Ten-year follow-up of very-high risk hypertensive patients undergoing renal sympathetic denervation.

OBJECTIVES: Renal denervation (RDN) has been proven to be effective in lowering blood pressure (BP) in patients, but previous studies have had short follow-ups and have not examined the effects of RDN on major cardiovascular outcomes. This study aimed to demonstrate the effectiveness and safety of RDN in the long-term treatment of hypertension and to determine if it has an effect on cardiovascular outcomes. METHODS: All patients with resistant hypertension who underwent RDN between 2011 and 2015 at Tianjin First Central Hospital were included in the study. Patients were followed up at 1,5 and 10 years and the longest follow-up was 12 years. Data were collected on office BP, home BP, ambulatory BP monitoring (ABPM), renal function, antihypertensive drug regimen, major adverse events (including acute myocardial infarction, stroke, cardiovascular death and all cause death) and safety events. RESULTS: A total of 60 participants with mean age 50.37 ±â€Š15.19 years (43.33% female individuals) completed long-term follow-up investigations with a mean of 10.02 ±â€Š1.72 years post-RDN. Baseline office SBP and DBP were 179.08 ±â€Š22.05 and 101.17 ±â€Š16.57 mmHg under a mean number of 4.22 ±â€Š1.09 defined daily doses (DDD), with a reduction of -35.93/-14.76 mmHg as compared with baseline estimates ( P  < 0.0001). Compared with baseline, ambulatory SBP and DBP after 10-years follow-up were reduced by 14.31 ±â€Š10.18 ( P  < 0.001) and 9 ±â€Š4.35 ( P  < 0.001) mmHg, respectively. In comparison to baseline, participants were taking fewer antihypertensive medications ( P  < 0.001), and their mean heart rate had decreased ( P  < 0.001). Changes in renal function, as assessed by estimated glomerular filtration rate (eGFR) and creatinine, were within the expected rate of age-related decline. No major adverse events related to the RDN procedure were observed in long-term consequences. All-cause mortality and cardiovascular mortality rates were 10 and 8.34%, respectively, for the 10-year period. CONCLUSION: The BP-lowering effect of RDN was safely sustained for at least 10 years post-procedure. More importantly, to the best of my knowledge, this is the first study to explore cardiovascular and all-cause mortality at 10 years after RDN.

[The effect of catheter based renal synthetic denervation on renin-angiotensin-aldosterone system in patients with resistant hypertension].

OBJECTIVE: to explore the effect of catheter based renal synthetic denervation on renin-angiotensin-aldosterone system (RAAS) and blood pressure reduction in patients with resistant hypertension. and assess the validity and security of the treatment. METHODS: Ten patients with resistant hypertension from June 2011 to December 2011 were retrospectively reviewed, and then all of 10 patients screened for eligibility were allocated to renal denervation. Primary endpoints were changes of office blood pressure at 1 week, 1, 3 and 6 months after procedure. We assessed the effectiveness of renal sympathetic denervation with heart rate (HR), renin activity (PRA), angiotensin II (AngII), aldosterone (Ald), and creatinine (Cr) before and 2 weeks after procedure. RESULTS: Office blood pressure after catheter-based renal denervation decreased by 22.8/9.1 mm Hg (1 mm Hg = 0.133 kPa), 34.8/14.7 mm Hg, 42.6/20.7 mm Hg, 43.2/21.6 mm Hg, at 1 week, 1, 3 and 6 months, respectively (P < 0.001). Meanwhile, the level of PRA, AngII, Ald decreased by (1.11 ± 0.89) ng×ml(-1)×h(-1) (P = 0.003), (17.06 ± 13.82) ng/L (P = 0.004), (404.5 ± 285.8) ng/L (P = 0.002), respectively; and heart rate decreased by 5.1 bpm (P = 0.002). However, the Cr level and eGFR did not change significantly (P > 0.05). CONCLUSION: Catheter-based renal sympathetic denervation can reduce the level of renin activity, angiotensin II and aldosterone, and causes substantial and sustained blood-pressure reduction.

[Association of tryptophan hydroxylase gene A218C and serotonin transporter gene polymorphism with essential hypertension in Chinese northern Han population].

OBJECTIVE: To investigate the relationship between tryptophan hydroxylase (TPH) gene A218C in intron 7 and 5-hydroxytryptamine transporter (5-HTT) gene variable number tandem repeat (VNTR) in intron 2 and gene-linked polymorphic region (LPR) deletion/insertion polymorphism and essential hypertension (EH) in Chinese northern Han population. METHODS: A total of 280 EH patients and 200 normotensive controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: There were no significant differences in the frequencies of the genotypes and alleles of TPH gene A218C and 5-HTTVNTR between EH patents and controls (all P > 0.05). The genotype frequencies of SS, LS and LL in the 5-HTTLPR polymorphism was 68%, 29% and 3% in EH patients, 53%, 37% and 10% in the controls respectively (P < 0.01). The frequencies of allele S and L of the 5-HTTLPR were 82% and 18% in EH patients, 72% and 28% in the controls respectively (P < 0.01). Compared with the carriers of L allele (LS + LL), the EH risk was significantly higher in the SS homozygote (OR = 1.90, 95%CI = 1.31 - 2.77, P = 0.001). After adjustment of age, gender, body mass index, blood lipids, fasting blood glucose and blood uric acid level, the binary logistic regression analysis demonstrated that SS genotype in the 5-HTTLPR polymorphism was significantly related to occurrence of EH (OR = 1.47, 95%CI = 1.06 - 2.04, P = 0.021). CONCLUSIONS: The SS genotype of the 5-HTTLPR might be a susceptible gene to EH, while the TPH gene A218C and 5-HTTVNTR polymorphism is not associated with EH in Chinese northern Han population.

[Association of serotonin transporter gene linked polymorphic region polymorphism with early onset myocardial infarction and platelet membrane glycoprotein I b].

OBJECTIVE: To investigate the association of serotonin transporter gene linked polymorphic region (5-HTTLPR) insertion/deletion polymorphism with early onset myocardial infarction(MI) and platelet membrane glycoprotein I b(GP I b) in Northern Han population of China. METHODS: A total of 150 patients with early onset MI and 150 age- and sex-matched controls with negative coronary arteriography were genotyped for the 5-HTTLPR polymorphism by using a polymerase chain reaction-based technique. The percentage of positive platelet membrane GP I b and the average fluorescence intensity were quantified by flow cytometry. RESULTS: The genotype frequencies of LL, LS and SS in the 5-HTTLPR were 32%, 47% and 21% in the MI patients, 17%, 43% and 39% in the controls respectively(P<0.01). The L allele frequency in the MI patients was significantly higher than that of the control group (56% vs 39%, P<0.01). The percentage of positive platelet membrane GP I b and the fluorescence intensity in subjects with LL homozygote were markedly lower than that of LS and SS genotypes in the MI and control groups (all P<0.01). Multivariate logistic regression analysis showed that the 5-HTTLPR LL genotype was independently related to the occurrence of early onset MI(OR was 1.961, P was 0.037). CONCLUSION: The LL genotype of the 5-HTTLPR might be associated with the susceptibility to developing early MI in Northern Han population of China. The platelet activation is increased in individuals of LL genotype.

[Intravascular ultrasonic evaluation of poststenting atherosclerotic plaque redistribution and lumen reduction at the stent edge: does stent length matter?].

OBJECTIVE: To evaluate the association between poststenting atherosclerotic plaque redistribution/lumen reduction at the stent edge and stent length. METHODS: Seventy stents were implanted to 47 patients with stable or unstable angina and 33 stents were < or = 18 mm and 37 stents were > 18 mm. Intravascular ultrasound analysis was performed on proximal stent edge, stent area and distal stent edge. Lumen area (LA) and vascular area (VA) were measured and lumen volume (LV) and vascular volume (VV) were calculated on the three segments. Vascular wall volume (WV) was calculated as VV-LV, volume of plaque redistribution = poststenting WV-prestenting WV. RESULTS: Compared to prestenting, poststenting LV significantly decreased, VV remained unchanged and WV significantly increased at proximal and distal edges of < or = 18 mm group and at proximal edge of > 18 mm group, suggesting reduced lumen due to plaque distribution. At distal edge of > 18 mm group, poststenting LV, VV and WV all equally significantly increased therefore the lumen was not affected by plaque distribution. CONCLUSION: The poststenting lumen changes due to plaque redistribution were associated with stent length, lumen reduced at proximal and distal edge of short stents and proximal edge of long stents but not at the distal edge of long stents.

Study on the interrelationship between 5-HTTLPR/G-protein beta3 subunit (C825T) polymorphisms and depressive disorder.

OBJECTIVE: To assess whether the promoter region of the serotonin transporter gene (5-HTTLPR) and G-protein beta3-subunit (GNbeta3 C825T) polymorphisms are associated with depressive disorder and explore the genetic mechanism concerning the pathogenesis of this disorder. METHODS: The genotypes were determined with polymerase chain reaction and allele-specific restriction enzyme analysis. Patients suffering from depression (n=184) and sex and age-matched controls (n=158) were compared in this study. RESULTS: The frequencies of 5-HTTLPR SS and GNbeta3 825TT genotypes and 5-HTTLPR S and GNbeta3 825T alleles in patients suffering from depression were significantly higher than those in the controls (P<0.01). Combined genotype analysis showed that individuals with both 5-HTTLPR S and GNbeta3 825T alleles (odds ratio=3.25, P=0.002) had a risk of depressive disorder higher than those with 5-HTTLPR S (odds ratio=1.817, P=0.01) or GNbeta3 825T alleles (odds ratio=2.214, P=0.001) alone. CONCLUSIONS: These results indicated that the etiology of depressive disorder is associated with 5-HTTLPR and GNbeta3 C825T polymorphisms. Our data also suggests that an interaction effect may exist between the 5-HTTLPR S allele and GNbeta3 825T allele in increasing the risk of depressive disorder.

[Intravascular ultrasound study of coronary remodeling and determination of matrix metalloproteinase and hypersensitive C-reactive protein].

OBJECTIVE: To investigate remodeling characteristics of coronary lesions in patients with acute coronary syndromes (ACS) versus stable angina pectoris (SA) using intravascular ultrasound (IVUS), and to explore the relationship between arterial remodeling and clinical presentation or matrix metalloproteinase (MMPs) or hyper-sensitive C-reactive protein (hs-CRP). METHODS: We studied culprit lesions of 38 patients with ACS and 18 patients with SA using IVUS before coronary intervention. The lesion site and a proximal or distal reference site including the external elastic membrane (EEM) area and lumen area were analyzed. Plaque area and remodeling index (RI) were calculated, and directions of arterial remodeling were determined. Positive remodeling was defined as RI > 1.05 and negative remodeling as RI < 0.95. We analyzed the culprit lesion qualitatively, identified high risk plaque and compared them in each group. The blood level of MMP-2, MMP-9 and hs-CRP in each group were also determined. RESULTS: The plaque area at culprit lesions in patients with ACS was significantly larger (11.94 +/- 4.90 versus 9.17 +/- 3.36 mm2; P = 0.035), and also the RI in ACS group was significantly greater than that of patients with SA (0.972 +/- 0.222 versus 0.796 +/- 0.130; P = 0.003). The distribution of remodeling in these two groups was different: positive remodeling was more frequent in ACS group than in SA group (34.2% versus 5.6%, P = 0.047), whereas negative remodeling was more frequent in SA group (52.6% versus 88.9%, P = 0.003). There was higher incidence of high risk plaque in ACS group compared to SA (76.3% versus 50.0%, P = 0.040). The level of serum MMP-2 in ACS group was higher than that of SA group (250.65 +/- 47.97 microg/L versus 214.21 +/- 47.20 microg/L, P = 0.029). The same applied for plasma MMP-9 (84.26 +/- 9.78 microg/L versus 68.46 +/- 22.82 microg/L, P = 0.038) and serum hs-CRP (3.62 +/- 3.37 mg/L versus 1.48 +/- 1.52 mg/L, P = 0.041). CONCLUSIONS: Positive remodeling, larger plaque area and higher incidence of high risk plaque are associated with ACS, whereas negative remodeling is more common in patients with SA. This association between the extent of remodeling and clinical presentation may reflect a greater tendency that plaques with positive remodeling can cause ACS. The change of level of MMP-2, MMP-9 and hs-CRP in ACS patients may be helpful in investigating vulnerable plaques.

[Further study on the indexes of auxiliary laboratory diagnosis in the syndrome of hyperactivity of liver-yang].

The indexes of auxiliary laboratory diagnosis, including plasma norepinephine (NE) levels, plasma epinephrine (E) levels, mean blood flow velocity of the middle cerebral artery (MCA-Vm) and systolic blood flow velocity of the middle cerebral artery (MCA-Vs), were observed in patients with the syndrome of hyperactivity liver-yang. The results indicated that the levels of the 4 indexes were significantly higher in the patients with the syndrome of hyperactivity liver-yang than those in the controls. In hypertension patients with the syndrome of hyperactivity liver-yang, there was a positive correlation between symptomatic scores of the syndrome of hyperactivity liver-yang and diastolic pressure (Pd), plasma NE and E levels. The symptoms ameliorated, and the levels of the 4 indexes decreased correspondingly in 3 weeks after the treatment of Qianyangfang (a traditional Chinese herb).