-
1.
HDL-C/apoA-I Ratio Is Associated with the Severity of Coronary Artery Stenosis in Diabetic Patients with Acute Coronary Syndrome.
Sun, L, Guo, M, Xu, C, Qiao, X, Hua, Y, Tuerhongjiang, G, Lou, B, Li, R, Bai, X, Zhou, J, et al
Disease markers. 2021;:6689056
Abstract
BACKGROUND Emerging evidence demonstrates that the lipid metabolism in acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) differs from nondiabetic patients. However, the distinct lipid profiles and their relationships with the severity of coronary artery stenosis and prognosis in patients with T2DM remain elusive. METHOD AND RESULT This single-center, prospective cohort study enrolled 468 patients diagnosed with ACS undergoing coronary angiography, consisting of 314 non-DM and 154 DM patients. The HDL-C/apoA-I ratio was significantly higher in DM patients with a multivessel (≥3 affected vessels) lesion than a single-vessel (1-2 affected vessels) lesion. Regression analyses showed that the HDL-C/apoA-I ratio was positively correlated to the number of stenotic coronary arteries in DM patients but not non-DM patients. However, Kaplan-Meier survival analysis revealed no significant difference in the major adverse cardiovascular event rate regarding different HDL-C/apoA-I levels in DM or non-DM ACS patients at the end of the 2-year follow-up. CONCLUSION A higher HDL-C/apoA-I ratio is associated with increased severity of coronary artery stenosis in DM patients with ACS but not with the rate of major adverse cardiovascular events at the end of the 2-year follow-up.
-
2.
Apolipoprotein A-I exchange is impaired in metabolic syndrome patients asymptomatic for diabetes and cardiovascular disease.
Borja, MS, Hammerson, B, Tang, C, Savinova, OV, Shearer, GC, Oda, MN
PloS one. 2017;(8):e0182217
Abstract
OBJECTIVE We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a measure of high-density lipoprotein (HDL) function and a key step in reverse cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients who are asymptomatic for diabetes and cardiovascular disease. We also compared HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports that CEC is enhanced in MetSyn populations. METHODS HAE and ABCA1-specific CEC were measured as tests of HDL function in 60 MetSyn patients and 14 normolipidemic control subjects. Predictors of HAE and CEC were evaluated with multiple linear regression modeling using clinical markers of MetSyn and CVD risk. RESULTS HAE was significantly reduced in MetSyn patients (49.0 ± 10.9% vs. 61.2 ± 6.1%, P < 0.0001), as was ABCA1-specific CEC (10.1 ± 1.6% vs. 12.3 ± 2.0%, P < 0.002). Multiple linear regression analysis identified apoA-I concentration as a significant positive predictor of HAE, and MetSyn patients had significantly lower HAE per mg/dL of apoA-I (P = 0.004). MetSyn status was a negative predictor of CEC, but triglyceride (TG) was a positive predictor of CEC, with MetSyn patients having higher CEC per mg/dL of TG, but lower overall CEC compared to controls. CONCLUSIONS MetSyn patients have impaired HAE that contributes to reduced capacity for ABCA1-mediated CEC. MetSyn status is inversely correlated with CEC but positively correlated with TG, which explains the contradictory results from earlier MetSyn studies focused on CEC. HAE and CEC are inhibited in MetSyn patients over a broad range of absolute apoA-I and HDL particle levels, supporting the observation that this patient population bears significant residual cardiovascular disease risk.
-
3.
Do apolipoproteins improve coronary risk prediction in subjects with metabolic syndrome? Insights from the North Italian Brianza cohort study.
Gianfagna, F, Veronesi, G, Guasti, L, Chambless, LE, Brambilla, P, Corrao, G, Mancia, G, Cesana, G, Ferrario, MM
Atherosclerosis. 2014;(1):175-81
Abstract
OBJECTIVE We assessed predictive abilities and clinical utility of CVD risk algorithms including ApoB and ApoAI among non-diabetic subjects with metabolic syndrome (MetS). METHODS Three independent population-based cohorts (3677 35-74 years old) were enrolled in Northern Italy, adopting standardized MONICA procedures. Through Cox models, we assessed the associations between lipid measures and first coronary events, as well as the changes in discrimination and reclassification (NRI) when standard lipids or apolipoproteins were added to the CVD risk algorithm including non-lipids risk factors. Finally, the best models including lipids or apolipoproteins were compared. RESULTS During the 14.5 years median follow-up time, 164 coronary events were validated. All measures showed statistically significant associations with the endpoint, while in the MetS subgroup HDL-C and ApoAI (men, HR = 1.59; 95%CI: 0.96-2.65) were not associated. Models including HDL-C plus TC and ApoB plus ApoAI for lipids and apolipoproteins, respectively, showed the best predictive values. When ApoB plus ApoAI replaced TC plus HDL-C, NRI values improved in subjects with MetS (13.8; CI95%: -5.1,53.1), significantly in those previously classified at intermediate risk (44.5; CI95% 13.8,129.6). In this subgroup, 5.5% of subjects was moved in the high (40.0% of expected events) and 17.0% in the low risk class (none had an event at 10 years). CONCLUSIONS ApoB and ApoAI could improve coronary risk prediction when used as second level biomarkers in non-diabetic subjects with MetS classified at intermediate risk. The absence of cases moved downward suggests the gain in avoiding treatments in non-cases and favor the use of apolipoproteins for risk assessment.
-
4.
Gender-specific associations of the APOA1 -75G>A polymorphism with several metabolic syndrome components in Turkish adults.
Coban, N, Onat, A, Guclu-Geyik, F, Komurcu-Bayrak, E, Can, G, Erginel-Unaltuna, N
Clinica chimica acta; international journal of clinical chemistry. 2014;:244-9
Abstract
BACKGROUND Variations in the apolipoprotein A-1 (APOA1) gene, a determinant of plasma high-density lipoprotein cholesterol (HDL-C) and apoA-I levels, may contribute to cardiovascular diseases. We evaluated the effects of a promoter polymorphism (-75G>A) in the APOA1 gene on metabolic syndrome (MetS) components in a Turkish population sample. METHODS Randomly selected 1515 Turkish adults (age 49.9±11.8 years, 785 females) were genotyped for -75G>A polymorphism using hybridization probes in Real-Time PCR LC480 device. MetS and atherogenic dyslipidemia were defined using the criteria of ATP III. RESULTS The -75AA genotype prevailed in 3.9% of men and 2.4% of women, and was independently associated with significantly higher HDL-C concentrations. Independent associations with the -75GA genotype existed only in men: higher diastolic and systolic blood pressure (BP) levels (p<0.05) were observed in male -75GA heterozygotes. Logistic regression revealed that the GA genotype confers elevated risk for atherogenic dyslipidemia (OR=1.57, 95% Cl 1.06-2.3) after adjustment for associated risk factors. Independent associations with atherogenic dyslipidemia or elevated BP did not emerge in women. CONCLUSION APOA1 -75G>A polymorphism is independently related to HDL-C concentrations. Independent associations of the -75GA genotype with elevated BP and atherogenic dyslipidemia were confined to men. These gender-modulated associations suggest novel gene-gender-environmental interactions.
-
5.
Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes).
Albers, JJ, Slee, A, O'Brien, KD, Robinson, JG, Kashyap, ML, Kwiterovich, PO, Xu, P, Marcovina, SM
Journal of the American College of Cardiology. 2013;(17):1575-9
Abstract
OBJECTIVES This study sought to examine the relationship between baseline and on-study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the development of subsequent cardiovascular (CV) events in the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) trial. BACKGROUND Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1. METHODS Individuals with CV disease and low baseline levels of high-density lipoprotein cholesterol were randomized to simvastatin plus placebo or simvastatin, plus extended-release niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both groups, to maintain an on-treatment low-density lipoprotein cholesterol in the range of 40 to 80 mg/dl. Hazard ratios (HRs) were used to evaluate the relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each treatment group. RESULTS Baseline apoB and the apoB/apoA-I ratio were significantly predictive of CV events only for the placebo group (HR: 1.17 [p = 0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on-study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25 [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and decreased Lp(a) 21%, but did not reduce CV events. CONCLUSIONS Lp(a) was associated with increased CV risk in both treatment groups indicating that it contributes to residual CV risk. However, there was no evidence that ERN reduced CV risk, despite favorable lipoprotein changes.
-
6.
FTO T/A and peroxisome proliferator-activated receptor-γ Pro12Ala polymorphisms but not ApoA1 -75 are associated with better response to lifestyle intervention in Brazilians at high cardiometabolic risk.
Curti, ML, Rogero, MM, Baltar, VT, Barros, CR, Siqueira-Catania, A, Ferreira, SR
Metabolic syndrome and related disorders. 2013;(3):169-76
Abstract
BACKGROUND The role of obesity-related polymorphisms on weight loss and inflammatory responses to interventions is unclear. We investigated associations of certain polymorphisms with response to a lifestyle intervention. METHODS This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the fat mass and obesity-associated (FTO) T/A, peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala, and ApoA1 -75G/A polymorphisms. Changes in metabolic and inflammatory variables were analyzed according to these polymorphisms. RESULTS The intervention resulted in lower energy intake and higher physical activity. Anthropometric measurements, 2-hr plasma glucose, insulin, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB) improved significantly for the total sample, and these benefits were similar among genotypes. Only variant allele carriers of FTO T/A decreased fasting plasma glucose after intervention (99.9±1.3 to 95.6±1.4 mg/dL, P=0.021). Mean blood pressure reduced after intervention in variant allele carriers of the PPARγ Pro12Ala (109.4±2.1 to 101.3±2.1 mmHg, P<0.001). Improvement in lipid variables was not significant after adjustment for medication. Only the reference genotype of PPARγ Pro12Ala increased apolipoprotein A1 (ApoA1) after intervention (134.3±2.4 to 140.6±2.3 mg/dL, P<0.001). Only variant allele carriers of FTO reduced C-reactive protein (CRP) concentration (0.366±0.031 to 0.286±0.029 mg/dL, P=0.023). CONCLUSION In Brazilian individuals, the FTO T/A polymorphism induces a favorable impact on inflammatory status and glucose metabolism. The reference genotype of PPARγ Pro12Ala seems to favor a better lipid profile, while the variant allele decreases blood pressure. Our data did not support benefits of the variant allele of ApoA1 -75G/A polymorphism. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.
-
7.
Short-term walnut consumption increases circulating total adiponectin and apolipoprotein A concentrations, but does not affect markers of inflammation or vascular injury in obese humans with the metabolic syndrome: data from a double-blinded, randomized, placebo-controlled study.
Aronis, KN, Vamvini, MT, Chamberland, JP, Sweeney, LL, Brennan, AM, Magkos, F, Mantzoros, CS
Metabolism: clinical and experimental. 2012;(4):577-82
-
-
Free full text
-
Abstract
Long-term consumption of walnuts is associated with lower cardiovascular disease risk in epidemiological studies, possibly through improvements in lipid profile and endothelial function. It remains to be elucidated how soon after initiation of walnut consumption beneficial effects on lipid profile and biomarkers of inflammation or vascular injury can be observed. Fifteen obese subjects (9 men and 6 women; age, 58 ± 2.5 years; body mass index, 36.6 ± 1.7 kg/m(2)) with the metabolic syndrome participated as inpatients in a randomized, double-blinded, placebo-controlled crossover study involving short-term placebo or walnut-enriched diet (48 g/d for 4 days). Apolipoproteins and markers of inflammation and vascular injury were measured before and after consumption of the experimental diets. Consumption of walnuts was associated with a statistically significant increase in serum apolipoprotein A concentrations (P = .03), but did not affect circulating levels of fetuin A, resistin, C-reactive protein, serum amyloid A, soluble intercellular adhesion molecules 1 and 3, soluble vascular cell adhesion protein 1, interleukins 6 and 8, tumor necrosis factor α, E-selectin, P-selectin, and thrombomodulin. Four days of walnut consumption (48 g/d) leads to mild increases in apolipoprotein A concentrations, changes that may precede and lead to the beneficial effects of walnuts on lipid profile in obese subjects with the metabolic syndrome.
-
8.
Effect of apolipoprotein C3 and apolipoprotein A1 polymorphisms on postprandial response to a fat overload in metabolic syndrome patients.
Clemente-Postigo, M, Queipo-Ortuño, M, Valdivielso, P, Tinahones, FJ, Cardona, F
Clinical biochemistry. 2010;(16-17):1300-4
Abstract
OBJECTIVES Apolipoprotein C-III (APOC3) is a component of triglyceride rich lipoproteins, and SstI polymorphism has been associated with hypertriglyceridemia. Apolipoprotein A-I (APOA1) is the major component of HDL and MspI polymorphism has been associated with APOA1 and HDL-C levels. Thus, we study the influence of these polymorphisms in the postprandial response in metabolic syndrome (MS). DESIGN AND METHODS 73 MS patients and 21 healthy subjects underwent a fat overload, with measurements of their fasting and postprandial lipid profile. The APOC3 SstI and the APOA1MspI polymorphisms were genotyped. RESULTS No significant differences were found in the lipid profile with respect to the MspI genotype. Patients with the S2S2 APOC3 genotype had significantly higher fasting and postprandial triglyceride levels and postprandial APOC3 and chylomicron-triglyceride levels compared with the other SstI APOC3 genotypes. CONCLUSIONS Homozygosity for the minor allele of the APOC3 SstI polymorphism was associated to a worse postprandial response in MS patients.
-
9.
The paradox of high apolipoprotein A-I levels independently predicting incident type-2 diabetes among Turks.
Onat, A, Hergenç, G, Bulur, S, Uğur, M, Küçükdurmaz, Z, Can, G
International journal of cardiology. 2010;(1):72-9
Abstract
BACKGROUND Predictive value of apolipoprotein (apo) A-I for incident hypertension, metabolic syndrome (MetS), type 2 diabetes (DM) and coronary heart disease (CHD) needs further exploration. METHODS A representative sample of Turkish adults was studied with this purpose prospectively. Sex-specific apoA-I tertiles were examined regarding cardiometabolic risk. RESULTS AND CONCLUSIONS A total of 1044 men and 1067 women (aged 49+/-12 years at baseline) were followed up over 7.4 years. High serum apoA-I levels were significantly associated in multivariable analysis with female sex, aging, alcohol intake, (inversely) cigarette smoking and, in women, with systolic blood pressure. Risk of diabetes was predicted in logistic regression in both genders by top versus bottom apoA-I tertile (RR 1.98; [95%CI 1.31; 3.0]), additive to age, body mass index (BMI), C-reactive protein (CRP), HDL-cholesterol and lipid lowering drugs. By adding sex hormone-binding globulin to the model in a subset of the sample, the association between high apoA-I and incident diabetes was attenuated only in women. ApoA-I tertiles tended to be positively associated also with hypertension and CHD only in women but this did not reach significance. High compared with low serum apoA-I levels nearly double the risk for incident diabetes, additively to age, BMI, CRP, HDL-cholesterol among Turks. Systemic inflammation concomitant with prevailing MetS might turn apoA-I into proinflammatory particles.
-
10.
Apolipoprotein measurements: is more widespread use clinically indicated?
Davidson, MH
Clinical cardiology. 2009;(9):482-6
Abstract
Apolipoprotein (apo) B may be a more sensitive measure of atherogenicity than low-density lipoprotein cholesterol (LDL-C) and a better index for assessing cardiovascular risk. The refined risk assessment provided by apo B may be important in patients at high cardiometabolic risk such as those with diabetes mellitus or metabolic syndrome, as these conditions are often associated with normal LDL-C values but increased numbers of small, dense low-density lipoprotein (LDL) particles (indicating increased levels of apo B). Although apo B is not currently a treatment target in the United States cholesterol-lowering guidelines, a consensus conference endorsed by the American Diabetes Association and the American College of Cardiology recently recommended that apo B be added as a therapeutic target in patients at high cardiometabolic risk and in patients with clinical cardiovascular disease or diabetes. Suggested target goals are < 90 for high risk and < 80 mg/dL for highest risk patients. Current clinical data indicate that intensive statin therapy can lower apo B to meet this aggressive goal. While the proatherogenic/antiatherogenic ratio of apo B/apo A-I is a better risk discriminator than the single proatherogenic measurement (apo B), clinical trial data are lacking regarding the impact of increasing apo A-I and high-density lipoprotein on outcomes.