Μελέτη της επίδρασης των στατινών επί των φλεγμονώδων δεικτών σε αλατοευαίσθητους και μη υπερτασικούς ασθενείς

Abstract

Background and purpose: Increased salt intake is thought to be associated withhypertension development, while it contributes to the increased cardiovascular risk thataccompanies salt sensitivity. Arterial hypertension is characterized by endothelialdysfunction, which plays a pivotal role in the pathogenesis of atherosclerosis. Statin usehas contributed significantly to the reduction of the morbidity and mortality ofcardiovascular disease, through both their lipid lowering and pleiotropic actions. The aimof the present study was to investigate whether the administration of simvastatin for 4weeks has any favorable effects in levels of diverse markers of inflammatory activation insalt-sensitive and salt-resistant essential hypertensive patients.Methods: The entire population consisted of 40 consecutive newly-diagnosed untreatedpatients with essential hypertension stage I-II (25 men, mean age=50 years, office bloodpressure=150/96 mmHg). Based on the protocol for assessment of salt sensitivity and thechange in 24h mean arterial pressure (ǻMAP) between the high-sodium and the lowsodiumperiods, patients were divided into two groups: those with salt sensitivity (ǻMAP ≥Ν8mmHg, n=16) and those with salt resistance (ǻMAP < 8mmHg, n=24). Moreover, bloodsamples were collected for the determination of the metabolic profile and hs-CRP, sICAM-1, sVCAM-1 țαȚ MCP-1 levels. Simvastatin 40 mg/day was administered for 4 weeksfollowed by measurement of 24h ABPM and determination of the metabolic profile andthe levels of the inflammatory markers.Results: The two groups did not differ regarding age, sex, smoking, body mass index,waist circumference, blood glucose, urea, creatinine, uric acid, estimated glomerularfiltration rate, urine albumin to creatinine ratio, liver function and lipid profile (p=NS).Salt-sensitive patients compared to salt-resistant were characterized by higher baselinelevels of log hs-CRP (0.46±0.16 vs 0.21±0.29 mg/L, p=0.001), MCP-1 (91.9±17.6 vs68.8±13.7 pg/ml, p<0.0005) and sVCAM-1 (875.7±66.6 vs 732.5±190.8 ng/ml, p=0.002),while did not differ regarding levels of sICAM-1 (297.4±20.6 vs 288.6±49.2 ng/ml,p=0.440). Administration of simvastatin for 4 weeks in salt-sensitive subjects led tostatistically significant reduction of log hs-CRP (0.14±0.22 vs 0.46±0.16 mg/L, p<0.0005),hs-CRP in absolute values [1.43 (0.80-2.11) vs 3.08 (1.95-4.08), p<0.0005], MCP-1(79.8±15.1 vs 91.9±17.6 pg/ml, p<0.0005) țαȚ sVCAM-1 (712.4±80.3 vs 875.7±66.6ng/ml, p<0.0005). Moreover, in salt-resistant subjects statin treatment was related tostatistically significant reduction of log hs-CRP (0.04±0.34 vs 0.21±0.29 mg/L, p<0.0005), hs-CRP in absolute values [1.20 (0.60-2.28) vs 1.85 (1.00-2.97), p<0.0005], and MCP-1(60.8±12.6 vs 68.8±13.7 pg/ml, p<0.0005). Evaluating the impact of the intervention onlevels of inflammatory markers, the eta squared statistic (eta squared >0.14), indicated alarge effect size for both groups, being greater for the salt-sensitivity group. Within theentire population as well as the two studied subgroups, the treatment-related reductions inlevels of inflammatory markers were not significantly correlated to the concomitant statininducedreduction in total serum cholesterol or LDL cholesterol (p=NS).Conclusions: In newly-diagnosed untreated patients with essential hypertension,administration of simvastatin for 4 weeks led to statistically significant reduction in levelsof hs-CRP, MCP-1 and sVCAM-1 in both subgroups of salt-resistant and salt-sensitivesubjects, being greater in the latter. The findings of our study contribute to the furtherunderstanding of the pleiotropic mechanisms of statins and the importance of saltsensitivity in the setting of hypertension.