Hyperlipidemias: Jardine AG

Holdaas H, Fellström B, Jardine AG, Anonymous00166. · No affiliation provided · Am J Transplant. · Pubmed #15888072 No free full text.

This publication has no abstract.

Wan RK, Mark PB, Jardine AG. · BHF Cardiovascular Research Centre, University of Glasgow, and Renal Transplant Unit, Western Infirmary, Glasgow, United Kingdom. · Semin Dial. · Pubmed #17991195 No free full text.

Abstract: In the general population, elevated cholesterol is associated with cardiovascular disease and mortality and lowering cholesterol is associated with improved outcomes. This reflects the predominance of isolated atherosclerotic coronary disease in the general population. In patients with renal disease, however, the relationship between serum lipids and cardiovascular outcomes is much less clear and even reversed. In our opinion, the relationship between cholesterol and coronary disease is obscured by high levels of co-morbid disease, malnutrition, inflammation, atypical dyslipidemia and the fact that myocardial infarction is not the typical presentation of cardiovascular disease in patients with renal disease. Thus, cholesterol lowering will still be effective in patients with chronic kidney diseases.

Fellström BC, Holdaas H, Jardine AG. · Department of Medicine, Western Infirmary, Glasgow, United Kingdom. · Kidney Int Suppl. · Pubmed #12694345 No free full text.

Abstract: BACKGROUND: The risk of cardiovascular complications is markedly increased in patients on dialysis treatment. This includes cardiac disease, stroke, and peripheral vascular disease. The mortality in dialysis patients is markedly higher compared to a nonuremic population. There are several cardiovascular (CV) risk factors that are unique to this population, one of which is dyslipidemia. Uremic patients do not usually develop hypercholesterolemia, but rather are characterized by high levels of very low density lipoprotein (VLDL) triglycerides, low high density lipoprotein (HDL) cholesterol, and elevated levels of modified low density lipoprotein (LDL) particles, which are particularly harmful to the vascular wall. HMG-CoA reductase inhibitors (statins) have been proven to be very efficient in reducing CV events in a nonrenal population. There are several landmark trials that have demonstrated that statins reduce the mortality in cardiovascular disease (CVD) in populations with normal, or close to normal, renal function. There are some observational registry data indicating that this may also be true in hemodialysis (HD) patients, but no prospective controlled trial has been performed to date. METHODS: We present the rationale for, and a brief outline of, a randomized placebo-controlled trial using a novel drug, rosuvastatin, in HD patients, to target cardiovascular events (the AURORA study). This study will include close to 3000 male and female HD patients, aged 50-80 years. The study is event driven and it has been estimated that it will run for a follow-up time close to four years. CONCLUSION: There is a sound rationale for making a randomized placebo-controlled statin trial in HD patients, with the objective to demonstrate an effect on CV mortality and morbidity.

Jardine AG, McLaughlin K. · University Department of Medicine & Therapeutics, Western Infirmary, Glasgow, UK. · Heart. · Pubmed #11559693 links to  free full text

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Morris ST, Jardine AG. · Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK. · J Nephrol. · Pubmed #10858970 No free full text.

Abstract: Chronic renal failure (CRF) is associated with a 20-fold increased risk of cardiovascular death, two principal mechanisms being: sudden, arrhythmic death associated with left ventricular hypertrophy, and ischaemic heart disease, associated with accelerated atherosclerosis. In recent years, the vascular endothelium has been recognised as a large and complex endocrine organ, with many important physiological functions including the control of vascular tone. Endothelial dysfunction, commonly characterised by reduced production of the vasodilator nitric oxide (NO), is thought to be a key initial event in the development of atherosclerosis and is present in patients with hypertension and hyperlipidaemia. While these cardiovascular risk factors are also prevalent in CRF, other factors more specific to uraemia such as accumulation of homocysteine and asymmetric dimethylarginine (endogenous inhibitor of NO synthase) may impair endothelial function. Modulation of endothelial function in CRF may offer a novel strategy to reduce cardiovascular disease.

Mark PB, Johnston N, Groenning BA, Foster JE, Blyth KG, Martin TN, Steedman T, Dargie HJ, Jardine AG. · Division of Cardiovascular and Medical Sciences, Gardiner Institute, University of Glasgow, UK. · Kidney Int. · Pubmed #16508657 No free full text.

Abstract: Patients with end stage renal failure (ESRF) have an increased risk of premature cardiovascular disease. Left ventricular (LV) abnormalities, so called 'uremic cardiomyopathy', are associated with poorer outcome. Cardiac magnetic resonance imaging (CMR) accurately defines LV dimensions and identifies underlying myocardial pathology. We studied the relationship between LV function and myocardial pathology in ESRF patients with CMR. A total of 134 patients with ESRF underwent CMR. LV function was assessed with further images acquired after gadolinium-diethylentriaminepentaacetic acid (DTPA). The presence of myocardial fibrosis was indicated by late gadolinium enhancement (LGE). Two main myocardial pathologies were identified. A total of 19 patients (14.2%) displayed 'subendocardial LGE' representing myocardial infarction, which was associated with conventional cardiovascular risk factors including a history of ischemic heart disease (IHD) (P < 0.001), hypercholesterolemia (P < 0.05), and diabetes (P < 0.01). Patients with subendocardial LGE had greater LV mass (P < 0.05), LV dilation (P < 0.01), and LV systolic dysfunction (P < 0.001) compared to patients with no evidence of LGE. The second pattern, 'diffuse LGE', seen in 19 patients (14.2%) appeared to represent regional areas of diffuse myocardial fibrosis. Diffuse LGE was associated with greater LV mass compared to patients without LGE (P < 0.01) but not systolic dysfunction. In total, 28.4% of all patients exhibited evidence of myocardial fibrosis demonstrated by LGE. In contrast to published literature describing three forms of uremic cardiomyopathy - left ventricular hypertrophy (LVH), dilation, and systolic dysfunction, we have shown that LVH is the predominant cardiomyopathy specific to uremia, while LV dilation and systolic dysfunction are due to underlying (possibly silent) ischemic heart disease.

Jardine AG, Fellström B, Logan JO, Cole E, Nyberg G, Grönhagen-Riska C, Madsen S, Neumayer HH, Maes B, Ambühl P, Olsson AG, Pedersen T, Holdaas H. · University of Glasgow, UK. · Am J Kidney Dis. · Pubmed #16129216 No free full text.

Abstract: BACKGROUND: Renal transplantation is associated with an increased risk for premature cardiovascular disease. We analyzed the data in the placebo arm of Assessment of Lescol in Renal Transplantation (ALERT) to improve our understanding of the relationship between cardiovascular risk factors and outcomes in this unique population. METHODS: We performed Cox survival analysis for myocardial infarction, cardiac death, and noncardiac death in 1,052 patients recruited to the placebo arm of ALERT. These subjects were aged 30 to 75 years, had stable graft function at least 6 months after transplantation, had a serum total cholesterol level between 155 and 348 mg/dL (4 and 9 mmol/L), and were receiving cyclosporine-based immunosuppression. RESULTS: The results confirm previous studies. In multivariate analysis, preexisting coronary heart disease (hazard ratio [HR], 3.69; P < 0.001), total cholesterol level (HR, 1.55 per 50 mg/dL; P = 0.0045), and prior acute rejection (HR, 2.36; P = 0.0023) were independent risk factors. Conversely, independent risk factors for cardiac death were age (HR, 1.58 per decade; P = 0.0033), diabetes (HR, 3.35; P = 0.0002), ST-T changes on the ECG (HR, 3.17; P = 0.0004), and serum creatinine level (HR, 2.65 per milligram per deciliter; P < 0.0001). CONCLUSION: This analysis confirms that renal transplant recipients share risk factors for myocardial infarction and cardiac death with the general population. However, the pattern of risk factors and their relationship with outcomes is atypical, highlighting the unique nature of cardiovascular risk in transplant recipients.