Korelacija ultrazvučnih karakteristika ateroskleroze karotidnih arterija i prisustva kardiometaboličkih faktora rizika kod bolesnika sa ishemijskim moždanim udarom

Abstract

UVOD: Ateroskleroza je najčešća bolest karotidnih arterija i uzrok je oko 20% svih ishemijskih moždanih udara (IMU). Osim stepena stenoze i određene karakteristike karotidnog plaka označavaju povišen rizik za IMU. Ultrazvukom je moguće pouzdano evaluirati aterosklerotske promene na karotidnim arterijama. Iako su faktori rizika (FR) za aterosklerozu istovremeno i FR za IMU, prisustvo identičnih FR kod pacijenata sa IMU, ne znači i prisustvo istog stepena ateroskleroze na karotidnim arterijama. CILJ: Utvrđivanje povezanosti pojedinih ultrazvučnih karakteristika karotidne ateroskleroze, sa prisustvom različitih kardiometaboličkih FR i njihovih biomarkera, kod pacijenata sa IMU. MATERIJAL I METODE: U istraživanje je uključeno 120 pacijenata sa nekardioembolijskim IMU u karotidnom slivu koji su podeljeni u dve grupe; 60 sa lakunarnim i 60 sa nelakunarnim infarktom mozga. Svim pacijentima je određivano prisustvo FR, kao što su hipertenzija, dijabetes, hiperlipoproteinemija, pušenje, gojaznost, metabolički sindrom, hiperhomocisteinemija i inflamacija. Beležene su vrednosti krvnog pritiska, glikemije, glikoliziranog hemoglobina, parametara lipidskog statusa, apolipoproteina (Apo) A-I i B, lipoproteina a, indeksa telesne mase (BMI), homocisteina, C reaktivnog proteina (CRP). Pomoću karotidnog dupleks ultrazvuka određivane su vrednosti intima-medijalnog zadebljanja (IMT), morfologija plaka, površina plaka, stepen stenoze. Demografske karakteristike, FR i njihovi biomarkeri, te ultrazvučne karakteristike karotidne ateroskleroze, poređene su između dve grupe pacijenata. Korišćeni su hi-kvadrat test i t-test. Korelacije FR i vrednosti njihovih biomarkera sa različitim karakteristikama karotidnog plaka, određivane su upotrebom Pearsonovog koeficijenta korelacije r i Kramerovog V. Upotrebom regresionih analiza ispitivan je prediktivni značaj određenih FR i njihovih biomarkera u pojavi pojedinih karakteristika karotidnog plaka. REZULTATI: Više pacijenata sa lakunarnim infarktom je imalo hipertenziju (98.3% naspram 85%; p=0.021). Pacijenti sa lakunarnim infarktom imali su veće vrednosti BMI (27.6 kg/m2 naspram 25.9 kg/m2; p=0.029), dok su pacijenti sa nelakunarnim infarktom imali veće vrednosti CRP (16.4 mg/l naspram 6.8 mg/l; p=0.001). Demografske karakteristike, ostali FR i njihovi biomarkeri, kao i vrednosti karotidnog IMT se nisu značajno razlikovali između dve grupe pacijenata. Pacijenti sa nelakunarnim infarktom su imali veći stepen karotidne stenoze (79.7% naspram 33.2%; p=0,0001), kao i češće prisustvo heterogenog plaka (73.3% naspram 35%; p<0,001), hipoehogenog plaka (51.7% naspram 16.7%; p<0.001) i neravnog plaka (81.7% naspram 21.7%; p<0,001). Sa vrednostima IMT značajno (p<0.05) su korelirali životna dob pacijenata (r=0.276), dijabetes (Cramerovo V=0.236), metabolički sindrom (Cramerovo V=0.247), HDL holesterol (r=-0.254), LDL/HDL (r=0.306), ApoA-I (r=-0.386) i ApoB/ApoA-I (r=0.359). Sa prisustvom heterogenog plaka su korelirali metabolički sindrom (Cramerovo V=0.246), ApoB (r=0.213), ApoB/ApoA-I (r=0.207) i povišen CRP (Cramerovo V=0.266). Sa neravnom površinom plaka značajno je korelirao povišen CRP (Cramerovo V=0.283). Sa stepenom stenoze značajno su korelirali BMI (r=-0.180) i povišen CRP (Cramerovo V=0.301). Nezavisni prediktori povišenih vrednosti IMT bili su starija životna dob pacijenata (β=0.230; p=0.006), ApoA-I (β=-0.244; p=0.008) i ApoB/ApoA-I (β=0.247; p=0.007). Prediktori prisustva heterogenog plaka bili su muški pol (p=0.011; OR=3.425), ApoB (p=0.007; OR=8.972), BMI (p=0.0001; OR=0.380), metabolički sindrom (p=0.003; OR=4.555) i povišen CRP (p=0.018; OR=2.800). Prediktori prisustva hipoehogenog plaka bili su ApoB (p<0.001; OR=29.2), BMI (p=0.02; OR=0.514), metabolički sindrom (p<0.001; OR=9.224) i povišen CRP (p=0.046; OR=2.659). Povišen CRP bio je jedini prediktor prisustva neravnog plaka (p=0.002; OR=3.203), kao i prisustva većeg stepene karotidne stenoze (β=0.270; p=0.002). ZAKLJUČAK: Iako je karotidna stenoza znatno zastupljenija među pacijenatima sa nelakunarnim nego lakunarnim nekardioembolijskim IMU, prisustvo kardiometaboličkih FR, njihovih biomarkera i vrednosti IMT se bitno ne razlikuje između ove dve grupe pacijenata. Osim stenoze i prisustvo heterogenog, hipoehogenog i neravnog karotidnog plaka nosi povišen rizik za IMU. Među FR i njihovim biomarkerima ApoA-I i ApoB su najbolji prediktori karotidne ateroskleroze. Apolipoprotein B i metabolički sindrom su najjače povezani sa prisustvom heterogenog i hipoehogenog plaka. Povišen CRP kod pacijenata sa akutnim IMU može biti znak destabilizacije plaka i ukazivati na prisustvo signifikantne karotidne stenoze.

INTRODUCTION: Atherosclerosis is the most common disease of carotid arteries, causing 20% of all ischemic strokes. Besides the degree of stenosis, certain characteristics of carotid plaques indicate an increased risk for stroke. Carotid ultrasound can reliably evaluate atherosclerotic changes in carotid arteries. Although the risk factors for atherosclerosis are the same as the risk factors for stroke, the presence of identical risk factors in patients with stroke does not necessarily mean the presence of the same degree of carotid atherosclerosis. AIM: To determine correlation of certain characteristics of carotid atherosclerosis detected by ultrasound with the presence of various cardiometabolic risk factors in patients with ischemic stroke. METHODS: The study included 120 patients with noncardioembolic ischemic stroke in the anterior circulation, who were divided into two groups; 60 with lacunar and 60 with nonlacunar brain infarction. The presence of cardiometabolic risk factors, such as hypertension, diabetes, hyperlipoproteinemia, smoking, obesity, metabolic syndrome, hyperhomocysteinemia, and inflammation, was evaluated in all patients. Data regarding blood pressure, glycemia, glycated hemoglobin, lipid status parameters, apolipoprotein (ApoAI and ApoB), lipoprotein a, body mass index (BMI), homocysteine, and C-reactive protein (CRP) were collected. Intima-media thickness (IMT), carotid plaque characteristics (morphology, surface) and the degree of stenosis were determined by carotid duplex ultrasound. Demographic characteristics, risk factors, biomarkers, as well as ultrasound characteristics of carotid atherosclerosis, were compared between patients with lacunar and nonlacunar stroke. Two-sample student t-test and χ2 test were used for comparisons. In order to assess the correlation of various risk factors and their biomarkers with different characteristics of carotid plaques, we used the Pearson correlation coefficient r and Cramer's V. Regression analysis was used to evaluate the association of risk factors and their biomarkers with various carotid atherosclerosis characteristics. RESULTS: More patients with lacunar stroke had hypertension (98.3% vs. 85%; p=0.021). Patients with lacunar stroke had higher BMI values (27.6 kg/m2 vs. 25.9 kg/m2; p=0.029), while patients with nonlacunar stroke had higher CRP values (16.4 mg/l vs. 6.8 mg/l; p=0.001). Demographic characteristics, other risk factors and their biomarkers, as well as carotid IMT were not significantly different between the two groups of patients. Patients with nonlacunar stroke had a higher degree of carotid stenosis (79.7% vs. 33.2%; p=0.0001) and a higher prevalence of heterogeneous plaques (73.3% vs. 35%; p<0.001), hypoechogenic plaques (51.7% vs. 16.7%; p<0.001), and plaques with irregular surface (81.7% vs. 21.7%; p<0,001). IMT was significantly (p<0.05) correlated with the age of patients (r=0.276), diabetes (Cramer’s V=0.236), metabolic syndrome (Cramer’s V=0.247), HDL cholesterol (r=-0.254), LDL/HDL (r=0.306), ApoA-I (r=-0.386) and ApoB/ApoA-I (r=0.359). The presence of a heterogeneous plaque was correlated with metabolic syndrome (Cramer’s V=0.246) ApoB (r=0.213), ApoB/ApoA-I (r=0.207) and elevated CRP (Cramer’s V=0.266). A plaque with irregular surface was correlated with elevated CRP (Cramer’s V=0.283). The degree of carotid stenosis was correlated with BMI (r=-0.180) and elevated CRP (Cramer’s V=0.301). The independent predictors of higher values of IMT were older age (β=0.230; p=0.006), ApoA-I (β=-0.244; p=0.008), and ApoB/ApoA-I (β=0.247; p=0.007). The predictors of the presence of a heterogeneous plaque were male gender (p=0.011; OR=3.425), ApoB (p=0.007; OR=8.972), BMI (p=0.0001; OR=0.380), metabolic syndrome (p=0.003; OR=4.555) and elevated CRP (p=0.018; OR=2.800). The predictors of the presence of a hypoechogenic plaque were ApoB (p<0.001; OR=29.2), BMI (p=0.02; OR=0.514), metabolic syndrome (p<0.001; OR=9.224) and elevated CRP (p=0.046; OR=2.659). Elevated CRP was the only independent predictor of a plaque with irregular surface (p=0.002; OR=3.203) and of a higher degree of carotid stenosis (β=0.270; p=0.002). CONCULSIONS: Although carotid stenosis is significantly more pronounced in patients with nonlacunar than those with lacunar noncardioembolic ischemic stroke, cardiometabolic risk factors, their biomarkers and carotid IMT do not differ significantly between the two groups of patients. In addition to stenosis, a presence of heterogeneous, hypoechogenic and irregular-surface carotid plaques indicates an increased risk for ischemic nonlacunar stroke. Among the cardiometabolic risk factors and their biomarkers, ApoAI and ApoB have the strongest association with carotid atherosclerosis. Apolipoprotein B and metabolic syndrome have the strongest association with a heterogeneous and hypoechogenic carotid plaque. Elevated CRP in patients with acute ischemic stroke may be a sign of carotid plaque destabilization and can indicate a significant carotid stenosis.