Haematological Drugs Affecting Lipid Metabolism and Vascular Health.

Many drugs affect lipid metabolism and have side effects which promote atherosclerosis. The prevalence of cancer-therapy-related cardiovascular (CV) disease is increasing due to development of new drugs and improved survival of patients: cardio-oncology is a new field of interest and research. Moreover, drugs used in transplanted patients frequently have metabolic implications. Increasingly, internists, lipidologists, and angiologists are being consulted by haematologists for side effects on metabolism (especially lipid metabolism) and arterial circulation caused by drugs used in haematology. The purpose of this article is to review the main drugs used in haematology with side effects on lipid metabolism and atherosclerosis, detailing their mechanisms of action and suggesting the most effective therapies.

Carotid Atherosclerosis, Ultrasound and Lipoproteins.

Carotid artery plaques are considered a measure of atherosclerosis and are associated with an increased risk of atherosclerotic cardiovascular disease, particularly ischemic strokes. Monitoring of patients with an elevated risk of stroke is critical in developing better prevention strategies. Non-invasive imaging allows us to directly see atherosclerosis in vessels and many features that are related to plaque vulnerability. A large body of evidence has demonstrated a strong correlation between some lipid parameters and carotid atherosclerosis. In this article, we review the relationship between lipids and atherosclerosis with a focus on carotid ultrasound, the most common method to estimate atherosclerotic load.

Association between Non-HDL-C/HDL-C Ratio and Carotid Intima-Media Thickness in Post-Menopausal Women.

Atherogenic lipoproteins (particularly, very low-density lipoproteins, VLDL) are associated with subclinical atherosclerosis. The present study aims at evaluating whether routinely analysed lipid parameters are associated with carotid intima-media thickness, a proxy for subclinical atherosclerosis. Lipid parameters from 220 post-menopausal women undergoing ultrasound investigation of the carotid arteries were analysed. Forty-five percent of women showed subclinical atherosclerosis on carotid ultrasound. The mean carotid intima-media thickness was 1.26 ± 0.38 mm. The mean value of the non-HDL-C/HDL-C ratio was 3.1 ± 1.2. Univariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima-media thickness (r = 0.21, p = 0.001). After adjusting for cardiovascular risk factors (age, systolic blood pressure, smoking, body mass index Homeostasis model assessment: insulin resistance and high-sensitivity C-Reactive-Protein), multivariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima-media thickness (ß = 0.039, p = 0.04). Logistic regression analysis showed that the highest tertile of the non-HDL-C/HDL-C ratio was associated with the presence of carotid plaques (OR = 3.47, p = 0.003). Finally, a strong correlation between non-HDL-C/HDL-C ratio and cholesterol bound to VLDL (r = 0.77, p < 0.001) has been found. Non-HDL-C/HDL-C ratio is associated with the presence of carotid atherosclerosis in post-menopausal women and is strongly correlated to VLDL-C levels.

Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels.

BACKGROUND: atherosclerotic process inexorably advances in patients reaching low-density lipoprotein cholesterol (LDL-C) targets. An attractive hypothesis is that lipoprotein particles (very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL)), could contribute to residual risk. The present study aims to investigate the relationship between carotid intima-media thickness (IMT) and different lipoprotein subfractions in a cohort of healthy postmenopausal women. METHODS: 75 postmenopausal women, at LDL-C target levels without overt cardiovascular disease, underwent biochemical analyses (including subfraction assay of plasma lipoproteins) and carotid ultrasound examination. RESULTS: a statistically significant correlation between VLDL and carotid IMT (p < 0.001) was found. No significant correlation was found between carotid IMT and LDL-C (p = 0.179), IDL-C (p = 0.815), high-density lipoprotein (HDL) (p = 0.855), and LDL score (p = 0.240). Moreover, IMT is significantly correlated to LDL particle diameter (p = 0.044). After adjusting for age, systolic blood pressure, body mass index, smoking habits, glucose plasma concentration, and Lipoprotein(a) (Lpa) levels, multivariate analysis showed that women in the third tertile of VLDL-C, compared with those in the first tertile, were significantly associated to the highest IMT (p = 0.04). CONCLUSIONS: in this cohort of postmenopausal women, VLDL-C was significantly associated to carotid IMT, independent of main cardiovascular risk factors. These findings pave the way for targeting circulating concentrations of VLDL-C to reduce cardiovascular events in patients with target LDL-C levels.

Atherogenic Lipoprotein Subfractions and Carotid Atherosclerosis in Menopausal Women.

The aim of the study was to evaluate the relationship between cholesterol contained in very-low-density lipoproteins (VLDL-C), intermediate-density lipoproteins (IDL-C), low-density lipoproteins, high-density lipoproteins, and carotid intima-media thickness (cIMT) and carotid plaques in 228 postmenopausal women (63.1 ± 8.2 years) who participated in the ATENA Project and underwent clinical, biochemical (including the assay of lipoproteins using the Lipoprint system), and carotid ultrasound tests. Very-low-density lipoprotein cholesterol had a statistically significant linear association with cIMT ( P < .001), which remained significant after adjustment for age, smoking, systolic blood pressure, glucose, and body mass index ( r2 = .20, P < .05). Higher concentrations of IDL-C and cholesterol contained in triglyceride-rich lipoproteins (TRL-C, ie, VLDL-C + IDL-C) were associated with plaques in the common carotid (tertile III/tertile I: odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.21-5.32, P < .02; OR = 2.30, 95% CI = 1.05-5.01, P < .05, respectively), after adjustment for main cardiovascular risk factors. In conclusion, high concentrations of VLDL-C and TRL-C are independently associated with the presence of carotid plaques. Their assay represents a useful tool for improving our knowledge on the role of different classes of lipoproteins in atherosclerosis.

Carotid artery diameter and wall stiffness in proteinuric renal disease without severely reduced kidney function.

PURPOSE: To evaluate the carotid artery diameter, and wall thickness and stiffness in patients with glomerulopathy and proteinuria without severely reduced kidney function. METHODS: We compared 30 control subjects to 30 patients with glomerular disease, proteinuria, and glomerular filtration rate > 30 ml/min/1.73 m(2) : membranous glomerulonephritis (n = 13), minimal change disease (n = 2), focal and segmental glomerulosclerosis (n = 3), IgA nephropathy (n = 5), lupus nephritis (n = 5), antiphospholipid antibody nephropathy (n = 1), cryoglobulinemic glomerulonephritis (n = 1). The laboratory evaluations included carotid artery diameter, intima-media thickness, and stiffness measurements. RESULTS: Carotid cross-sectional area of intima-media complex was thicker in patients (18.6 ± 1.4 [x ± SEM]) than in controls (14.8 ± 0.6 mm(2) , p = 0.014), as was carotid artery wall stiffness (8.96 ± 0.86 versus 5.65 ± 0.38, [x ± SEM], p < 0.01). This difference remained significant after adjustment for age, sex, and metabolic cardiovascular risk factors: carotid stiffness was 9.19 ± 0.67 (99% confidence interval [CI] 7.40-10.98)] in patients and 4.80 ± 0.75 (99% CI 2.79-7.11) in controls; adjusted mean difference 4.40 (99% CI 1.46-7.34); p <0.001. CONCLUSIONS: This study showed, for the first time, signs of altered structural and elastic properties of the arterial wall in patients with proteinuria and glomerular disease without severely reduced kidney function.

Relation of body mass index with carotid intima-media thickness and diameter is independent of metabolic syndrome in postmenopausal Mediterranean women.

OBJECTIVE: The aim of this study was to evaluate whether overweight and obesity are associated with arterial abnormalities in postmenopausal women and the contribution of the metabolic syndrome. METHODS: A total of 390 postmenopausal women (mean age, 63.1 ± 7.7 y) living in the metropolitan area of Naples, Southern Italy, and participating in a population-based cohort study (Progetto Atena) were offered an ultrasound examination of the carotid arteries; 370 women accepted. Blood pressure, serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting glucose, insulin, apolipoprotein B, and high-sensitivity C-reactive protein were measured in all participants. RESULTS: Women in the second and third tertiles of body mass index showed a greater common carotid intima-media thickness compared with those in the first tertile (tertile II vs I, odds ratio, 2.15; P = 0.013; tertile III vs I, odds ratio, 2.24; P = 0.018), adjusted for age and metabolic syndrome. Obese and overweight postmenopausal women showed greater common carotid lumen diameters as compared with lean postmenopausal women (mean ± SD, 6.36 ± 0.86, 6.16 ± 0.65, and 5.96 ± 0.59 mm, respectively; P < 0.001 [obese vs lean] and P = 0.04 [overweight vs lean]); no statistical difference in carotid lumen diameter was found between obese and overweight postmenopausal women. The statistical significance between obese and lean postmenopausal women was retained even after adding the components of the metabolic syndrome as covariates. CONCLUSIONS: These findings indicate an association between overweight, obesity, and preclinical carotid artery abnormalities, independently of the metabolic syndrome, in a population of postmenopausal women.

Comparison of two diets of varying glycemic index on carotid subclinical atherosclerosis in obese children.

Childhood obesity is associated with an increased carotid intima-media thickness (IMT) and stiffness. Increased carotid wall thickening and rigidity are considered markers of subclinical atherosclerosis. The aim of the present study was to test the effect of two hypocaloric diets of varying glycemic index on weight loss and markers of subclinical atherosclerosis in obese children. Seventy consecutive obese children attending the Outpatient Weight Clinic of the Department of Pediatrics were invited to participate in an intensive dietary protocol. Twenty-six accepted and were randomly assigned to two different groups: the first group followed a hypocaloric low-glycemic index diet and the second a hypocaloric high-glycemic index diet. Anthropometric measures and biochemical tests were performed in all children. Quantitative B-mode ultrasound scans were used to measure intima-media thickness (IMT) and diameters of the common carotid artery. Considering both groups together, at 6 months, body mass index decreased from 28.3 +/- 3.1 to 25.8 +/- 3.3 kg/m(2), systolic blood pressure from 119 +/- 12 to 110 +/- 11 mmHg (P< 0.001), diastolic blood pressure from 78 +/- 8 to 74 +/- 7 mmHg (P< 0.001), IMT from 0.48 +/- 0.05 to 0.43 +/- 0.07 mm (P< 0.001), stiffness from 3.57 +/- 1.04 to 2.98 +/- 0.94 mm (P = 0.002), and high-sensitivity C-reactive protein from 1.5 +/- 0.9 (values log transformed) to 0.4 +/- 1.1 (P < 0.001). No differences were detectable in fasting serum triglycerides, total cholesterol, and high-density lipoprotein cholesterol. Insulin resistance (calculated by the HOmeostatic Model Assessment index [HOMA] score) significantly reduced only in the low-glycemic-index diet group (P < 0.04). In conclusion, this study confirms a benefit of hypocaloric diets on carotid IMT and stiffness in obese children and demonstrates, for the first time, an amelioration of insulin sensitivity in obese children after a low-glycemic index diet. These results justify the advice to obese children to follow a low-glycemic index diet in order to improve their cardiometabolic profile.

Dietary and circulating antioxidant vitamins in relation to carotid plaques in middle-aged women.

BACKGROUND: The results of the few studies conducted on the relation between antioxidant vitamins and carotid atherosclerosis have been inconclusive. OBJECTIVE: We evaluated the association between preclinical carotid atherosclerosis, as determined by high-resolution B-mode ultrasound, and both the intake amounts and plasma concentrations of antioxidant vitamins. DESIGN: Among 5062 participants in Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in women, 310 women were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis. The participants answered a food-frequency questionnaire, and their plasma concentrations of vitamin E, vitamin A, and carotenoids were measured. None of the women took vitamin supplements. RESULTS: The occurrence of atherosclerotic plaques at the carotid bifurcation was inversely associated with tertiles of vitamin E intake; the test for a linear trend across tertiles was significant (P < 0.05). Similarly, the ratio of plasma vitamin E to plasma cholesterol was inversely related to the presence of plaques at the carotid bifurcation; the test for a linear trend across tertiles was significant (P < 0.02). No association was found between the intake of other antioxidant vitamins (vitamins A and C and carotenoids) or their plasma concentrations and the presence of carotid plaques. CONCLUSIONS: An inverse association was found between both the intake amount and plasma concentration of vitamin E and preclinical carotid atherosclerosis in middle-aged women. This association was independent of other cardiovascular risk factors, was not related to vitamin supplements, and supports the hypothesis that low vitamin E intake is a risk factor for early atherosclerosis.

Association of impaired glucose homeostasis with preclinical carotid atherosclerosis in women: Impact of the new American Diabetes Association criteria.

The aim of this study was to determine whether impaired glucose regulation, defined according to the new American Diabetes Association (ADA) criteria, is associated with early signs of carotid atherosclerosis. We examined 310 clinically healthy women from southern Italy, aged 30 to 69 years, recruited for a prospective study, currently ongoing, on the etiology of cardiovascular disease and cancer in the female population (Progetto Atena). All subjects underwent cardiovascular risk factor assessment and high resolution B-mode ultrasound to measure intima-media thickness (IMT) of common carotid arteries and carotid bifurcations. At the time of our survey, fasting glucose levels > or = 7.0 mmol/L had already been found in 7 women, 17 participants were diagnosed on that occasion as having new diabetes, 38 had impaired fasting glucose (IFG), and the remaining 248 presented normal fasting glucose values (NFG). Diabetic women showed a worse cardiovascular risk profile, with higher values of triglycerides, body mass index, and diastolic blood pressure than either normoglycemic or IFG subjects. The frequency of atherosclerotic plaques (IMT > 1.2 mm) increased as glucose homeostasis worsened. In multivariate logistic regression analyses, only diabetes mellitus was associated with a significantly increased risk of carotid atherosclerosis (odds ratio [OR], 11.5; 95% confidence interval [CI], 1.4 to 92.7). Our findings suggest a definite association between diabetes mellitus, as defined by the new ADA diagnostic criteria and early carotid structural changes. Furthermore, the condition of IFG does not seem to identify subjects at significantly increased atherosclerotic risk.