Personalized medicine in lipid-modifying therapy.

The choice of lipid-modifying treatment is largely based on the absolute level of cardiovascular risk and baseline lipid profile. Statins are the first-line treatment for most patients requiring reduction of low-density-lipoprotein cholesterol (LDL-C) and ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors can be added to reach LDL-C targets. Statins have some adverse effects that are somewhat predictable based on phenotypic and genetic factors. Fibrates or omega-3 fatty acids can be added if triglyceride levels remain elevated. The RNA-targeted therapeutics in development offer the possibility of selective liver targeting for specific lipoproteins such as lipoprotein(a) and long-term reduction of LDL-C with infrequent administration of a small-interfering RNA may help to overcome the problem of adherence to therapy.

The effects of coenzyme Q10 supplementation on lipid profiles among patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic inflammation and increased oxidative stress significantly contribute in developing coronary artery disease (CAD). Hence, antioxidant supplementation might be an appropriate approach to decrease the incidence of CAD. This systematic review and meta-analysis was aimed to determine the effects of coenzyme Q10 (CoQ10) supplementation on lipid profile, as one of the major triggers for CAD, among patients diagnosed with coronary artery disease. METHODS: EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science were searched for studies prior to May 20th, 2018. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. I-square and Q-tests were used to measure the existing heterogeneity across included studies. Considering heterogeneity among studies, fixed- or random-effect models were applied to pool standardized mean differences (SMD) as overall effect size. RESULTS: A total of eight trials (267 participants in the intervention group and 259 in placebo group) were included in the current meta-analysis. The findings showed that taking CoQ10 by patients with CAD significantly decreased total-cholesterol (SMD -1.07; 95% CI, - 1.94, - 0.21, P = 0.01) and increased HDL-cholesterol levels (SMD 1.30; 95% CI, 0.20, 2.41, P = 0.02). We found no significant effects of CoQ10 supplementation on LDL-cholesterol (SMD -0.37; 95% CI, - 0.87, 0.13, P = 0.14), lipoprotein (a) [Lp(a)] levels (SMD -1.12; 95% CI, - 2.84, 0.61, P = 0.20) and triglycerides levels (SMD 0.01; 95% CI, - 0.22, 0.24, P = 0.94). CONCLUSIONS: This meta-analysis demonstrated the promising effects of CoQ10 supplementation on lowering lipid levels among patients with CAD, though it did not affect triglycerides, LDL-cholesterol and Lp(a) levels.

Effects of omega-3 fatty acids on serum lipids, lipoprotein (a), and hematologic factors in hemodialysis patients.

BACKGROUND: Lipid abnormalities, especially high serum lipoprotein (a) [Lp (a)] concentration, and anemia are two major causes of cardiovascular diseases (CVDs) in hemodialysis patients. Therefore, this study was designed to investigate the effects of marine omega-3 fatty acids on serum lipids, Lp (a), and hematologic factors in hemodialysis patients. METHODS: Thirty-four hemodialysis patients were randomly assigned to either omega-3 fatty acid supplement or placebo group. Patients in the omega-3 fatty acids group received 2080 mg marine omega-3 fatty acids, daily for 10 weeks, whereas the placebo group received a corresponding placebo. At baseline and the end of week 10, 7 mL blood was collected after a 12- to 14-h fast and serum triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lp (a), blood hemoglobin, hematocrit, red blood cells (RBCs), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were measured. RESULTS: Serum triglyceride decreased significantly in the omega-3 fatty acids group at the end of week 10 compared with baseline (p < 0.05) and this reduction was significant in comparison with the placebo group (p < 0.01). No significant differences were observed between the two groups in mean changes of serum total cholesterol, LDL-C, HDL-C, Lp (a), blood hemoglobin, hematocrit, RBC, MCV, MCH, and MCHC. CONCLUSION: The results of our study indicate that marine omega-3 fatty acids can reduce serum triglyceride, as a risk factor for CVD, but it does not affect other serum lipids, Lp (a), and hematologic factors in hemodialysis patients.

The effects of low dose n-3 fatty acids on serum lipid profiles and insulin resistance of the elderly: a randomized controlled clinical trial.

INTRODUCTION: N-3 fatty acids have several beneficial effects on dyslipidemia and diabetes, conditions which are prevalent in the elderly. This study assessed the effects of low-dose n-3 fatty acids on serum lipid profile, lipoprotein(a), apolipoprotein B, fasting glucose, insulin, and insulin resistance in a group of elderly Iranians. MATERIALS AND METHODS: A 6-month randomized, double-blind placebo-controlled clinical trial was carried out in 124 elderly residents of Kahrizak Charity Foundation aged >or= 65. The intervention group was supplemented with 1 g/day fish oil capsule (with 180 mg eicosapentaenoic acid, EPA; and 120 mg docosahexaenoic acid, DHA; a total of 300 mg n-3 fatty acids as effective constituents). Fasting blood samples were collected at baseline and after 6 months of the trial. RESULTS: There were no significant effects of fish oil on the studied variables in the intervention group. In the placebo group, serum triglyceride significantly increased and high-density lipoprotein cholesterol significantly decreased (p = 0.01 and p = 0.009, respectively). By repeated measurement analysis after adjustments, the overall decrease in serum triglycerides compared with placebo was significant (p = 0.04). CONCLUSION: Supplementation with low dose n-3 fatty acids for 6 months could significantly protect elderly Iranians from a rise in serum triglycerides.

Novel soybean oils with different fatty acid profiles alter cardiovascular disease risk factors in moderately hyperlipidemic subjects.

BACKGROUND: A variety of soybean oils were developed with improved oxidative stability and functional characteristics for use as alternatives to partially hydrogenated fat. OBJECTIVE: The objective was to assess the effect of selectively bred and genetically modified soybean oils with altered fatty acid profiles, relative to common soybean and partially hydrogenated soybean oils, on cardiovascular disease risk factors. DESIGN: Thirty subjects (16 women and 14 men) aged >50 y with LDL-cholesterol concentrations >130 mg/dL at screening consumed 5 experimental diets in random order for 35 d each. Diets contained the same foods and provided 30% of energy as fat, of which two-thirds was either soybean oil (SO), low-saturated fatty acid soybean oil (LoSFA-SO), high-oleic acid soybean oil (HiOleic-SO), low-alpha-linolenic acid soybean oil (LoALA-SO), or partially hydrogenated soybean oil (Hydrog-SO). RESULTS: Plasma phospholipid patterns reflected the predominant fat in the diet. LDL-cholesterol concentrations were 3.66 +/- 0.67(b), 3.53 +/- 0.77(b), 3.70 +/- 0.66(b), 3.71 +/- 0.64(a,b), and 3.92 +/- 0.70(a) mol/L; HDL-cholesterol concentrations were 1.32 +/- 0.32(a,b), 1.32 +/- 0.35(b), 1.36 +/- 0.33(a), 1.32 +/- 0.33(b), and 1.32 +/- 0.32(a,b) mol/L for the SO, LoSFA-SO, HiOleic-SO, LoALA-SO, and Hydrog-SO diets, respectively (values with different superscript letters are significantly different, P < 0.05). No significant effects were observed on VLDL-cholesterol, triacylglycerol, lipoprotein(a), and C-reactive protein concentrations or on ratios of LDL cholesterol to apolipoprotein B (apo B) and HDL cholesterol to apo A-I. Total cholesterol:HDL cholesterol was lower after subjects consumed the unhydrogenated soybean oils than after they consumed the Hydrog-SO diet. CONCLUSIONS: All varieties of soybean oils resulted in more favorable lipoprotein profiles than did the partially hydrogenated form. These soybean oils may provide a viable option for reformulation of products to reduce the content of trans fatty acids.

Palm and partially hydrogenated soybean oils adversely alter lipoprotein profiles compared with soybean and canola oils in moderately hyperlipidemic subjects.

BACKGROUND: Partially hydrogenated fat has an unfavorable effect on cardiovascular disease risk. Palm oil is a potential substitute because of favorable physical characteristics. OBJECTIVE: We assessed the effect of palm oil on lipoprotein profiles compared with the effects of both partially hydrogenated fat and oils high in monounsaturated or polyunsaturated fatty acids. DESIGN: Fifteen volunteers aged > or =50 y with LDL cholesterol > or =130 mg/dL were provided with food for each of 4 diets (35 d/phase) varying in type of fat (partially hydrogenated soybean, soybean, palm, or canola; two-thirds fat, 20% of energy). Plasma fatty acid profiles, lipids, lipoproteins, apolipoprotein A-I, apolipoprotein B, lipoprotein(a), glucose, insulin, HDL subfractions, and indicators of lipoprotein metabolism (HDL-cholesterol fractional esterification rate, cholesteryl ester transfer protein, phospholipid transfer protein, and paraoxonase activities) were measured at the end of each phase. RESULTS: Plasma fatty acid profiles reflected the main source of dietary fat. Partially hydrogenated soybean and palm oils resulted in higher LDL-cholesterol concentrations than did soybean (12% and 14%, respectively; P < 0.05) and canola (16% and 18%; P < 0.05) oils. Apolipoprotein B (P < 0.05) and A-I (P < 0.05) concentrations mirrored the pattern of LDL- and HDL-cholesterol concentrations, respectively. No significant effect on the total-to-HDL cholesterol ratio was observed for palm oil compared with the other dietary fats. HDL3 cholesterol was higher after palm oil than after partially hydrogenated and soybean oils (P < 0.05). Differences in measures of glucose and HDL intravascular processing attributable to dietary fat were small. CONCLUSION: Palm and partially hydrogenated soybean oils, compared with soybean and canola oils, adversely altered the lipoprotein profile in moderately hyperlipidemic subjects without significantly affecting HDL intravascular processing markers.

Alcohol-extracted, but not intact, dietary soy protein lowers lipoprotein(a) markedly.

We previously found that dietary soy protein produces higher lipoprotein(a) [Lp(a)] plasma concentrations than does casein. This study tested the hypothesis that soy protein contains Lp(a)-raising alcohol-removable components. Twelve normolipidemic women and men consumed, in a crossover design, liquid-formula diets containing casein, soy protein, or alcohol-extracted soy protein. Dietary periods of 32 days were separated by washout periods on self-selected diets. Fasting lipid and Lp(a) levels were measured throughout. Median Lp(a) concentration was >2-fold greater after 28 to 32 days on a soy protein diet than after an extracted soy protein diet (P<0.001). Lp(a) concentrations after casein and extracted soy protein diets were virtually identical. Women and men responded similarly. When the switch was made from a self-selected to a soy protein diet, median Lp(a) concentration increased 16% after 1 week (P<0.01) and subsequently decreased toward baseline; extracted soy protein and casein diets never exhibited increased median Lp(a) levels, and after 28 to 32 days, these levels were decreased >60% below baseline (P<0.001 and P<0.01, respectively). Low density lipoprotein cholesterol concentrations were not different after the 3 experimental diets. The data indicate that (1) dietary soy protein can increase Lp(a) concentrations, (2) this effect is eliminated after alcohol extraction, and (3) high Lp(a) concentrations may be markedly reduced by diet.

Replacement of partially hydrogenated soybean oil by palm oil in margarine without unfavorable effects on serum lipoproteins.

We have compared the effects of three different margarines, one based on palm oil (PALM-margarine), one based on partially hydrogenated soybean oil (TRANS-margarine) and one with a high content of polyunsaturated fatty acids (PUFA-margarine), on serum lipids in 27 young women. The main purpose of the study was to test if replacement of trans fatty acids in margarine by palmitic acid results in unfavorable effects on serum lipids. The sum of saturated fatty acids (12:0, 14:0, 16:0) was 36.3% of total fatty acids in the PALM-diet, the same as the sum of saturated (12:0, 14:0, 16:0) (12.5%) and trans (23.1%) fatty acids in the TRANS-diet. This sum was 20.7% in the PUFA-diet. The content of oleic acid was 37.9, 35.2, and 38.6%, respectively, in the three diets, whereas linoleic acid amounted to 16, 13.5, and 27.3%, respectively. Total fat provided 30-31% and the test margarines 26% of total energy in all three diets. The subjects consumed each of the diets for 17 d in a Latin-square crossover design. There were no significant differences in total cholesterol, low density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB) between the TRANS- and the PALM-diets. High density lipoprotein (HDL)-cholesterol and apoA-1 were significantly higher on the PALM-diet compared to the TRANS-diet whereas the ratio of LDL-cholesterol to HDL-cholesterol was lower, although not significantly (P = 0.077) on the PALM-diet. Total cholesterol, LDL-cholesterol, and apoB were significantly lower on the PUFA-diet compared to the two other diets. HDL-cholesterol was not different on the PALM- and the PUFA-diets but it was significantly lower on the TRANS-diet compared to the PUFA diet. Compared to the PUFA-diet the ratio of LDL- to HDL-cholesterol was higher on both the PALM- and the TRANS-diets whereas apoA-1 was not different. Triglycerides and lipoprotein (a) were not significantly different among the three diets. We concluded that nutritionally, palmitic acid from palm oil may be a reasonable alternative to trans fatty acids from partially hydrogenated soybean oil in margarine if the aim is to avoid trans fatty acids. A palm oil-based margarine is, however, less favorable than one based on a more polyunsaturated vegetable oil.

Diterpenes from coffee beans decrease serum levels of lipoprotein(a) in humans: results from four randomised controlled trials.

OBJECTIVE: Unfiltered coffee raises serum LDL cholesterol in humans, owing to the presence of the diterpenes cafestol and kahweol. Norwegians with a chronic high intake of unfiltered coffee also has elevated serum levels of lipoprotein(a), an LDL-like particle which is insensitive toward dietary interventions. We now experimentally studied the influence of coffee diterpenes on lipoprotein(a) levels. DESIGN: Four randomised controlled trials. SUBJECTS: Healthy, normolipidemic volunteers. INTERVENTIONS: Coffee, coffee oil, and pure diterpenes for 4-24 weeks. MAIN OUTCOME MEASURES: The circulating level of lipoprotein(a). RESULTS: In 22 subjects drinking five to six strong cups of cafetiere coffee per day, the median fall in lipoprotein(a) was 1.5 mg/dL after two months (P = 0.03), and 0.5 mg/dL after half a year (P > 0.05), relative to 24 filter coffee drinkers. Coffee oil doses equivalent to 10-20 cups of unfiltered coffee reduced lipoprotein(a) levels by up to 5.5 mg/dL (P < 0.05) in two separate trials (n = 12-16 per group). A purified mixture of cafestol and kahweol, as well as cafestol alone, were also effective in reducing Lp(a) levels (n = 10). Averaged over the four trials, each 10 mg/d of cafestol (plus kahweol)--the amount present in two to three cups of cafetiere coffee--decreased Lp(a) levels by 0.5 mg/dL or 4% from baseline values after four weeks (n = 63). CONCLUSIONS: Coffee diterpenes are among the few dietary exceptions shown to influence serum lipoprotein(a) levels. However, the Lp(a)-reducing potency of coffee diterpenes may subside in the long run, and their adverse side effects preclude their use as lipoprotein(a)-reducing agents.

Influence of serum lipoprotein(a) and homocyst(e)ine levels on graft patency after coronary artery bypass grafting.

High serum levels of lipoprotein(a) and homocyst(e)ine are considered independent risk factors for atherothrombotic disease. In a prospective study in patients undergoing coronary artery bypass grafting, the preoperatively determined lipoprotein(a) and homocyst(e)ine levels were related to the frequency of 1-year graft occlusion. A cohort of 610 patients who underwent coronary artery bypass surgery was followed through the first postoperative year. Shunt angiography was performed in 581 patients (95%) at a mean of 12.1 +/- 1.5 months after the operation. The serum levels of lipoprotein(a) (n = 570) and homocyst(e)ine (n = 565) in patients with occluded internal mammary artery (IMA) grafts were not significantly different from the levels in those with open IMA grafts. Also, the serum lipoprotein(a) and homocyst(e)ine levels in patients with > or = 1 occluded vein graft were not significantly different from those in patients with all vein grafts patent. This study also determined the incidence of graft occlusion in quartiles of the lipoprotein(a) and homocyst(e)ine levels, respectively, and tested for linear trends. No significant trends in the incidence of graft occlusion were found, but the number of patients with vein graft occlusions was higher in the lowest quartile of lipoprotein(a) than that in the upper 3 quartiles (odds ratio, 1.82, 95% confidence interval, 1.21 to 2.74, p = 0.0025). Controlling for background variables in multivariate models only slightly modified the results. Thus, apart from an unexplained excess of vein graft occlusions in the lowest quartile of lipoprotein(a) levels, no association between the preoperative serum lipoprotein(a) or homocyst(e)ine levels and the frequency of 1-year graft occlusion could be demonstrated.

Hormonal and biochemical profiles of premenstrual syndrome. Treatment with essential fatty acids.

Women diagnosed as suffering from premenstrual syndrome and symptom free controls were compared on hormonal parameters, glucose tolerance, mineralocorticoids, cholesterols, triglycerides, apolipoprotein (a), magnesium and calcium in the follicular and luteal phases of the menstrual cycle. The effect of treatment with essential fatty acids on the biochemical variables was also evaluated in a randomized, double-blind crossover design. The results showed that the hormonal and biochemical profiles of women with PMS and symptom free controls were markedly similar, except for aldosterone which was lower in the follicular and luteal phases and cholesterol which was higher in the follicular phase in women with PMS. No effects of treatment with essential fatty acids were found for any of the biochemical variables studied.