e components of metabolic syndrome lead to generalized atherosclerotic changes
and micro- and macrovascular complications with damage to systems and organs. Consequently,
patients’ treatment with the resulting changes in the target organs is costly, complicated, and unpredictable.
We present a 65-year-old patient with diabetes diagnosed with hyperlipidemia, unregulated
arterial hypertension in the presence of other metabolic syndrome components and who consequently
developed complications of generalized atherosclerosis. Despite detailed, individually tailored therapy,
in line with current recommendations, we suggest that treatment success is very closely related
and dependent on dietary measures, healthy living habits, and patient cooperation.Komponente metaboličkog sindroma dovode do generaliziranih aterosklerotskih promjena te mikro i makrovaskularnih
komplikacija s oštećenjem sustava i organa. Slijedom toga, liječenje bolesnika s posljedicama promjena na ciljnim organima
vrlo je skupo, složeno i nepredvidljivo. Predstavljamo 65-godišnjeg pacijenta, dijabetičara, kojem je dijagnosticirana hiperlipidemija,
neregulirana arterijska hipertenzija u prisutnosti drugih komponenata metaboličkog sindroma i posljedično razvijene
komplikacije generalizirane ateroskleroze. Unatoč detaljnoj, individualno prilagođenoj terapiji, u skladu s trenutnim
preporukama, smatramo da je uspjeh liječenja vrlo usko povezan i ovisi o prehrambenim mjerama, zdravim životnim navikama
i suradnji pacijenta

Dragan Klarić

Marta Klarić

Petra Grbić Pavlović

English

Hrčak - Portal of scientific journals of Croatia

Acta Clin Croat (Suppl. 1) 2021; 60:9-12 Case Reportdoi: 10.20471/acc.2021.60.s1.01Acta Clin Croat, Vol. 60, (Suppl. 1) 2021  9GENERALIZED ATHEROSCLEROSIS,  METABOLIC SYNDROME, AND RESISTANT HYPERTENSION - CAUSE AND CONSEQUENCESDragan Klarić¹, Petra Grbić Pavlović¹ and Marta Klarić²1Department of Nephrology and Dialysis Center, Department of Internal Medicine,  Zadar General Hospital;  2Faculty of Medicine, University of RijekaSUMMARY – The components of metabolic syndrome lead to generalized atherosclerotic chang-es and micro- and macrovascular complications with damage to systems and organs. Consequently, patients’ treatment with the resulting changes in the target organs is costly, complicated, and unpre-dictable. We present a 65-year-old patient with diabetes diagnosed with hyperlipidemia, unregulated arterial hypertension in the presence of other metabolic syndrome components and who consequent-ly developed complications of generalized atherosclerosis. Despite detailed, individually tailored ther-apy, in line with current recommendations, we suggest that treatment success is very closely related and dependent on dietary measures, healthy living habits, and patient cooperation.Key words: atherosclerosis; metabolic syndrome; renal failureCorrespondence to: Prim. Dragan Klarić, MD, Internal Medicine department, Bože Peričića 5, 23000 Zadar, CroatiaE-mail: dragan.klaric@zd.t-com.hrstudy showed a significant effect of a 1 mmHg increase in blood pressure as a 26% increase in CVR. Resistant hypertension, which we define when blood pressure is not controlled despite optimum doses of 3 first-line classes of antihypertensive drugs, including thiazide diuretic, isolated, represents a significant factor of CVR4. Elevated uric acid levels are an independent risk factor for hypertension.5The renin-angiotensin-aldosterone system (RAAS) is one of the key pathophysiological determinant of hypertension6,7,8. Its contribution is particularly im-portant in conditions of reduced glomerular filtration rate (GFR) when, in addition to increased activity of angiotensin II levels, there is also directly stimulated basally increased sympathetic tone with no decrease during the night (non-dipping). Present diabetes, as well as uncontrolled proteinuria, contribute to the fur-ther progression of kidney disease. We presented a pa-tient with long-term unregulated arterial hypertension with other components of the metabolic syndrome and the consequent development of generalized ath-erosclerosis complications.IntroductionMetabolic syndrome (MS) is a significant and growing cause of mortality and morbidity in most countries’ general population, which is why cardiovas-cular risk assessment (CVR) models1,2,3 have been de-veloped. Metabolic syndrome is the medical term for a combination of diabetes, high blood pressure (hyper-tension), and obesity (add ref.-www.nhs.uk). Hyper-tension alone, and especially within MS, is one of the main risk factors for developing atherosclerosis. The goal of treatment is to achieve the maximum reduction in overall cardiovascular risk and mortality. In addition to all preventive and non-pharmacological measures that can be implemented and adequate treatment of diabetes and dyslipidemia, pharmacological blockade of the sympathetic nervous system with indirect re-duction of catecholamine levels and modification of baroreceptor sensitivity is desirable. The ASCOT D. Klarić et al. Generalized atherosclerosis, metabolic syndrome, and resistant hypertension10 Acta Clin Croat, Vol. 60, (Suppl. 1) 2021Case ReportA 65-year-old patient, long-standing nicotinism, obese, diabetic for over 15 years without signs of dia-betic retinopathy, suffers from hyperlipidemia, unregu-lated arterial hypertension (for over 10 years), and gen-eralized atherosclerosis. He was hospitalized for a planned kidney biopsy based on nephrotic proteinuria and azotemia. In physical examination: obesity (BMI 33.4 kg/m²), pasty peripheral edema, thinned, pale skin of the lower extremities with hair loss, toenails on the remaining toes deformed. There was a significant difference in arterial pressure between the right (220/120 mmHg) and left arm (130/80 mmHg) with weakened distal arterial pulsations on lower extremi-ties. He had an amputated toe on his left foot and the first three toes on his right foot. Subjectively, he com-plained of pain in his legs with a significant reduction in the walking distance of 100-200 meters and erectile dysfunction. Laboratory findings: glucose 16.6 mmol/L HbA1C 8.7% urea 19.9 mmol/L, creatinine 172 µmol/L, creatinine clearance 37.1 ml/min, 24-hour proteinuria 2.99 - 4.37 g/dU. Urine: proteins ++/+++, cholesterol 6.0 mmol/L, HDL-K 1.39 mmol/L, LDL - K 3.37 mmol/L, triglycerides 2.61 mmol/L, urate 504 µmol/L. Ambulatory blood pres-sure monitoring (ABPM) confirmed the absence of nocturnal drop (non-dipper). Before the hospitaliza-tion, he was taking ACE inhibitor in low dose, thia-zide diuretic, CCB low dose, BB, and short-acting in-sulin 3 times a day. Aortic angiography describes se-vere atheromatosis of the abdominal aorta, significant stenosis of the superior mesenteric artery, atheroscle-rotic altered major branches of the renal arteries (no significant stenoses) with significantly stenosed acces-sory renal arteries for the lower pole of both sides. From the L3 level, the infrarenal abdominal aorta was occluded, as was the iliac artery (AIC) bilaterally. Pres-ent occlusion of the left subclavian artery and vertebral artery (VA) in a section 2 cm long and significant ste-nosis of the ostium of the left vertebral artery. He had ischemic heart disease with a percutaneous coronary intervention (PCI) where coronary angiography re-vealed significantly stenosed and calcified left anterior descending (LAD) coronary artery, which is resolved in two acts (due to hemodynamic instability of the pa-tient) by implantation of a 2 stents-DES (“drug-elut-ing stent”). According to cardiac ultrasound, he had mild concentric hypertrophy of the left ventricular wall, normal systolic function (EF about 60%) without clear regional outbursts of contractility. The left atrium was enlarged. The right ventricle was normal size, mild aortic valve atheromatosis with normal function. Col-or Doppler indicates mitral regurgitation (MI) of the first degree and tricuspid insufficiency (TI) of the first degree without indirect indicators of pulmonary hy-pertension. A kidney biopsy was performed. At the level of light and immunofluorescence microscopy in-dicate diabetic nephropathy class III with advanced nephroangiosclerosis and perihilar sclerosis that prob-ably refers to a secondary form of focal segmental glo-merulosclerosis. The X-ray of the right foot showed osteolysis of the distal part of the distal phalanx of the third toe. Ekg showed sinus rhythm, frequency 70/min, biphasic T wave in leads D1, aVL, and V5-V6. Figure 1. Severe abdominal aortic atheromatosis. T he main branches of the renal arteries are atherosclerotic changed, distal aorta is significantly stenosed as well as the proximal parts of the accessory renal arteries. Significant stenosis in the proximal part of the AMS. From the L3 level the infrarenal abdominal aorta is occluded as is the AIC bill. Left subclavian artery  in the prevertebral part shows subocclusion  and occlusion in a segment of 2 cm long; significant stenosis of the ostium of the left vertebral artery.D. Klarić et al. Generalized atherosclerosis, metabolic syndrome, and resistant hypertensionActa Clin Croat, Vol. 60, (Suppl. 1) 2021 11We also investigated the possibility of OSA sy, but ac-cording to his results on the Epworth scale (3) and heteroanamnesis, we discarded it.Considering all his comorbidities, we prescribed ACE inhibitor in therapy in a higher dose than he had before, CCB in maximum dose, thiazide as a diuretic for a better metabolic profile, and a low dose of MRA-spi-ronolactone, checking kidney function (eGFR) regularly.DiscussionLong-term metabolic syndrome is a significant factor in cardiovascular risk with the presence of resis-tant hypertension, high-grade renal failure, and ne-phrotic proteinuria with its consequences (decreased GFR- 34-31 ml/min, nephrotic syndrome - 4.37 g/dU, elevated cholesterol 6.0 mmol/L, LDL 3.61 mmol/L, triglycerides 2.61 mmol/L and unregulated blood sugar -16.6mmol/L)1,2,4. Despite the modifica-tion of antihypertensive therapy, ABPM still shows unregulated blood pressure. Initial endothelial damage at the level of the intima of the blood vessel, increased sympathetic activity, hyperglycemia, dyslipidemia, and many other proatherosclerotic factors lead to severe micro and macrovascular complications⁹. Peripheral occlusive artery disease (PAD) develops gradually and is clinically manifested with moderate to severe Ruth-eford’s grade IIa/IIb claudication. Subjective distur-bances are expressed as dull pain during physical work, long walks, standing, and exposure to cold. They usu-ally disappear while resting, but they can also appear as pronounced cramps at night at rest, indicating the ex-istence of neuropathy. Occasionally, ulcerations and gangrene are present on the peripheral parts of the lower extremities. Symptoms are usually reciprocal to the degree of morphological changes in the blood ves-sels. This problem is significantly more common in males with diabetes, dyslipidemia, hypertension, in-creased blood urate values, long-term smoking, and most of them also present coronary heart disease. Ath-erosclerotic changes are generalized with severe steno-ses of the aorta and many of its branches (Fig. 1). The consequences of these atherosclerotic changes are manifested in various organs and systems. In this case, it presents as ischemic heart disease with the need for PCI and valvular changes of MI, TI, chronic renal fail-ure, cerebrovascular, and peripheral arterial occlusive disease. Given the complex interaction of the compo-nents of metabolic syndrome and resistant hyperten-sion as well as the high prevalence in the therapeutic approach, the emphasis, in addition to aggressive anti-hypertensive, antidiabetic and hypolipemic therapy, should be on dietary measures and healthy lifestyle habits to prevent fatal consequences.ConclusionGiven the complex interrelationship of all its co-morbidities, male gender, and long-standing nicotinism, the question is which of these factors is the initial and causal driver of all consequences. Significant morpho-logical changes require a multidisciplinary approach with the necessary changes in lifestyle habits: smoking cessation, weight loss, restriction of salt and fat intake, moderate exercise, regulation of blood sugar, urate, and blood pressure, and the necessary invasive interventions.References1. Saklayen MG. The Global Epidemic of the Metabolic Syn-drome. Curr Hypertens Rep. 2018 Feb 26;20(2):12. doi: 10.1007/s11906-018-0812-z2. Després JP, Lemieux I. Abdominal obesity and metabolic syn-drome. Nature. 2006 Dec 14;444(7121):881-7. doi: 10.1038/nature054883. Damen JA, Hooft L, Schuit E, Debray TP, Collins GS, Tzou-laki I, et al. Prediction models for cardiovascular disease risk in the general population: systematic review. BMJ. 2016 May 16;353:i2416. doi: 10.1136/bmj.i24164. Kaczmarski KR, Sozio SM, Shafi T. Resistant hypertension and cardiovascular disease mortality in the US: results from National Health and Nutrition Examination Survey (NHANES). BMC Nephrol. 2019 Apr 25;20(1):138. doi: 10.1186/s12882-019-1315-05. Kuwabara M. Hyperuricemia, Cardiovascular Disease and Hy-pertension. Karger AG, Basel. 2016;May: 242-252.doi: 10.1159 /0004437696. Saxena T, Ozefa AA, Saxena M. Pathophysiology of essential hypertension: an update. Expert review of Cardiovascular ther-apy 16.2018 Dec;16:879-8877. Kobori H, Nangaku M, Navar LG, Nishiyama A. The Intrare-nal Renin- Angiotensin System: From Physiology to the Pathobiology. Pharmacol Rev. 2007 Sep;59(3):251-87. doi: 10.1124/pr.59.3.38. Patel S, Abu-Izneid T. Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and patholo-gies. Biomed Pharmacother. 2017 Oct;94:317-325. doi: 10.1016/j.biopha.2017.07.0919. Libby P. Inflammation in Atherosclerosis. Arteriosclerosis, Thrombosis and Vascular Biology. 2012 Sep;32:2045-2051. doi.org/10.1161/ATVBAHA.108.179705D. Klarić et al. Generalized atherosclerosis, metabolic syndrome, and resistant hypertension12 Acta Clin Croat, Vol. 60, (Suppl. 1) 2021SažetakGENERALIZIRANA ATEROSKLEROZA, METABOLIČKI SINDROM  I REZISTENTNA HIPERTENZIJA – UZROCI I POSLJEDICED. Klarić, P. Grbić Pavlović i M. KlarićKomponente metaboličkog sindroma dovode do generaliziranih aterosklerotskih promjena te mikro i makrovaskularnih komplikacija s oštećenjem sustava i organa. Slijedom toga, liječenje bolesnika s posljedicama promjena na ciljnim organima vrlo je skupo, složeno i nepredvidljivo. Predstavljamo 65-godišnjeg pacijenta, dijabetičara, kojem je dijagnosticirana hiper-lipidemija, neregulirana arterijska hipertenzija u prisutnosti drugih komponenata metaboličkog sindroma i posljedično razvi-jene komplikacije generalizirane ateroskleroze. Unatoč detaljnoj, individualno prilagođenoj terapiji, u skladu s trenutnim preporukama, smatramo da je uspjeh liječenja vrlo usko povezan i ovisi o prehrambenim mjerama, zdravim životnim navi-kama i suradnji pacijenta.Ključne riječi: ateroskleroza; metabolički sindrom; bubrežna insuficijencija

Generalizirana ateroskleroza, metabolički sindrom i rezistentna hipertenzija - uzroci i posljedice

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