Reciprocal relations between cardiovascular disease, employment, financial insecurity, and post cardiac event recovery among Maori men: a case series.

BACKGROUND: Disparities in cardiovascular outcomes between Maori and non-Maori persist despite technological advances in the treatment of cardiovascular disease and improved service provision. Little is known about how social determinants of health, such as income [in]security affect Maori men's access, treatment, and recovery from cardiovascular disease. This paper explores the contexts within which cardiovascular disease is experienced and healthcare becomes embedded. METHODS: This study utilized a case-comparative narrative approach to document and make sense of the patient experiences of four male Maori patients who, in the previous 6 months, had come through cardiac investigation and treatment at Waikato Hospital, a large tertiary cardiac center in New Zealand. Participant accounts were elicited using a culturally patterned narrative approach to case development, informed by Kaupapa Maori Research practices. It involved three repeat 1-3-hour interviews recorded with participants (12 interviews); the first interviews took place 5-16 weeks after surgery/discharge. RESULTS: Each of the four case studies firstly details a serious cardiac event(s) before describing the varying levels of financial worry they experienced. Major financial disruptions to their lives were at the forefront of the concerns of those facing financial insecurity-as opposed to their medical problems. Financial hardship within the context of an unresponsive welfare system impacted the access to care and access to funding contributed to psychological distress for several participants. Economic security and reciprocal relationships between employers and employees facilitated positive treatment experiences and recovery. CONCLUSION: Findings suggest that although multiple factors influence participant experiences and treatment outcomes, financial [in]security, and personal income is a key determinant. The heterogeneity in participant narratives suggests that although general inequities in health may exist for Maori as a population group, these inequities do not appear to be uniform. We postulate diverse mechanisms, by which financial insecurity may adversely affect outcomes from treatment and demonstrate financial security as a significant determinant in allowing patients to respond to and recover from cardiovascular disease more effectively.

Characteristics, trends and outcomes in acute coronary syndromes in the renal replacement therapy population: a 10-year retrospective analysis of the Midlands Region, New Zealand.

Acute coronary syndrome (ACS) is one of the leading causes of mortality in the renal replacement therapy (RRT) population. We aimed to understand the characteristics, trends and outcomes of ACS in our local RRT population as a means to improve care and outcomes for this high-risk population. Using the ANZACS-QI database, we conducted a retrospective analysis of all ACS occurring in RRT patients between 1 January 2010-31 December 2019 managed at Waikato Hospital (n=135 at index ACS). In our cohort made up predominantly of Maori (55%) and European (34%) patients, 58% had diabetic nephropathy as their primary disease. Twenty-seven percent presented atypically and 65% had a delay of >72 hours from diagnosis to angiogram. There was a 49% mortality rate at one year post-index ACS. Factors associated with mortality at one year included: atypical presentation (chi-square statistic (X2) 7.250; p=0.0071), troponin delta >20% (X2 5.682; p=0.0171), peak troponin (point biserial correlation; r=0.2086; p=0.0473) and no revascularisation (X2 5.2419; p=0.0221). The findings in our cohort reiterate that patients on RRT are a vulnerable population who have poor outcomes associated with ACS, driven by multifactorial delays in diagnosis and treatment.

Leukocyte telomere length is associated with high-risk plaques on virtual histology intravascular ultrasound and increased proinflammatory activity.

OBJECTIVE: Leukocyte telomere length (LTL), a marker of cellular senescence, is inversely associated with cardiovascular events. However, whether LTL reflects plaque extent or unstable plaques, and the mechanisms underlying any association are unknown. METHODS AND RESULTS: One hundred seventy patients with stable angina or acute coronary syndrome referred for percutaneous coronary intervention underwent 3-vessel virtual histology intravascular ultrasound; 30 372 mm of intravascular ultrasound pullback and 1096 plaques were analyzed. LTL was not associated with plaque volume but was associated with calcified thin-capped fibroatheroma (OR, 1.24; CI, 1.01-1.53; P=0.039) and total fibroatheroma numbers (OR, 1.19; CI, 1.02-1.39; P=0.027). Monocytes from coronary artery disease patients showed increased secretion of proinflammatory cytokines. To mimic leukocyte senescence, we disrupted telomeres and binding and expression of the telomeric protein protection of telomeres protein-1, inducing DNA damage. Telomere disruption increased monocyte secretion of monocyte chemoattractant protein-1, IL-6, and IL-1ß and oxidative burst, similar to that seen in coronary artery disease patients, and lymphocyte secretion of IL-2 and reduced lymphocyte IL-10. CONCLUSIONS: Shorter LTL is associated with high-risk plaque morphology on virtual histology intravascular ultrasound but not total 3-vessel plaque burden. Monocytes with disrupted telomeres show increased proinflammatory activity, which is also seen in coronary artery disease patients, suggesting that telomere shortening promotes high-risk plaque subtypes by increasing proinflammatory activity.

Intensive statin therapy in acute coronary syndromes.

Acute coronary syndromes (ACS) represent an enormous disease burden, especially in the Western world, where they are one of the largest causes of mortality and morbidity. Patients suffering an acute coronary event are at very high risk of further coronary events, and although improvements in medical therapy over the past two decades have significantly reduced the risk, it remains high. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are now fully established in the primary and secondary prevention of stable coronary heart disease, and recently a substantial body of evidence has proven their efficacy in ACS. This paper examines the evidence for statin use in ACS.

Ageing and atherosclerosis: Mechanisms and therapeutic options.

Atherosclerosis is the cause of most heart attacks and strokes, and is par excellence, a disease of ageing. Whilst disease prevalence and incidence increases with increasing decade of life, there is also evidence of accelerated cellular ageing in atherosclerosis. Such evidence includes impaired cell proliferation, early culture senescence and cell cycle markers of senescence in vitro and in vivo. Cell senescence is also characterised by loss of telomeres from the ends of chromosomes. Cellular ageing increases with disease severity, acting as a marker for disease, but also directly promotes atherosclerosis. Cellular ageing appears to be due to both abnormal proliferation of cells in an attempt to repair vessel damage, and a response to the damage itself. This review summarises the evidence of vascular cell senescence in atherosclerosis, the causes and consequences of accelerated cellular ageing in atherosclerosis, and identifies potential therapeutic options for both prevention and treatment.

Predominance of Th2 response in human abdominal aortic aneurysm: mistaken identity for IL-4-producing NK and NKT cells?

Abdominal aortic aneurysm (AAA) is a complex remodeling process that involves both synthesis and degradation of extracellular matrix proteins in the aortic wall, leading to decreased tensile strength, progressive dilation and eventual rupture. Chronic inflammation, increased local production of elastin-degrading proteases by inflammatory cells and destruction of medial elastic lamellae play important roles in aneurysm progression. Neovascularization in all layers of the arterial wall is prominent and angiogenesis can facilitate chronic inflammation. It is still unclear what initiates aneurysmal dilation and what determines its progression. The complex nature of the process has defied elucidation. Apart from macrophages, the predominant immune cell infiltrates reported so far are CD3(+)T cells that express CD4 and CD8. Infiltrates of type 2 Th cells and their production of IL-4 and IL-5 have been implicated in AAA development. However, NKT and NK cells have a Th0 cytokine profile and can also produce type 2 as well as type 1 (IL-2 and IFNgamma) cytokines. We have demonstrated the presence of NK and NKT cells in AAA tissue. With their growing importance in autoimmunity and transplantation, they may play a role in AAA development. Therefore, there is a need to use a combination of T and NK markers to fully characterize both innate and adaptive lymphoid cell subsets in local inflammatory infiltrates in order to elucidate their roles in AAA progression.

Atherosclerotic abdominal aortic aneurysm and the interaction between autologous human plaque-derived vascular smooth muscle cells, type 1 NKT, and helper T cells.

Immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation, and apoptosis are pathological hallmarks of atherosclerosis. The multifocal, chronic, and inflammatory nature of this disease of the cardiovascular system complicates targeted cellular therapy and emphasizes the need to understand the role and interaction of immune cells with VSMCs. We characterized the immune cell subsets present in human atherosclerotic tissue derived from atherosclerotic abdominal aortic aneurysm (AAA) and expanded them to study their interaction with autologous plaque-derived VSMCs in vitro. We show here that apart from T lymphocytes, plaque infiltrates consist of lots of NK cells and significant proportions of NKT cells that express T cell receptor (TCR) alphabeta, CD4, and the NK markers CD56 and CD161. The infiltrates are predominantly IFN-gamma-producing Type 1 lymphoid cells. When cocultured, the T and NKT cells adhere to VSMCs. CD4+ T cells enhance VSMC proliferation. VSMCs in turn enhance CD4+CD161+ NKT but not CD4+ or CD8+ T cell proliferation. CD4+CD161+ NKT cells inhibit VSMC proliferation by inducing apoptosis. Our results suggest that the interactions of Type 1 CD4+ T and CD4+CD161+ NKT cells with VSMCs may regulate VSMC proliferation and death respectively in atherosclerosis and the balance of these interactions could determine plaque stability.

NKT cell subsets in infection and inflammation.

We recently identified two stably expressed cell surface markers, IL-18R and ST2L, which are selectively expressed on T1/NK1 and T2/NK2 cells, respectively. Here we use these molecules in direct ex vivo analysis of PBMCs from patients with AIDS, psoriasis (PS) atherosclerosis and to show the importance of these markers as determinants of the functional dichotomy of lymphocyte subsets, in particular NKT. In a cohort of 22 HIV patients made up of a mixture of long term non-progressors, seroconvertors, progressors and asymptomatics, we found a clear NKT1 to NKT2 shift (P=0.001) in the HIV-infected individuals. We also show a predominance of NKT2 cells over NKT1 cells in the PBMCs of patients with mild to moderate PS (N=13, P=0.005) but not in atopic dermatitis or healthy controls. However, in patients (N=6) requiring surgery for aneurysm, a predominance of Type 1 (IL-18R(+)) NKT lymphocytes over NKT2 was detected among infiltrating lymphocytes isolated from atherosclerotic plaques. Our data therefore demonstrate that ST2L and IL-18R could serve as important determinants of the immune status of human diseases.