The role of serum lipid profile in the pathogenesis of arterial hypertension
Abstract
Hypertension is a key contributor to the high global burden of cardiovascular morbidity and mortality, due to its increasing prevalence worldwide. In clinical practice, dyslipidemia and hypertension often coexist, possibly because they share similar underlying causes, such as endothelial dysfunction and obesity. Consequently, this review article presents the collective findings on the role of lipid profile parameters in arterial hypertension. Individuals with hypertension often have significantly higher mean serum levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while exhibiting lower mean serum levels of high-density lipoprotein cholesterol (HDL-C) compared to those without hypertension. TC and HDL-C play an important role in the pathogenesis of arterial hypertension. However, there is a lack of studies explaining the link between TG and LDL-C and arterial hypertension. Future studies are necessary to fully elucidate the exact mechanisms by which the mentioned lipid parameters contribute to arterial hypertension.
References
Kearney PM, Reynolds K, Munter P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217-3.
Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16(4):223-237.
D’Elia L, Brajović M, Klisic A, Breda J, Jewell J, Cadjenović V, Cappuccio FP. Sodium and potassium intake, knowledge attitudes and behaviour towards salt consumption, amongst adults in Podgorica, Montenegro. Nutrients. 2019;11(1):160.
Klisic A, Kavaric N, Bjelakovic B, Soldatovic I, Martinovic M, Kotur-Stevuljevic J. The association between retinol-binding protein 4 and cardiovascular risk score is mediated by waist circumference in overweight/obese adolescent girls. Acta Clin Croat. 2017;56:92-98.
Klisic A, Kavaric N, Ninic A. Are liver function biomarkers independently associated with Framingham risk score in female population? Srpski arhiv za celokupno lekarstvo. 2020. doi: 10.2298/SARH181120006K.
Klisić A, Kavarić N, Bjelaković B, Jovanović M, Zvrko E, Škerović V, et al. Cardiovascular risk assessed by Reynolds risk score in relation to waist circumference in apparently healthy middle-aged population in Montenegro. Acta Clin Croat. 2018;57:22-30.
Klisic A, Kavaric N, Vujcic S, Spasojevic-Kalimanovska V, Ninic A, Kotur-Stevuljevic J. Endocan and advanced oxidation protein products in adult population with hypertension. Eur Rev Med Pharmacol Sci. 2020;24(12):7131-7137.
Klisic A, Kavaric N, Vujcic S, Spasojevic-Kalimanovska V, Kotur-Stevuljevic J, Ninic A. Total oxidant status and oxidative stress index as indicators of increased Reynolds Risk Score in postmenopausal women. Eur Rev Med Pharmacol Sci. 2020;24(19):10126-10133.
Klisic A, Kotur-Stevuljevic J, Kavaric N, Martinovic M, Matic M. The association between follicle stimulating hormone and glutathione peroxidase activity is dependent on abdominal obesity in postmenopausal women. Eat Weight Disord. 2018;23:133-141.
Klisic A, Kocic G, Kavaric N, Jovanovic M, Stanisic V, Ninic A. Body mass index is independently associated with xanthine oxidase activity in overweight/obese population. Eat Weight Disord. 2020;25:9-15.
Klisic A, Kavaric N, Ninic A, Kotur-Stevuljevic J. Oxidative stress and cardiometabolic biomarkers in patients with non-alcoholic fatty liver disease. Sci Rep. 2021;11:18455.
Nigam PK. Serum lipid profile: fasting or non-fasting? Indian J Clin Biochem. 2011;26:96-7.
Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: a pathophysiologic approach. Connecticut: Appleton and Lange; 2014.
Ke C, Zhu X, Zhang Y, Shen Y. Metabolomic characterization of hypertension and dyslipidemia. Metabolomics. 2018;14:1-1.
Dąbrowska E, Narkiewicz K. Hypertension and Dyslipidemia: the Two Partners in Endothelium-Related Crime. Curr Atheroscler Rep. 2023;25(9):605-612.
Selwyn AP, Kinlay S, Libby P, Ganz P. Atherogenic lipids, vascular dysfunction, and clinical signs of ischemic heart disease. Circulation. 1997;95(1):5-7.
McGill JB, Haffner S, Rees TJ, Sowers JR, Tershakovec AM, Weber M. Progress and controversies: treating obesity and insulin resistance in the context of hypertension. J Clin Hypertens (Greenwich). 2009;11(1):36-41.
Osuji CU, Omejua EG, Onwubuya EI, Ahaneku GI. Serum lipid profile of newly diagnosed hypertensive patients in nnewi, South-East Nigeria. Int J Hypertens. 2012;2012:710486.
Liu D, Guan L, Zhao Y, Liu Y, Sun X, Li H, et al. Association of triglycerides to high-density lipoprotein-cholesterol ratio with risk of incident hypertension. Hypertens Res. 2020;43:948-955.
Prasad M, Sara J, Widmer RJ, Lennon R, Lerman LO, Lerman A. Triglyceride and triglyceride/HDL (High Density Lipoprotein) ratio predict major adverse cardiovascular outcomes in women with non-obstructive coronary artery disease. J Am Heart Assoc. 2019;8:e009442.
Klisic A, Kavaric N, Soldatovic I, Bjelakovic B, Kotur-Stevuljevic J. Relationship between cardiovascular risk score and traditional and nontraditional cardiometabolic parameters in obese adolescent girls. J Med Biochem. 2016;35:282-292.
Kurtkulagi O, Aktas G, Taslamacioglu Duman T, Bilgin S, Atak Tel BM, Kahveci G. Correlation between serum triglyceride to HDL cholesterol ratio and blood pressure in patients with primary hypertension. Precision Medical Sciences. 2022;11(3):100-5.
Hong M, Ling Y, Lu Z, Liu Y, Gu P, Shao J, et al. Contribution and interaction of the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and triglyceride to diabetes in hypertensive patients: A cross-sectional study. J Diabetes Investig. 2019;10(1):131-138.
Wu H, Yu Z, Huang Q. Characteristics of serum lipid levels in patients with hypertension: a hospital-based retrospective descriptive study. BMJ Open. 2022;12(6):e054682.
Choudhury KN, Mainuddin AK, Wahiduzzaman M, Islam SM. Serum lipid profile and its association with hypertension in Bangladesh. Vasc Health Risk Manag. 2014;10:327-32.
Anika UL, Pintaningrum Y, Syamsun A. Correlation between serum lipid profile and blood pressure in NTB general hospital. J Hypertens. 2015;33:e32.
Harvey JM, Beevers DG. Biochemical investigation of hypertension. Ann Clin Biochem. 1990;27(4):287-96.
Klisic A, Kavaric N, Vujcic S, Spasojevic-Kalimanovska V, Ninic A, Kotur-Stevuljevic J. Endocan and advanced oxidation protein products in adult population with hypertension. Eur Rev Med Pharmacol Sci. 2020;24(12):7131-7137.
Poznyak AV, Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova EV, Orekhov AN. Overview of OxLDL and Its Impact on Cardiovascular Health: Focus on Atherosclerosis. Front Pharmacol. 2021;11:613780.
Borghi C. Interactions between hypercholesterolemia and hypertension: implications for therapy. Curr Opin Nephrol Hypertens. 2002;11(5):489-96.
Borghi C, Rodriguez-Artalejo F, De Backer G, Dallongeville J, Medina J, Guallar E, et al. The association between blood pressure and lipid levels in Europe: European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice. J Hypertens. 2016;34(11):2155-63.
Pereira AC, Sposito AC, Mota GF, Cunha RS, Herkenhoff FL, Mill JG, Krieger JE. Endothelial nitric oxide synthase gene variant modulates the relationship between serum cholesterol levels and blood pressure in the general population: new evidence for a direct effect of lipids in arterial blood pressure. Atherosclerosis. 2006;184(1):193-200.
Deming QB, Mosbach EH, Bevans M, Daly MM, Abell LL, Martin E, et al. Blood pressure, cholesterol content of serum and tissues and atherogenesis in the rat. J Exp Med. 1958;107(4):581-98.
Borghi C, Veronesi M, Cosentino E, Cicero AF, Kuria F, Dormi A, Ambrosioni E. Interaction between serum cholesterol levels and the renin-angiotensin system on the new onset of arterial hypertension in subjects with high-normal blood pressure. J Hypertens. 2007;25(10):2051-7.
Strehlow K, Wassmann S, Böhm M, Nickenig G. Angiotensin AT1 receptor over-expression in hypercholesterolaemia. Ann Med. 2000;32(6):386-9.
Satoh M, Ohkubo T, Asayama K, Murakami Y, Sakurai M, Nakagawa H, et al. Combined effect of blood pressure and total cholesterol levels on long-term risks of subtypes of cardiovascular death: evidence for cardiovascular prevention from observational cohorts in Japan. Hypertension. 2015;65(3):517-24.
Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12:204-12.
Businaro R, Tagliani A, Buttari B, Profumo E, Ippoliti F, Di Cristofano C, et al. Cellular and molecular players in the atherosclerotic plaque progression. Ann N Y Acad Sci. 2012;1262:134-41.
Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol. 2010;10(1):36-46.
Kubozono T, Miyata M, Kawasoe S, Ojima S, Yoshifuku S, Miyahara H, et al. High Pulse Wave Velocity Has a Strong Impact on Early Carotid Atherosclerosis in a Japanese General Male Population. Circ J. 2017;81(3):310-315.
Humphrey JD, Harrison DG, Figueroa CA, Lacolley P, Laurent S. Central Artery Stiffness in Hypertension and Aging: A Problem With Cause and Consequence. Circ Res. 2016;118(3):379-81.
Chen H, Chen Y, Wu W, Cai Z, Chen Z, Yan X, Wu S. Total cholesterol, arterial stiffness, and systolic blood pressure: a mediation analysis. Sci Rep. 2021;11(1):1-7.
Bjelakovic B, Stefanutti C, Vukovic V, Kavaric N, Saranac L, Klisic A, et al. Lipid profile and left ventricular geometry pattern in obese children. Lipids Health Dis. 2020;19(1):109.
Tomita Y, Sakata S, Arima H, Yamato I, Ibaraki A, Ohtsubo T, et al. Relationship between casual serum triglyceride levels and the development of hypertension in Japanese. J Hypertens. 2021;39(4):677-682.
Raposeiras-Roubin S, Rosselló X, Oliva B, Fernández-Friera L, Mendiguren JM, Andrés V, et al. Triglycerides and Residual Atherosclerotic Risk. J Am Coll Cardiol. 2021;77(24):3031-3041.
Kawamoto R, Tabara Y, Kohara K, Kusunoki T, Abe M, Miki T. Interaction between serum uric acid and triglycerides in relation to prehypertension in community-dwelling Japanese adults. Clin Exp Hypertens. 2014;36(1):64-9.
Bogavac-Stanojević N, Jelić-Ivanović Z, Memon L, Zeljković A, Vekić J, Kotur-Stevuljević J, Spasojević-Kalimanovska V. Biomarkeri prehipertenzije. Arch Pharm. 2013;63:307-318.
Fletcher AE, Bulpitt CJ. How far should blood pressure be lowered? N Engl J Med. 1992;326(4):251-4.
Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. High triglycerides and low HDL cholesterol and blood pressure and risk of ischemic heart disease. Hypertension. 2000;36(2):226-32.
Deng S, Xu Y, Zheng L. HDL Structure. In: Zheng L, editor. HDL Metabolism and Diseases. Singapore: Springer Nature Singapore; 2022; pp. 1-11.
Trimarco V, Izzo R, Morisco C, Mone P, Virginia Manzi M, Falco A, et al. High HDL (high-density lipoprotein) cholesterol increases cardiovascular risk in hypertensive patients. Hypertension. 2022;79(10):2355-63.
Chruściel P, Stemplewska P, Stemplewski A, Wattad M, Bielecka-Dąbrowa A, Maciejewski M, et al. Associations between the lipid profile and the development of hypertension in young individuals–the preliminary study. Arch Med Sci. 2022;18(1):25-35.
Ivanišević J, Ardalić D, Banjac G, Janać J, Cabunac P, Vekić J, et al. Antioxidant status in hypertensive disorders of pregnancy. Hypertens Pregnancy. 2022;41(1):31-38.
Pavithran P, Nandeesha H, Madanmohan, Bobby Z, Sathiyapriya V, Shenoy P, et al. Dyslipidemia antedates occurrence of clinical hypertension in non-diabetic, non-obese male subjetcs. Indian J Physiol Pharmacol. 2007;51(1):96-8.
Klisic A, Kavaric N, Vujcic S, Mihajlovic M, Zeljkovic A, Ivanisevic J, et al. Inverse association between serum endocan levels and small LDL and HDL particles in patients with type 2 diabetes mellitus. Eur Rev Med Pharmacol Sci. 2020;24(15):8127-8135.
Klisic A, Kavaric N, Ninic A. Serum Cystatin C levels are associated with Triglycerides/High-density lipoprotein cholesterol ratio in adolescent girls ages between 16-19 years old. Eur Rev Med Pharmacol Sci. 2020;24(20):10680-10686.
Chen S, Cheng W. Relationship Between Lipid Profiles and Hypertension: A Cross-Sectional Study of 62,957 Chinese Adult Males. Front Public Health. 2022;10:895499.
Al-Jarallah A, Babiker F. High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner. Front Cardiovasc Med. 2022;9:825310.
Whayne TF. Low-Density Lipoprotein Cholesterol (LDL-C): How Low? Curr Vasc Pharmacol. 2017;15(4):374-379.
Tsukinoki R, Okamura T, Watanabe M, Kokubo Y, Higashiyama A, Nishimura K, et al. Blood pressure, low-density lipoprotein cholesterol, and incidences of coronary artery disease and ischemic stroke in Japanese: the Suita study. Am J Hypertens. 2014;27(11):1362-9.
Yan X, Li Y, Dong Y, Wu Y, Li J, Bian R, Hu D. Blood pressure and low-density lipoprotein cholesterol control status in Chinese hypertensive dyslipidemia patients during lipid-lowering therapy. Lipids Health Dis. 2019;18(1):32.
Milošević M, Otašević P. Treatment-resistant hypertension. Arch Pharm. 2022;72:1-19.
Bekhet OH, Zeljkovic A, Vekic J, Paripovic D, Janac J, Joksic J, et al. Hypertension, lipoprotein subclasses and lipid transfer proteins in obese children and adolescents. Scand J Clin Lab Invest. 2016;76(6):472-8.
Rached F, Santos RD. The Role of Statins in Current Guidelines. Curr Atheroscler Rep. 2020;22(9):50.
Spannella F, Filipponi A, Giulietti F, Di Pentima C, Bordoni V, Sarzani R. Statin therapy is associated with better ambulatory blood pressure control: a propensity score analysis. J Hypertens. 2020;38(3):546-552.
Nurmohamed NS, Ditmarsch M, Kastelein JJP. Cholesteryl ester transfer protein inhibitors: from high-density lipoprotein cholesterol to low-density lipoprotein cholesterol lowering agents? Cardiovasc Res. 2022;118(14):2919-2931.
Taheri H, Filion KB, Windle SB, Reynier P, Eisenberg MJ. Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cardiology. 2020;145(4):236-250.
Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, Collins R, et al.; HPS3/ TIMI55–REVEAL Collaborative Group. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. N Engl J Med. 2017;377(13):1217–27.
Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. dal-OUTCOMES Investigators. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367(22): 2089–99.
Suico JG, Wang MD, Friedrich S, Cannady EA, Konkoy CS, Ruotolo G, et al. Effects of the cholesteryl ester transfer protein inhibitor evacetrapib on lipoproteins, apolipoproteins and 24-h ambulatory blood pressure in healthy adults. J Pharm Pharmacol. 2014;66(11):1576–85.