The Relationship Between Arteriosclerosis And Blood Pressure Progression And Its Impact On The Intensive Antihypertensive Effec

Part Ⅰ:Temporal relationship between arterial stiffness and systolic blood pressure:a cross-lagged analysisBackground:Systolic blood pressure(SBP)and arterial stiffness(AS)are two major independent predictors of cardiovascular disease(CVD).Both blood pressure(BP)and AS increase with advancing age and contribute to the substantial societal and economic burden of CVD.The temporal relationship between AS and SBP is controversial,and whether or not the temporal relationship between AS and SBP is affected by how strictly SBP is controlled has been unclear.In this study,we analyzed data from the STEP(Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients)trial to determine the temporal relationship between AS and SBP according to whether SBP control was intensive or standard(intensive,110 ≤ SBP<130 mmHg;standard,130 ≤ SBP<150 mmHg).Methods:This study included 5369 participants in the STEP trial for whom baseline and follow-up brachial-ankle pulse wave velocity(baPWV)data were complete.STEP was a randomized controlled trial that compared the effects of intensive and standard SBP control on cardiovascular outcomes in 8511 patients with hypertension at 42 clinical centers in China.Arterial stiffness was assessed by baPWV,patients were categorized by baseline baPWV(AS,baPWV≥ 1800 cm/s;non-AS,baPWV<1800 cm/s).Cross-lagged panel model(CLPM)is a longitudinal data statistics model used to explore the causal relationship.The temporal relationship between baPWV and SBP was assessed using a cross-lagged panel model.CLPM were performed in all patients and in those with intensive or standard SBP control respectively.Results:Data were analyzed for 5369 patients(mean age 66.01±4.69 years;54.07%women).Patients with AS at baseline were significantly less likely to achieve their target SBP than those without arterial stiffening in the intensive and standard treatment groups(65.17%vs 76.91%and 97.33%vs 98.96%,respectively,both P<0.05).The standardized regression coefficient from baseline baPWV to follow-up SBP was 0.05(95%confidence interval[CI]0.02-0.08,P<0.001)and that from baseline SBP to follow-up baPWV was insignificant from zero(β=-0.007,95%CI-0.03 to 0.02;P=0.62)after adjustment for confounders.The findings were similar in the intensive and standard treatment groups.The standard regression coefficient from baseline baPWV to follow-up SBP was 0.04(95%CI,0.0003-0.08;P<0.05)in the intensive treatment group and 0.07(95%CI,0.03-0.11)in the standard treatment group and that from baseline SBP to follow-up baPWV was insignificant from zero in both groups(intensive,β=-0.01[95%CI,-0.05 to 0.03];P=0.62;standard,β=-0.003[95%CI,-0.04 to 0.03];P=0.15)after adjustment for confounders.Conclusions:Arterial stiffening consistently preceded SBP in the intensive and standard groups,and compared with patients in non-AS group at baseline,patients with AS had difficulty in reaching of target SBP,particularly in the intensive treatment group.Part Ⅱ:Influence of baseline arterial stiffness on effects of intensive compared with standard blood pressure controlBackground:Arterial stiffness(AS),a characteristic feature of aging arteries,is an independent age-related risk factor for stroke,coronary heart disease,and all-cause death in patients with hypertension.AS and hypertension frequently coexist,particularly in older patients.Emerging evidence has proven the benefit of intensive systolic blood pressure(SBP)control among patients with hypertension,however,whether the benefit effect of intensive versus standard SBP treatment(intensive,1 10 ≤ SBP<130 mmHg;standard,130≤SBP<150 mmHg)is different in patients with and without AS is unclear.This study aims to investigate the interaction between the baseline AS and SBP treatments on cardiovascular outcomes.Methods:This study based on the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients(STEP)trial.We involved 6865 participants with complete data regarding baseline brachial-ankle pulse wave velocity(baPWV).Patients were categorized by baseline AS status(AS,baPWV≥ 1800 cm/s;non-AS,baPWV<1800 cm/s).The primary outcome was a composite of the first occurrence of stroke,acute coronary syndrome(ACS),acute decompensated heart failure,coronary revascularization,atrial fibrillation,or death of cardiovascular causes.The secondary outcomes were stroke,ACS,major cardiovascular events(MACE),and all-cause death.Cox regression was used to calculate hazard ratios for the outcomes.The Fine-Gray subdistribution hazard model was used to calculate the hazard ratios for the primary outcome and secondary outcomes associated with intensive SBP treatment versus standard SBP treatment(reference)among participants in the AS or non-AS group.Cox regression model was used to calculate the hazard ratios for all-cause death.P for interaction was used to investigate the interaction effect of the SBP treatment group in patients with AS and non-AS.Results:A total of 6865 patients were included in this study(mean age,66.14± 4.75 years;53.55%female).During a mean follow-up of 2.69 years,248 primary outcome events and 81 all-cause deaths occurred.The hazard ratios for the primary outcome were 0.76(95%confidence interval(CI),0.54-1.09)and 0.63(95%CI,0.43-0.92)in the AS and non-AS groups,respectively(P for interaction=0.43),and that for stroke was 0.58(95%CI,0.331.02)and 0.48(95%CI,0.23-0.99)in the AS and non-AS groups,respectively(P for interaction=0.68).Effects of intensive SBP treatment on all-cause death and safety outcomes were also similar in the two groups(P for interaction>0.05 for all).Conclusions:Among patients at 60 to 80 years of age with hypertension,the beneficial effects of an intensive SBP target of 110 to 130 mmHg compared with a standard SBP target of 130 to 150 mm Hg on cardiovascular events were similar among those in AS group and non-AS group.