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Kazibwe R, Jehopio J, Schaich CL, Rikhi R, Mirzai S, Chevli PA, Namutebi JH, Chebrolu S, O'Connor S, Yeboah J, Shapiro MD. Atherogenic dyslipidemia and incident cardiovascular events in high-risk hypertension. Prog Cardiovasc Dis 2025:S0033-0620(25)00069-6. [PMID: 40393568 DOI: 10.1016/j.pcad.2025.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2025] [Revised: 04/25/2025] [Accepted: 05/12/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Atherogenic dyslipidemia (AD), characterized by low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides (TG), is associated with increased cardiovascular disease (CVD) risk. This study evaluates the association between AD and CVD in hypertension treated to systolic blood pressure (SBP) targets of <120 mmHg (intensive) or < 140 mmHg (standard). METHODS We included 9361 participants from the Systolic Blood Pressure Intervention Trial (SPRINT). Based on baseline lipid profiles, low HDL-C was defined as <40 mg/dL in men or < 50 mg/dL in women, and high TG as ≥150 mg/dL. Participants were classified into four lipid categories according to these cutoffs. AD was defined as the combination of low HDL-C and high TG. We used multivariable Cox regression to evaluate the association between lipid categories and the primary SPRINT outcome, a composite of major CVD events. RESULTS Over a median 3.8-year follow-up, 726 primary outcome events occurred. The incidence of the primary outcome was 9.5% (n = 104) in those with AD and 7.4% (n = 434) with normal HDL-C and TG. Compared to the reference group (normal HDL-C with normal TG), the hazard ratios (HRs) for primary outcome were 1.07 (95 % CI: 0.85-1.35) for high TG alone, 1.20 (95 % CI: 0.95-1.52) for low HDL-C alone, and 1.41 (95 % CI: 1.12-1.77) for AD. Similarly, HRs for the primary outcome associated with AD were 1.38 (95 % CI: 1.02-1.87) and 1.44 (95 % CI: 1.01-2.05) in the standard and intensive SBP-lowering arms, respectively. CONCLUSION Among SPRINT participants, AD was associated with a higher CVD risk. Early detection of AD in hypertensive patients, even without diabetes, may prompt greater therapeutic effort to reduce long-term CVD risk.
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Affiliation(s)
- Richard Kazibwe
- Department of Internal Medicine, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Jeshuah Jehopio
- Uganda Christian University, School of Medicine, P.O. Box 4, Mukono, Uganda.
| | - Christopher L Schaich
- Hypertension and Vascular Research Center, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Rishi Rikhi
- Division of Cardiology, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Saeid Mirzai
- Division of Cardiology, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Parag A Chevli
- Division of Cardiology, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Juliana H Namutebi
- Wake Forest University, School of Biomedical Graduate Studies, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Sneha Chebrolu
- Department of Internal Medicine, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Shannon O'Connor
- Department of Internal Medicine, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Joseph Yeboah
- Division of Cardiology, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Michael D Shapiro
- Center for the Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
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Prognostic significance of multiple triglycerides-derived metabolic indices in patients with acute coronary syndrome. J Geriatr Cardiol 2022; 19:456-468. [PMID: 35845160 PMCID: PMC9248272 DOI: 10.11909/j.issn.1671-5411.2022.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Triglyceride (TG) and its related metabolic indices, all recognized as surrogates of insulin resistance, have been demonstrated to be relevant to clinical prognosis. However, the relative value of these TG-related indices for predicting cardiovascular events among patients with acute coronary syndrome (ACS) has not been examined. METHODS The TG, the triglyceride-glucose (TyG) index, the atherogenic index of plasma, TG to high-density lipoprotein cholesterol ratio, and the lipoprotein combine index were assessed in 1694 ACS patients undergoing percutaneous coronary intervention. The primary endpoint was major adverse cardiovascular event (MACE), which was the composite of all-cause mortality, stroke, myocardial infarction, or unplanned repeat revascularization. RESULTS During a median follow-up of 31 months, 345 patients (20.4%) had MACE. The risk of the MACE was increased with higher TG and the four TG-derived metabolic indices [TG-adjusted hazard ratio (HR) = 1.002, 95% CI: 1.001-1.003; TyG index-adjusted HR = 1.736, 95% CI: 1.398-2.156; atherogenic index of plasma-adjusted HR = 2.513, 95% CI: 1.562-4.043; TG to high-density lipoprotein cholesterol ratio-adjusted HR = 1.148, 95% CI: 1.048-1.258; and lipoprotein combine index-adjusted HR = 1.009, 95% CI: 1.004-1.014; P < 0.001 for all indices]. TG and all the four indices significantly improved the predictive ability for MACE in addition to the baseline model. Among them, TyG index showed the best ability for predicting MACE compared with the other three indices from all the three measurements ( P < 0.05 for all comparison). CONCLUSIONS TG and TG-derived metabolic indices were all strongly associated with MACE among ACS patients undergoing percutaneous coronary intervention. Among all the indices, TyG index showed the best ability to predict the risk of MACE.
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Sultani R, Tong DC, Peverelle M, Lee YS, Baradi A, Wilson AM. Elevated Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio Predicts Long-Term Mortality in High-Risk Patients. Heart Lung Circ 2019; 29:414-421. [PMID: 31014557 DOI: 10.1016/j.hlc.2019.03.019] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 03/25/2019] [Accepted: 03/31/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND Elevated triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been utilised as a predictor of outcomes in patients with adverse cardiometabolic risk profiles. In this study, we examined the prognostic value of elevated TG/HDL-C level in an Australian population of patients with high clinical suspicion of coronary artery disease (CAD) presenting for coronary angiography. METHODS Follow-up data was collected for 482 patients who underwent coronary angiography in a prospective cohort study. The primary endpoint was all-cause mortality and the secondary endpoint was a major adverse cardiac event (MACE). Patients were stratified into two groups according to their baseline TG/HDL-C ratio, using a TG/HDL-C ratio cut point of 2.5. RESULTS The mean follow-up period was 5.1 ± 1.2 years, with 49 all-cause deaths. Coronary artery disease on coronary angiography was more prevalent in patients with TG/HDL-C ratio ≥2.5 (83.6% vs. 69.4%, p = 0.03). On the Kaplan-Meier analysis, patients with TG/HDL-C ratio ≥2.5 had worse long-term prognosis (p = 0.04). On multivariate Cox regression adjusting for established cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was an independent predictor of long-term all-cause mortality (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.04-4.20, p = 0.04). On multivariate logistic regression adjusting for known cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was strongly associated with an increased risk of long-term MACE (odds ratio [OR] 2.72, 95% CI 1.42-5.20, p = 0.002). CONCLUSIONS Elevated TG/HDL-C ratio is an independent predictor of long-term all-cause mortality and is strongly associated with an increased risk of MACE.
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Affiliation(s)
- Rohullah Sultani
- Department of Cardiology, St. Vincent's Hospital, Melbourne, Vic, Australia; University of Melbourne, Department of Medicine, St. Vincent's Hospital, Melbourne, Vic, Australia.
| | - David C Tong
- Department of Cardiology, St. Vincent's Hospital, Melbourne, Vic, Australia; Department of Cardiology, Peninsula Health, Melbourne, Vic, Australia
| | - Matthew Peverelle
- Department of Cardiology, St. Vincent's Hospital, Melbourne, Vic, Australia; University of Melbourne, Department of Medicine, St. Vincent's Hospital, Melbourne, Vic, Australia
| | - Yun Suk Lee
- Department of Cardiology, St. Vincent's Hospital, Melbourne, Vic, Australia; University of Melbourne, Department of Medicine, St. Vincent's Hospital, Melbourne, Vic, Australia
| | - Arul Baradi
- Department of Cardiology, Werribee Mercy Hospital, Melbourne, Vic, Australia; Department of Cardiology, St. Vincent's Private Hospital, Melbourne, Vic, Australia
| | - Andrew M Wilson
- Department of Cardiology, St. Vincent's Hospital, Melbourne, Vic, Australia; Department of Cardiology, St. Vincent's Private Hospital, Melbourne, Vic, Australia
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Sponder M, Fritzer-Szekeres M, Marculescu R, Litschauer B, Strametz-Juranek J. A new coronary artery disease grading system correlates with numerous routine parameters that were associated with atherosclerosis: a grading system for coronary artery disease severity. Vasc Health Risk Manag 2014; 10:641-7. [PMID: 25404859 PMCID: PMC4230172 DOI: 10.2147/vhrm.s68919] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background Several scoring systems have tried to determine the severity of coronary artery disease (CAD) to investigate the connection between CAD severity and laboratory parameters. Methods In total, 189 male (mean age: 61.86±10.77 years) and 75 female CAD patients (mean age: 67.84±7.70 years) were recruited and underwent angiography, which determined stenosis grade, of 17 coronary segments: no points for each nonstenosed segment or only calcified segments, one point for each stenosis from <30% to <50%, two points for each stenosis from 50% to <70%, and three points for each stenosis >70%. The points were added and should represent the severity of patients’ CAD. Results The coronary score correlated positively with systolic blood pressure, creatinine, blood urea nitrogen, lipase, glucose, glycated hemoglobin, triglycerides, C-reactive protein, fibrinogen Clauss, and leukocytes, and correlated negatively with Cl−, iron, and high-density lipoprotein cholesterol. Stepwise multiple regression analysis with backward elimination revealed diabetes status, sex, and fibrinogen Clauss as significant predictors of coronary score. Conclusion The coronary score delivers a quite simple but very precise tool for the quantification of CAD severity. These results show plainly the connection between CAD severity and the lipid, glucose, coagulation, and immunologic status of CAD patients, and substantiate the importance of sufficient treatment in this group of patients – in particular, CAD patients suffering from type 2 diabetes mellitus. The coronary score would offer a suitable tool for the investigation of the connection between CAD and new biomarkers. Further studies are needed to investigate the correlation of the coronary score with outcome parameters (eg, death).
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Affiliation(s)
- Michael Sponder
- Department of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Monika Fritzer-Szekeres
- Department of Medical-Chemical Laboratory Analysis, Medical University of Vienna, Vienna, Austria
| | - Rodrig Marculescu
- Department of Medical-Chemical Laboratory Analysis, Medical University of Vienna, Vienna, Austria
| | - Brigitte Litschauer
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
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Sobenin IA, Chistiakov DA, Sazonova MA, Ivanova MM, Bobryshev YV, Orekhov AN, Postnov AY. Association of the level of heteroplasmy of the 15059G>A mutation in the MT-CYB mitochondrial gene with essential hypertension. World J Cardiol 2013; 5:132-40. [PMID: 23710300 PMCID: PMC3663127 DOI: 10.4330/wjc.v5.i5.132] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2012] [Revised: 03/14/2013] [Accepted: 03/28/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To examine whether the heteroplasmy level for 15059G>A mutation in the mitochondrial genome might be associated with essential hypertension. METHODS This cross-sectional study involved 196 unrelated participants randomly selected from general population (90 males and 106 females) who underwent a regular medical check-up at the Institute for Atherosclerosis Research (Moscow, Russia). One hundred and twenty of them (61%) had essential hypertension, and 76 (39%) were apparently healthy normotensive persons. The level of heteroplasmy for 15059G>A mutation occurring in the coding region of cytochrome b gene (MT-CYB) of mtDNA isolated from the blood leukocytes, was quantified using DNA pyrosequencing method. RESULTS The 15059G>A heteroplasmy level ranged between 4% and 83%, with a median level of 31%. Between the upper and lower quartiles of 15059G>A heteroplasmy distribution, significant differences were observed for patients' age, systolic blood pressure, and triglyceride levels. 15059G>A heteroplasmy correlated both with age (r = 0.331, P < 0.001) and the presence of hypertension (r = 0.228, P = 0.002). Regression analysis revealed that the age explains 12% variability of 15059G>A heteroplasmy, and hypertension independently explains more 5% variability. The 15059G>A heteroplasmy exceeding 31% was found to be significantly associated with a higher risk of essential hypertension (odds ratio 2.76; P (Fisher) 0.019]. The study participants with high 15059G>A heteroplasmy level were found to have significantly higher age (P < 0.001) and the prevalence of essential hypertension (P = 0.033), as compared to those with low 15059G>A heteroplasmy level. These observations suggested a positive correlation between the level of 15059G>A heteroplasmy and essential hypertension. CONCLUSION This study provides the evidence of association of mtDNA 15059G>A mutation heteroplasmy with essential hypertension.
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Affiliation(s)
- Igor A Sobenin
- Igor A Sobenin, Margarita A Sazonova, Anton Y Postnov, Russian Cardiology Research and Production Complex, 121552 Moscow, Russia
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Nikitin AG, Lavrikova EY, Chistiakov DA. The heteroplasmic 15059G>A mutation in the mitochondrial cytochrome b gene and essential hypertension in type 2 diabetes. Diabetes Metab Syndr 2012; 6:150-156. [PMID: 23158979 DOI: 10.1016/j.dsx.2012.09.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
AIM The long-term stress of high blood pressure levels increases the risk of a variety of macro- and microvascular complications of type 2 diabetes (T2D). The etiology of essential hypertension (EH) has been explored in depth, but the pathophysiology is multifactorial, complex, and poorly understood. Recent findings showed a role of inherited mutations in mitochondrial DNA (mtDNA) in maternally inherited forms of hypertension. However, an impact of somatic mtDNA mutations in the development of EH is significantly less investigated. In this study, we examined whether the level of heteroplasmy for the 15059G>A mutation in the mitochondrial cytochrome b gene is associated with EH in T2D. PATIENTS AND METHODS The heteroplasmy level in mtDNA isolated from blood of 189 diabetic participants randomly selected from general population (124 of whom had EH) was quantified using a real-time PCR. RESULTS The 15059G>A heteroplasmy exceeding 39% was found to be significantly associated with a higher risk of EH (odds ratio 1.96; P (Fisher) 0.032). CONCLUSION There is the first evidence reporting association between the mtDNA 15059G>A mutation heteroplasmy and EH in T2D.
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Affiliation(s)
- Alexey G Nikitin
- Department of Molecular Diagnostics, National Research Center GosNIIgenetika, 117545 Moscow, Russia
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Chen Z, Yin Q, Ma G, Qian Q. KCNQ1 gene polymorphisms are associated with lipid parameters in a Chinese Han population. Cardiovasc Diabetol 2010; 9:35. [PMID: 20701788 PMCID: PMC2925337 DOI: 10.1186/1475-2840-9-35] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2010] [Accepted: 08/11/2010] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Four single nucleotide polymorphisms (SNPs) (rs2237892, rs2237895, rs2237897, and rs2283228) in KCNQ1 are reported to be associated with type 2 diabetes mellitus (T2DM), possibly caused by a reduction in insulin secretion and higher fasting glucose, but the results are inconsistent. We investigated whether these 4 genetic markers are associated with serum lipid metabolism in a middle-aged Chinese Han population. METHODS We enrolled 398 consecutive patients, including 180 with premature coronary artery disease (CAD) (male < 55 years, female < 65 years) and 218 controls without documented CAD. All subjects were genotyped for 4 SNPs by using the ligase detection reaction method. Fasting blood sugar (FBS) and plasma concentrations of total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1(apo A1), and apolipoprotein B (apo B) were determined by standard biochemical methods. Main anthropometric and metabolic characteristics are analyzed among 3 genotypes at rs2283228, rs2237895, rs2237897, or rs2237892 in KCNQ1. RESULTS The 3 genotypes AA, AC, and CC were present in rs2283228 and rs2237895, and the 3 genotypes CC, CT, and TT were present in rs2237897 and rs2237892. The minor genotypes CC at rs2283228 and TT at rs2237892 were associated with higher levels of TG (P = 0.007 and 0.026, respectively). Furthermore, subjects with the CC genotype at rs2283228 had lower levels of HDL-C and apo A1 than in the other 2 genotype groups (P = 0.052 and 0.055, respectively). No other associations were detected between these 4 SNPs and FBS or other lipid parameters. CONCLUSIONS Our data suggest that rs2283228 and rs2237892 in KCNQ1 are associated with lipid metabolism in a middle-aged Chinese Han population.
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Affiliation(s)
- Zhong Chen
- Department of Cardiology, the Affiliated ZhongDa Hospital and Institute of Cardiovascular Disease of Southeast University, Nanjing 210009, PR China.
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