology, Sep 1, 2018

Pre-clinical evidence suggests delivery of nitric oxide (NO) through administration of inorganic ... more Pre-clinical evidence suggests delivery of nitric oxide (NO) through administration of inorganic nitrite suppresses arrhythmias resulting from acute ischaemia and reperfusion (I/R). To date no assessment of whether inorganic nitrite might limit reperfusion arrhythmia has occurred in man, therefore we explored the effects on I/R-induced ventricular arrhythmias in the NITRITE-AMI cohort. In the NITRITE-AMI cohort, Holter analysis was performed prior to and for 24 h after primary PCI in 80 patients who received either intra-coronary sodium nitrite (N = 40) or placebo (N = 40) during primary PCI for AMI. Ventricular rhythm disturbance was experienced by 100% patients; however, there was no difference in the number between the groups, p = .2196. Non-sustained ventricular tachycardia (NSVT) occurred in 67.5% (27/40) of nitrite-treated patients compared to 89% (35/39) of those treated with placebo (p = .027). There was a significant reduction in both the number of runs (63%, p ≤.0001) and ...

Coronary artery disease, Jan 5, 2018

Chronic total occlusions (CTO) are commonly encountered in patients undergoing coronary angiograp... more Chronic total occlusions (CTO) are commonly encountered in patients undergoing coronary angiography; however, percutaneous coronary intervention (PCI) is infrequently performed owing to technical difficulty, the perceived risk of complications and a lack of randomized data. The aim of this study was to analyse the frequency and outcomes of CTO-PCI procedures in a large contemporary cohort of successive patients. We undertook an observational cohort study of 48 234 patients with stable angina of which 5496 (11.4%) procedures were performed for CTOs between 2005 and 2015 at nine tertiary cardiac centres across London, UK. Outcome was assessed by in-hospital major adverse cardiac events and all-cause mortality at a median follow-up of 4.8 years (interquartile range: 2.2-6.4 years). Over time, there was an increase in the proportion of elective PCI procedures performed for CTOs, but no increase in the absolute number. Overall success rates increased over time (74.3% in 2005 to 81.5% in ...

Open heart, 2018

To date, there have been limited comparisons performed between everolimus-eluting stents (EES) an... more To date, there have been limited comparisons performed between everolimus-eluting stents (EES) and zotarolimus-eluting stents (ZES) in patients with diabetes mellitus (DM). The objectives of this study was to assess the use of second-generation drug-eluting stents in patients with DM, using optical coherence tomography (OCT) to compare the level of stent coverage of Boston Scientific Promus Element EES compared with Medtronic Resolute Integrity ZES.(Clinicaltrials.gov number NCT02060357). This is a single-centre randomised blinded trials assessing two commercially available stents in 60 patients with diabetes (ZES: n=30, EES: n=30). Patients underwent intracoronary assessment at 6 months with OCT assessing stent coverage, malapposition, neointimal thickness and percentage of in-stent restenosis (ISR). Of the 60 patients randomised, 46 patients underwent OCT analysis. There was no difference in baseline characteristics between the two groups. Both Promus Element and Resolute Integrit...

European heart journal. Acute cardiovascular care, 2017

Cardiogenic shock remains a major cause of morbidity and mortality in patients with ST-segment el... more Cardiogenic shock remains a major cause of morbidity and mortality in patients with ST-segment elevation myocardial infarction. We aimed to assess the current trends in cardiogenic shock management, looking specifically at the incidence, use of intra-aortic balloon pump therapy and outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. We undertook an observational cohort study of 21,210 ST-segment elevation myocardial infarction patients treated between 2005-2015 at the eight Heart Attack Centres in London, UK. Patients' details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society percutaneous coronary intervention dataset. There were 1890 patients who presented with cardiogenic shock. The primary outcome was all-cause mortality at a median follow-up of 4.1 years (interquartile range: 2.2-5.8 years). Increasing rates of cardiogenic shock were seen ove...

JRSM Cardiovascular Disease

Proceedings of the National Academy of Sciences of the United States of America, Jan 5, 2017

Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment ref... more Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO3(-)) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitrate-fed mice there is reduced systemic leukocyte rolling and adherence, circulatin...

Journal of the American College of Cardiology, 2016

BMJ open, Dec 20, 2016

The mainstay treatment for reducing the symptoms of angina and long-term risk of heart attacks in... more The mainstay treatment for reducing the symptoms of angina and long-term risk of heart attacks in patients with heart disease is stent implantation in the diseased coronary artery. While this procedure has revolutionised treatment, the incidence of secondary events remains a concern. These repeat events are thought to be due, in part, to continued enhanced platelet reactivity, endothelial dysfunction and ultimately restenosis of the stented artery. In this study, we will investigate whether a once a day inorganic nitrate administration might favourably modulate platelet reactivity and endothelial function leading to a decrease in restenosis. NITRATE-OCT is a double-blind, randomised, single-centre, placebo-controlled phase II trial that will enrol 246 patients with stable angina due to have elective percutaneous coronary intervention procedure with stent implantation. Patients will be randomised to receive 6 months of a once a day dose of either nitrate-rich beetroot juice or nitrat...

Journal of the American College of Cardiology, 2016

Heart (British Cardiac Society), Apr 28, 2016

Recent work suggests that intracoronary nitrite reduces myocardial infarct size following primary... more Recent work suggests that intracoronary nitrite reduces myocardial infarct size following primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI), although the exact mechanisms are unclear. We explored the effects of nitrite on reperfusion-induced inflammation, by assessing the levels of specific pro-inflammatory mediators, chemokines and adhesion molecules in plasma and circulating cell subtypes as exploratory end points in the NITRITE-AMI cohort. Peripheral blood leucocyte subsets, cell adhesion molecules, high-sensitivity C reactive protein (hs-CRP), the monocyte and neutrophil chemoattractants CCL2 and CXCL1, CXCL5, respectively were measured in the blood of patients who received either intracoronary sodium nitrite (N=40) or placebo (N=40) during PPCI for AMI. Major adverse cardiac events were recorded at 3 years post-PPCI. In the placebo-treated patients, total circulating neutrophil numbers and levels of hs-CRP were raised postreperfusion and th...

Journal of the American Heart Association, Jun 27, 2016

ST-segment elevation myocardial infarction is increasingly common in octogenarians, and optimal m... more ST-segment elevation myocardial infarction is increasingly common in octogenarians, and optimal management in this cohort is uncertain. This study aimed to describe the outcomes of octogenarians with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention. We analyzed 10 249 consecutive patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention between 2005 and 2011 at 8 tertiary cardiac centers across London, United Kingdom. The primary end point was all-cause mortality at a median follow-up of 3 years. In total, 1051 patients (10.3%) were octogenarians, with an average age of 84.2 years, and the proportion increased over the study period (P=0.04). In-hospital mortality (7.7% vs 2.4%, P<0.0001) and long-term mortality (51.6% vs 12.8%, P<0.0001) were increased in octogenarians compared with patients aged <80 years, and age was an independent predictor of mortality in a fully adjus...

The American journal of clinical nutrition, Jan 25, 2015

The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic ni... more The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: -0.4, -0.3 m/s) was evident i...

Molecular Nutrition & Food Research, 2015

Ingestion of fruit and vegetables rich in inorganic nitrate (NO3 (-) ) has emerged as an effectiv... more Ingestion of fruit and vegetables rich in inorganic nitrate (NO3 (-) ) has emerged as an effective method for acutely elevating vascular nitric oxide (NO) levels through formation of an NO2 (-) intermediate. As such a number of beneficial effects of NO3 (-) and NO2 (-) ingestion have been demonstrated including reductions in blood pressure, measures of arterial stiffness and platelet activity. The pathway for NO generation from such dietary interventions involves the activity of facultative oral microflora that facilitate the reduction of inorganic NO3 (-) , ingested in the diet, to inorganic NO2 (-) . This NO2 (-) then eventually enters the circulation where, through the activity of one or more of a range of distinct NO2 (-) reductases, it is chemically reduced to NO. This pathway provides an alternative route for in vivo NO generation that could be utilized for therapeutic benefit in those cardiovascular disease states where reduced bioavailable NO is thought to contribute to pathogenesis. Indeed, the cardiovascular benefits of NO2 (-) and NO3 (-) are now starting to be translated in patients in several clinical trials. In this review, we discuss recent evidence supporting the potential utility of delivery of NO3 (-) or NO2 (-) for the treatment of cardiovascular diseases.