M. Barbir

High prevalence of hypertriglyceridaemia and apolipoprotein abnormalities in coronary artery disease.

Serum lipids and apolipoproteins A-I and B were measured in 174 men aged less than 60 with angiographically confirmed coronary artery disease and in 572 healthy control men. Two thirds of the patients had raised age-corrected values of fasting serum cholesterol and/or triglyceride and/or a low high density lipoprotein (HDL) cholesterol compared with the controls. Eighteen (30%) of the 61 normolipidaemic patients had a concentration of serum apolipoprotein A-I below the 5th percentile of 233 controls. In normolipidaemic patients on beta blockers the relative prevalence of serum low density lipoprotein (LDL)-apolipoprotein B values above the 95th percentile of 339 controls was significantly increased. Discriminant function analysis showed that a raised concentration of serum triglyceride was the best discriminant between patients and controls, with raised LDL-apolipoprotein B and reduced apolipoprotein A-I coming second only to triglyceride in analyses where each was separately compared with all the lipid variables. These associations were highly significant and were independent of other influences, including beta blockade. These findings re-emphasise the importance of hypertriglyceridaemia as a risk factor and confirm that apolipoprotein abnormalities occur frequently in coronary disease, even in normolipidaemic patients.

Efficacy criteria and cholesterol targets for LDL apheresis.

Low density lipoprotein (LDL) apheresis is now accepted as the treatment of choice for patients with homozygous familial hypercholesterolaemia and for heterozygotes with cardiovascular disease refractory to lipid-lowering drug therapy. However, a paucity of evidence has meant that detailed guidance on the extent of cholesterol reduction required to prevent the onset or progression of cardiovascular disease in these high risk patients is lacking. This review defines criteria for expressing the efficacy of apheresis, proposes target levels of total and LDL cholesterol for homozygotes and heterozygotes based on recent follow-up studies and suggests a scheme for monitoring cardiovascular disease in these patients. Establishing a uniform approach to data collection would facilitate the setting up of national or multi-national registers and might eventually provide the information needed to formulate evidence-based guidelines for LDL apheresis.

Severe hypercholesterolaemia: Therapeutic goals and eligibility criteria for LDL apheresis in Europe

Purpose of review Despite the use of currently available lipid-lowering therapies, a significant proportion of patients with severe hypercholesterolaemia do not reach treatment goals and consequently remain at increased risk for cardiovascular disease (CVD). On the basis of clinical experience, these patients tend to have the most severe forms of familial hypercholesterolaemia or markedly elevated LDL cholesterol (LDL-C) levels but are unable to tolerate statin therapy. Recent findings LDL apheresis is currently the best treatment option (or treatment rescue) to bring these patients closer to therapeutic LDL objectives, and has been shown to reduce the risk of CVD along with LDL-C levels. However, criteria for LDL apheresis eligibility and the percentage of patients receiving treatment vary widely from country to country across Europe. Despite the proven benefits of LDL apheresis, access to this procedure remains limited because of its high cost and low availability, reflecting inherent limitations of this treatment modality. Summary There is a need to both better define the patient population eligible for LDL apheresis and to create unified European guidelines governing the use of apheresis. In addition to improving access to apheresis where appropriate, new therapies are needed to further decrease LDL-C and reduce the ongoing CVD risk in patients with severe hypercholesterolaemia.

Lipoprotein(a) and accelerated coronary artery disease in cardiac transplant recipients

High concentrations of serum lipoprotein(a) (Lp(a)) are associated with an increased risk of atherosclerotic vascular disease in the nontransplanted population. However, its relation with accelerated coronary artery disease (CAD) in cardiac transplant recipients has not been reported. We measured serum Lp(a) in 130 cardiac transplant recipients undergoing routine follow-up, which included annual coronary angiography. The median Lp(a) concentration in 33 patients with CAD was 71 mg/dl, which was significantly higher than the corresponding value of 22 mg/dL in the 97 patients without CAD (p = 0.0006). Multivariant analysis showed the serum Lp(a) value to be a higher significant risk factor for CAD irrespective of the other factors included in the regression analysis. Thus a high concentration of serum Lp(a) is an important, independent risk factor for the development of accelerated CAD in transplant recipients.

Low-dose simvastatin for the treatment of hypercholesterolaemia in recipients of cardiac transplantation

There is increasing evidence that hypercholesterolaemia is an important contributor to the development of accelerated coronary arterial disease in the cardiac allograft. The optimal drug therapy of hypercholesterolaemia in recipients after cardiac transplantation, however, has not been defined. Simvastatin (an inhibitor of hydroxy-methyl glutaryl-coenzyme A reductase), at a dose of 10 mg/day, was administered to 12 recipients with serum total cholesterol greater than or equal to 7.8 mmol/l and serum triglyceride less than or equal to 4.5 mmol/l refractory to dietary measures during a follow-up period of 1-5 years after cardiac transplantation. All patients received maintenance doses of cyclosporin A and, in some instances, azathioprine and prednisolone. After 2 months treatment with simvastatin, serum total cholesterol was significantly reduced from 8.8 +/- 0.3 mmol/l (mean +/- SEM) to 5.5 +/- 0.5 mmol/l, P less than 0.001, low density cholesterol from 6.6 +/- 0.4 to 3.8 +/- 0.3 mmol/l, P less than 0.001 and triglycerides from 2.4 +/- 0.2 mmol/l to 1.8 +/- 0.2 mmol/l, P less than 0.005. These changes were maintained after a period of treatment of 8 months. Serum high density cholesterol, hepatic transaminase levels, serum creatinine, creatine kinase and cyclosporin A blood levels were not altered by treatment with simvastatin. It is concluded that, in this study group, low-dose simvastatin appears to be well tolerated and has favourable lipid modifying properties.

Cardiac rehabilitation for the treatment of women with chest pain and normal coronary arteries

Objective: To explore cardiac rehabilitation (CR) as a treatment for psychological and physiological morbidity in women with chest pain and normal coronary arteries (cardiac syndrome X). Design: Sixty-four women aged 57.3 ± 8.6 years (mean ± SD) with cardiac syndrome X were randomly assigned to an 8-week phase III CR exercise program or symptom monitoring control. All women completed the Hospital Anxiety and Depression Scale, Health Anxiety Questionnaire, and Short Form-36 before and after intervention and at the 8-week follow-up. CR patients underwent physical assessment before and after CR. Results: After CR, patients demonstrated improved symptom severity (2.0 ± 0.8 vs 1.26 ± 1.1, P = 0.009), Hospital Anxiety and Depression Scale depression score (8.0 ± 3.4 vs 6.4 ± 3.1, P = 0.04), total Health Anxiety Questionnaire score (12.0 ± 5.5 vs 9.5 ± 6.0, P = 0.008), health worry (4.5 ± 3.1 vs 3.52 ± 2.4, P = 0.025) and interference (2.4 ± 1.8 vs 1.6 ± 1.8, P = 0.004), SF-36 physical functioning (53.1 ± 20.4 vs 62.3 ± 23.9, P = 0.006), energy (36.3 ± 20.7 vs 49.8 ± 19.1, P < 0.001), pain (49.9 ± 20.7 vs 58.1 ± 22.9, P = 0.028), and general health (48.8 ± 17.9 vs 57.6 ± 17.0, P = 0.01) not found among the control women. Improvements were maintained at follow-up. CR patients showed significant improvements in Shuttle Walk Test performance (326.8 ± 111.0 vs 423.6 ± 133.2 m, P < 0.001), diastolic blood pressure (84.7 ± 9.4 vs 79.7 ± 7.3 mm Hg, P = 0.007), and body mass index (29.1 ± 6.0 vs 28.4 ± 6.17 kg/m2, P = 0.003). Conclusions: An 8-week phase III CR program improves exercise tolerance, quality of life, psychological morbidity, symptom severity, and cardiovascular risk factors in women with cardiac syndrome X.

Coronary artery surgery in women compared with men: analysis of coronary risk factors and in-hospital mortality in a single centre.

OBJECTIVE--To determine differences in coronary risk factors between women and men and their relation to in-hospital mortality associated with coronary artery bypass grafting. DESIGN--Prospective observational study. SETTING--A regional cardiothoracic centre. PATIENTS--482 (362 (75%) men and 120 (25%) women) consecutive patients who had primary isolated coronary artery bypass grafting. RESULTS--The women were on average three years older than the men (63 v 60 years, P < 0.001). Women more frequently had hypertension (47% v 33%, P < 0.01), diabetes mellitus (21% v 10%, P < 0.005), hypothyroidism (9% v 2%, P < 0.003), and a family history of premature coronary heart disease (49% v 31%, P < 0.0006). More of the men were cigarette smokers (67% v 45%, P > 0.00001). Many of the women and men had dyslipidaemia. Postmenopausal women had a higher concentration of serum total cholesterol than men of a comparable age, (7.3 mmol/l v 6.5 mmol/l, P = 0.0002). Although arterial grafts were often used in both sexes, they were more often used in men than in women (91% v 78% respectively, P = 0.0003). In-hospital mortality was 2.1% (1.4% in men and 4.2% in women, P = 0.14). The estimated one year probability of survival in men who had survived 30 days was 0.99 with 95% confidence interval 0.98 to approximately 1 while that for women was 0.97 with 95% confidence interval 0.91 to approximately 1. Univariate analysis showed that preoperative history of diabetes mellitus was a predictor of mortality (P = 0.03). CONCLUSION--There were differences in the incidence and type of risk factors in men and women who had coronary artery bypass grafting. Preoperative diabetes mellitus was a predictor of in-hospital mortality.

Relationship of immunosuppression and serum lipids to the development of coronary arterial disease in the transplanted heart.

Coronary arterial disease in the cardiac allograft has emerged as the most serious long term complication of cardiac transplantation. The influence of patient-related and other potential risk factors on the development of coronary arterial disease at 1 year subsequent to cardiac transplantation was examined in 207 recipients. The mean age of donors in patients with coronary arterial disease was 28.5 +/- 9.5 years, compared to 22.6 +/- 7.9 years in patients without coronary arterial disease (P less than 0.01). Eight of the 35 patients who received immunosuppression by means of prednisone and azathioprine developed coronary arterial disease compared to 5 of the 172 patients who were treated with cyclosporin and azathioprine without routine oral prednisone (P less than 0.01). The relationship of levels of serum lipids to the subsequent development of coronary arterial disease was investigated in 95 patients with angiographically normal coronary arteries one year after cardiac transplantation. The cumulative probability of coronary arterial disease in those with total cholesterol greater than 5.8 mmol/l was 9.3% at 2 years (n = 40), 24.4% at 4 years (n = 21) and 45% at 4 years (n = 9) compared with 4.3% at 2 years (n = 45), 7.4% at 3 years (n = 32) and 14% at 4 years (n = 14) in those with a total cholesterol less than 5.8 mmol/l (P less than 0.05). Similarly, the incidence of coronary arterial disease was increased in patients with serum triglyceride greater than 1.4 mmol/l (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cerivastatin on vascular function of human radial and left internal thoracic arteries

BACKGROUND Statins may enhance vascular function independently of effects on cholesterol. This study investigated the ability of statins to modulate the vascular recovery of arteries used as coronary bypass grafts. METHODS Specimens of radial artery and left internal thoracic artery were obtained during coronary artery bypass grafting. The specimens were divided into vascular rings, which were incubated in the absence or presence of cerivastatin (10(-6) mol/L) for either 2 or 24 hours. Using an organ bath technique, endothelial function was examined using acetylcholine (10(-9) to 10(-5) mol/L) after contraction by 3x10(-8) mol/L of endothelin-1. RESULTS Time-related endothelial dysfunction was shown in the control group of radial artery but not in the cerivastatin group: maximal endothelium-dependent vasodilation in the control and cerivastatin groups were 56.8% +/- 10.2% and 65.9% +/- 10.1% at 2 hours and 39.4% +/- 4.7% and 68.4% +/- 5.0% (p < 0.01, vs control) at 24 hours, respectively. On the other hand, in the left internal thoracic artery, those in the control and cerivastatin groups were 38.3% +/- 8.2% and 45.0% +/- 5.5% at 2 hours and 38.1% +/- 8.2% and 56.5% +/- 8.8% at 24 hours, respectively (NS). CONCLUSIONS In radial artery, cerivastatin significantly preserved endothelium-dependent vasodilation, which diminished with time in the control group. This could have very important implications in the clinical practice of coronary artery bypass grafting.

Ultrafast computed tomographic scanning for detection of coronary disease in cardiac transplant recipients.

Abstract Coronary calcification detected by ultrafast CT scanning correlates well with angiographic disease, with a negative predictive value (with respect to coronary angiography) of up to 97%, which may make ultrafast CT scanning a useful tool for screening cardiac transplant recipients for coronary disease.