Effect of statins on LDL particle size in patients with familial combined hyperlipidemia: a comparison between atorvastatin and pravastatin

Sirtori, Cesare R.; Calabresi, Laura; Pisciotta, Livia; Cattin, Luigi; Pauciullo, Paolo; Montagnani, M; Manzato, Enzo; Bon, Gabriele Bittolo; Fellin, Renato

doi:10.1016/j.numecd.2004.08.001

Cited by 35 publications

(14 citation statements)

References 36 publications

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“…Diabetic patients who take metformin are patients with more severe diabetes who need pharmacological therapy. In patients with insulin-resistant diabetes treated with metformin, there is the so-called atherogenic dyslipidemia, characterized by fasting hypertriglyceridemia, which is usually associated with low levels of HDL cholesterol and high levels of small and dense LDL particles (24). In our study, the values of total and HDL cholesterol was higher in patients without DM2 taking ASA, while glucose and triglycerides were higher in DM2 patients not on ASA treatment.…”

Section: Discussionsupporting

confidence: 46%

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients

et al. 2018

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Abstract. Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non-diabetic patients, have an inhibitory effect on cancer cell survival. The present population-based study conducted in the province of Trieste (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients. All permanent residents diagnosed with a CRC between 2004 and 2007 were ascertained through the regional health information system. CRC-specific and relative survival probabilities were computed for each group of patients defined by CRC stage, presence or absence of DM2 treated with metformin, and presence or absence of daily ASA therapy. A total of 515 CRC patients without DM2 and 156 with DM2 treated with metformin were enrolled in the study. At the time of CRC diagnosis, 71 (14%) nondiabetic and 39 (25%) diabetic patients were taking ASA daily. The five-year relative survival for stage III CRC was 101% [95% confidence interval (CI) =76-126] in the 18 patients with DM2 treated with metformin and ASA, 55% (95% CI=31-78) in the 23 without DM2 treated with ASA, 55% (95% CI=45-65) in the 150 without DM2 not taking ASA, and 29% (95% CI=13-45) in the 43 with DM2 treated with metformin, however not with ASA. The findings support the hypothesis of a possible inhibitory effect of metformin and ASA on CRC cells. Randomized controlled trials are required to verify this hypothesis.

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Section: Discussionsupporting

confidence: 46%

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients

et al. 2018

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“…Treatment with pravastatin favorably altered the LDL size in three studies [13][14][15], but in many others did not [16][17][18][19][20][21][22][23][24][25][26] (Table 1). In sixty-five patients with low HDL levels and hypertriglyceridemia, the combination of pravastatin and niacin resulted in significant improvements of small, dense LDL, whereas pravastatin alone or in combination with magnesium did not [13].…”

Section: Pravastatinmentioning

confidence: 99%

“…Besides these three reports, 11 studies have showed that pravastatin is not able to significant increase LDL size or to reduce small, dense LDL [16][17][18][19][20][21][22][23][24][25][26]. This has been confirmed at different doses of pravastatin and in different categories of patients: with primary hypercholesterolaemia [16,22], with type IIa dyslipidemia [17,23], with combined [18,19] or familial combined hyperlipidemia [20,26], with heterozygous familial hypercholesterolemia [21], with type 2 diabetes [25], suggesting a very limited role of this drug in modifying LDL peak particle size and their subclasses.…”

Section: Pravastatinmentioning

confidence: 99%

The Clinical Relevance of Low-Density-Lipoproteins Size Modulation by Statins

Rizzo

Berneis

2006

Cardiovasc Drugs Ther

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The predominance of small, dense low density lipoproteins (LDL) has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III; in fact, LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart disease. Several studies have also shown that the therapeutical modulation of LDL size is of great benefit in reducing the risk of cardiovascular events. Hypolipidemic treatment is able to alter LDL subclass distribution and statins are currently the most widely used lipid-lowering agents. Statins are potent inhibitors of hydroxy-methyl-glutaryl-coenzyme A reductase, the rate-limiting enzyme in hepatic cholesterol synthesis and are the main drugs of choice for the treatment of elevated plasma LDL cholesterol concentrations. Statins potentially lower all LDL subclasses (e.g., large, medium and small particles); thus, their net effect on LDL subclasses or size is often only moderate. However, a strong variation has been noticed among the different agents: analyses of all published studies suggest a very limited role of pravastatin and simvastatin in modifying LDL size and their subclasses, while fluvastatin and atorvastatin seem to be much more effective agents. Finally, rosuvastatin, the latest statin molecule introduced in the market, seems to be promising in altering LDL subclasses towards less atherogenic particles.

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“…It has been reported that mean LDL particle size was increased by treatment with atrovastatin and decreased by treatment with pravastatin in patients with familial hyperlipidemia. 29 Recently, we reported that highly purified eicosapentaenoic acid reduced levels of sd-LDL-C, detected with a LipoPrint LDL system, remnants and CRP in patients with MS. 30 There is a need to further discuss the best use of diet, exercise and various pharmacological agents to reduce the risk of CVD in patients with MS.…”

Section: Discussionmentioning

confidence: 97%

Small Dense LDL-Cholesterol Relative to LDL-Cholesterol is a Strong Independent Determinant of Hypoadiponectinemia in Metabolic Syndrome

Satoh

Wada

Ono

et al. 2008

Circ J

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etabolic syndrome (MS) is a cluster of multiple atherosclerotic risk factors including glucose intolerance, dyslipidemia, hypertension and visceral obesity. 1 Results from a large population-based study demonstrated that the presence of MS is associated with a high risk of all-cause mortality and cardiovascular morbidity and mortality, regardless of variations in definition of MS. 2,3 Dyslipidemia in MS is characterized by an increase in triglyceride levels and decrease in high-density lipoprotein (HDL)-cholesterol (C) levels. 4 Despite the fact that lowdensity lipoprotein (LDL)-C is a sensitive indicator of risk for developing cardiovascular disease (CVD) in the general population and the primary target of lipid-modulating therapy, 5 LDL-C is not included in any of the criteria for MS. 1 To date, a useful and convenient method of predicting CVD in individuals with MS has not been established.Because the synthesis and degradation of lipoproteins are dependent on insulin action, it has been suggested that the size and composition of lipoproteins are related to insulin resistance, a hallmark of MS. Small dense LDL (sd-LDL) particles stay in the blood for longer and are more susceptible to oxidative modification than medium-sized or large LDL particles. 6 Therefore, sd-LDL particles are easily oxidized and engulfed by macrophages through injured endothelial cells, resulting in the formation of atherosclerotic lesions. 7 In clinically healthy middle-aged men in the general population, previous studies have demonstrated that MS is associated with not only a decrease in adiponectin levels and increase in intima-media thickness of carotid arteries but also a reduction of LDL particle size. 8,9 However, there has been no cross-sectional or longitudinal study that precisely analyzes correlations of sd-LDL with MS variables. Furthermore, the small size of the LDL particle does not always accompany an increase in sd-LDL mass. 10 It has been suggested that the amount of sd-LDL-C serves as a more sensitive predictor of CVD than LDL-particle size. 10 Therefore, we investigated the actual quantities of sd-LDL-C in patients with MS and their association with MS variables. The present study has examined circulating levels of sd-LDL-C in outpatients in our hospital and the association of these levels with various parameters of MS, including levels of adipocyte-derived cytokines (adipocytokines). Furthermore, we examined the effects of a long period of weight reduction therapy through diet and exercise on these levels in obese patients. Small Dense LDL-Cholesterol Relative to LDL-Cholesterol is a Strong Independent Determinant of Hypoadiponectinemia in Metabolic SyndromeNoriko Satoh, MD; Hiromichi Wada, MD*; Koh Ono, MD*; Hajime Yamakage; Kazunori Yamada, MD**; Tameo Nakano, MD † ; Masakazu Hattori, MD; Akira Shimatsu, MD; Hideshi Kuzuya, MD**; Koji Hasegawa, MD* Background Small dense low-density lipoprotein (sd-LDL) is an atherogenic lipoprotein closely associated with an increased risk of cardiovascular diseases. However, a pr...

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Effect of statins on LDL particle size in patients with familial combined hyperlipidemia: a comparison between atorvastatin and pravastatin

Cited by 35 publications

References 36 publications

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients

The Clinical Relevance of Low-Density-Lipoproteins Size Modulation by Statins

Small Dense LDL-Cholesterol Relative to LDL-Cholesterol is a Strong Independent Determinant of Hypoadiponectinemia in Metabolic Syndrome

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