Different components of blood pressure are associated with increased risk of atherosclerotic cardiovascular disease versus heart failure in advanced chronic kidney disease.
ABSTRACT: Blood pressure is a modifiable risk for cardiovascular disease (CVD). Among hemodialysis patients, there is a U-shaped association between blood pressure and risk of death. However, few studies have examined the association between blood pressure and CVD in patients with stage 4 and 5 chronic kidney disease. Here we studied 1795 Chronic Renal Insufficiency Cohort (CRIC) Study participants with estimated glomerular filtration rate <30 ml/min per 1.73 m2 and not on dialysis. The association of systolic (SBP), diastolic (DBP), and pulse pressure with the risk of physician-adjudicated atherosclerotic CVD (stroke, myocardial infarction, or peripheral arterial disease) and heart failure was tested using Cox regression adjusted for demographics, comorbidity and medications. There was a significant association with higher SBP (adjusted hazard ratio 2.04 [95% confidence interval: 1.46-2.84]) for SBP over 140 vs under 120 mmHg, higher DBP (2.52 [1.54-4.11]) for DBP >90 mm Hg versus <80 mm Hg and higher pulse pressure (2.67 [1.82-3.92]) for pulse pressure >68 mm Hg versus <51 mm Hg with atherosclerotic CVD. For heart failure, there was a significant association with higher pulse pressure only (1.42 [1.05-1.92]) for pulse pressure >68 mm Hg versus <51 mmHg, but not for SBP or DBP. Thus, among participants with stage 4 and 5 chronic kidney disease, there was an independent association between higher SBP, DBP, and pulse pressure with the risk of atherosclerotic CVD, whereas only higher pulse pressure was independently associated with a greater risk of heart failure. Further trials are needed to determine whether aggressive reduction of blood pressure decreases the risk of CVD events in patients with stage 4 and 5 chronic kidney disease.
Project description:BACKGROUND:Current guidelines recommend treating hypertension in patients with peripheral artery disease (PAD) to reduce the risk of cardiac events and stroke, but the effect of reducing blood pressure on lower extremity PAD events is largely unknown. We investigated the association of blood pressure with lower extremity PAD events using data from the ALLHAT trial (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). METHODS:ALLHAT investigated the effect of different antihypertensive medication classes (chlorthalidone, amlodipine, lisinopril, or doxazosin) on cardiovascular events. With the use of these data, the primary outcome in our analysis was time to first lower extremity PAD event, defined as PAD-related hospitalization, procedures, medical treatment, or PAD-related death. Given the availability of longitudinal standardized blood pressure measurements, we analyzed systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure as time-varying categorical variables (reference categories 120-129 mm?Hg for SBP, 70-79 mm?Hg for DBP, and 45-54 mm?Hg for pulse pressure) in separate models. We used extended Cox regression with death as a competing risk to calculate the association of each blood pressure component with PAD events, and report the results as subdistribution hazard ratios and 95% CIs. RESULTS:The present analysis included 33?357 patients with an average age of 67.4 years, 53.1% men, 59.7% white race, and 36.2% with diabetes mellitus. The median baseline blood pressure was 146/84 mm?Hg. Participants were followed for a median of 4.3 (interquartile range, 3.6-5.3) years, during which time 1489 (4.5%) had a lower extremity PAD event, and 4148 (12.4%) died. In models adjusted for demographic and clinical characteristics, SBP <120 mm?Hg was associated with a 26% (CI, 5%-52%; P=0.015) higher hazard and SBP?160 mm?Hg was associated with a 21% (CI, 0%-48%; P=0.050) higher hazard for a PAD event, in comparison with SBP 120 to 129 mm?Hg. In contrast, lower, but not higher, DBP was associated with a higher hazard of PAD events: for DBP <60 mm?Hg (hazard ratio, 1.72; CI, 1.38-2.16). Pulse pressure had a U-shaped association with PAD events. CONCLUSIONS:In this reanalysis of data from ALLHAT, we found a higher rate of lower extremity PAD events with higher and lower SBP and pulse pressure and with lower DBP. Given the recent revised blood pressure guidelines advocating lower SBP targets for overall cardiovascular risk reduction, further refinement of optimal blood pressure targets specific to PAD is needed. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov . Unique identifier: NCT00000542.
Project description:The association between within-visit variability of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and all-cause and cardiovascular (CVD) mortality was examined using the Third National Health and Nutrition Survey (n=15,317). Three SBP and DBP readings were taken by physicians during a single medical evaluation. Within-visit variability for each participant was defined using the standard deviation of SBP and DBP across these measurements. Mortality was assessed over 14 years (n=3848 and n=1684 deaths from all causes and CVD, respectively). After age, sex, and race-ethnicity adjustment, the hazard ratios (95% confidence intervals) for all-cause mortality associated with the 4 highest quintiles of within-visit standard deviation of SBP (2.00-2.99 mm Hg, 3.00-3.99 mm Hg, 4.00-5.29 mm Hg, and ≥5.30 mm Hg) compared with participants in the lowest quintile of within-visit standard deviation of SBP (<2.0 mm Hg) were 1.04 (0.87-1.26), 1.09 (0.92-1.29), 1.06 (0.88-1.28), and 1.13 (0.95-1.33), respectively (P=.136). The analogous hazard ratios for CVD mortality were 0.95 (0.69-1.32), 0.96 (0.67-1.36), 0.95 (0.74-1.23), and 1.04 (0.80-1.35), respectively (P=.566). No association with mortality was present after further adjustment and when modeling within-visit standard deviation of SBP as a continuous variable. Standard deviation of DBP was not associated with mortality.
Project description:BACKGROUND:The optimal systolic blood pressure (SBP) treatment goal is in question, with SPRINT (Systolic Blood Pressure Intervention Trial) suggesting benefit for 120 mm Hg. However, achieving an SBP this low may reduce diastolic blood pressure (DBP) to levels that could compromise myocardial perfusion. OBJECTIVES:This study sought to examine the independent association of DBP with myocardial damage (using high-sensitivity cardiac troponin-T [hs-cTnT]) and with coronary heart disease (CHD), stroke, or death over 21 years. METHODS:The authors studied 11,565 adults from the ARIC (Atherosclerosis Risk In Communities) cohort, analyzing DBP and hs-cTnT associations as well as prospective associations between DBP and events. RESULTS:Mean baseline age was 57 years, 57% of patients were female, and 25% were black. Compared with persons who had DBP between 80 to 89 mm Hg at baseline (ARIC visit 2), the adjusted odds ratio of having hs-cTnT ?14 ng/l at that visit was 2.2 and 1.5 in those with DBP <60 mm Hg and 60 to 69 mm Hg, respectively. Low DBP at baseline was also independently associated with progressive myocardial damage on the basis of estimated annual change in hs-cTnT over the 6 years between ARIC visits 2 and 4. In addition, compared with a DBP of 80 to 89 mm Hg, a DBP <60 mm Hg was associated with incident CHD and mortality, but not with stroke. The DBP and incident CHD association was strongest with baseline hs-cTnT ?14 ng/l (p value for interaction <0.001). Associations of low DBP with prevalent hs-cTnT and incident CHD were most pronounced among patients with baseline SBP ?120 mm Hg. CONCLUSIONS:Particularly among adults with an SBP ?120 mm Hg, and thus elevated pulse pressure, low DBP was associated with subclinical myocardial damage and CHD events. When titrating treatment to SBP <140 mm Hg, it may be prudent to ensure that DBP levels do not fall below 70 mm Hg, and particularly not below 60 mm Hg.
Project description:The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline lowered the threshold (systolic blood pressure [SBP] <130 mm Hg and diastolic blood pressure [DBP] ≥80 mm Hg) for isolated diastolic hypertension (IDH), whereas the 2018 Chinese guideline still recommends the old threshold (SBP <140 mm Hg and DBP ≥90 mm Hg). This study aimed to investigate the association between IDH, as defined by both guidelines, and the risk of incident cardiovascular disease (CVD) in rural areas of northeast China. This prospective study included participants whose baseline data were collected between 2004 and 2006. The exclusion criteria were baseline CVD, incomplete data, and systolic hypertension. The primary end point was incident CVD, a composite end point including nonfatal myocardial infarction (MI), nonfatal stroke, and CVD death. Multivariate Cox models were used to evaluate the association of IDH with CVD risk. The authors analyzed 19 688 participants (7140 participants with IDH) according to the ACC/AHA guideline. Compared with normotensive participants, individuals with ACC/AHA-defined IDH were at a high risk of CVD (HR = 1.177, 95% CI: 1.035-1.339). A similar difference in CVD risk was noted when normotensive participants were compared with those with IDH, determined based on the 2018 Chinese guideline (HR = 1.218, 95% CI: 1.050-1.413). Similar results were found in participants who did not take antihypertensives at baseline. Moreover, IDH defined by either guideline was significantly associated with nonfatal MI. ACC/AHA-defined IDH was associated with a risk of CVD, implying that blood pressure management should be improved in rural areas of China.
Project description:BACKGROUND:Data from before the 2000s indicate that the majority of incident cardiovascular disease (CVD) events occur among US adults with systolic and diastolic blood pressure (SBP/DBP) ?140/90 mm?Hg. Over the past several decades, BP has declined and hypertension control has improved. METHODS:We estimated the percentage of incident CVD events that occur at SBP/DBP <140/90 mm?Hg in a pooled analysis of 3 contemporary US cohorts: the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), the MESA (Multi-Ethnic Study of Atherosclerosis), and the JHS (Jackson Heart Study) (n=31?856; REGARDS=21?208; MESA=6779; JHS=3869). Baseline study visits were conducted in 2003 to 2007 for REGARDS, 2000 to 2002 for MESA, and 2000 to 2004 for JHS. BP was measured by trained staff using standardized methods. Antihypertensive medication use was self-reported. The primary outcome was incident CVD, defined by the first occurrence of fatal or nonfatal stroke, nonfatal myocardial infarction, fatal coronary heart disease, or heart failure. Events were adjudicated in each study. RESULTS:Over a mean follow-up of 7.7 years, 2584 participants had incident CVD events. Overall, 63.0% (95% confidence interval [CI], 54.9-71.1) of events occurred in participants with SBP/DBP <140/90 mm?Hg; 58.4% (95% CI, 47.7-69.2) and 68.1% (95% CI, 60.1-76.0) among those taking and not taking antihypertensive medication, respectively. The majority of events occurred in participants with SBP/DBP <140/90 mm?Hg among those <65 years of age (66.7%; 95% CI, 60.5-73.0) and ?65 years of age (60.3%; 95% CI, 51.0-69.5), women (61.4%; 95% CI, 49.9-72.9) and men (63.8%; 95% CI, 58.4-69.1), and for whites (68.7%; 95% CI, 66.1-71.3), blacks (59.0%; 95% CI, 49.5-68.6), Hispanics (52.7%; 95% CI, 45.1-60.4), and Chinese-Americans (58.5%; 95% CI, 45.2-71.8). Among participants taking antihypertensive medication with SBP/DBP <140/90 mm?Hg, 76.6% (95% CI, 75.8-77.5) were eligible for statin treatment, but only 33.2% (95% CI, 32.1-34.3) were taking one, and 19.5% (95% CI, 18.5-20.5) met the SPRINT (Systolic Blood Pressure Intervention Trial) eligibility criteria and may benefit from a SBP target goal of 120 mm?Hg. CONCLUSIONS:Although higher BP levels are associated with increased CVD risk, in the modern era, the majority of incident CVD events occur in US adults with SBP/DBP <140/90 mm?Hg. While absolute risk and cost-effectiveness should be considered, additional CVD risk-reduction measures for adults with SBP/DBP <140/90 mm?Hg at high risk for CVD may be warranted.
Project description:<h4>Importance</h4>Little is known regarding the association between level of blood pressure (BP) in young adulthood and cardiovascular disease (CVD) events by middle age.<h4>Objective</h4>To assess whether young adults who developed hypertension, defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline, before age 40 years have higher risk for CVD events compared with those who maintained normal BP.<h4>Design, setting, and participants</h4>Analyses were conducted in the prospective cohort Coronary Artery Risk Development in Young Adults (CARDIA) study, started in March 1985. CARDIA enrolled 5115 African American and white participants aged 18 to 30 years from 4 US field centers (Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California). Outcomes were available through August 2015.<h4>Exposures</h4>Using the highest BP measured from the first examination to the examination closest to, but not after, age 40 years, each participant was categorized as having normal BP (untreated systolic BP [SBP] <120 mm Hg and diastolic BP [DBP] <80 mm Hg; n = 2574); elevated BP (untreated SBP 120-129 mm Hg and DBP <80 mm Hg; n = 445); stage 1 hypertension (untreated SBP 130-139 mm Hg or DBP 80-89 mm Hg; n = 1194); or stage 2 hypertension (SBP ≥140 mm Hg, DBP ≥90 mm Hg, or taking antihypertensive medication; n = 638).<h4>Main outcomes and measures</h4>CVD events: fatal and nonfatal coronary heart disease (CHD), heart failure, stroke, transient ischemic attack, or intervention for peripheral artery disease (PAD).<h4>Results</h4>The final cohort included 4851 adults (mean age when follow-up for outcomes began, 35.7 years [SD, 3.6]; 2657 women [55%]; 2441 African American [50%]; 206 taking antihypertensive medication [4%]). Over a median follow-up of 18.8 years, 228 incident CVD events occurred (CHD, 109; stroke, 63; heart failure, 48; PAD, 8). CVD incidence rates for normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension were 1.37 (95% CI, 1.07-1.75), 2.74 (95% CI, 1.78-4.20), 3.15 (95% CI, 2.47-4.02), and 8.04 (95% CI, 6.45-10.03) per 1000 person-years, respectively. After multivariable adjustment, hazard ratios for CVD events for elevated BP, stage 1 hypertension, and stage 2 hypertension vs normal BP were 1.67 (95% CI, 1.01-2.77), 1.75 (95% CI, 1.22-2.53), and 3.49 (95% CI, 2.42-5.05), respectively.<h4>Conclusions and relevance</h4>Among young adults, those with elevated blood pressure, stage 1 hypertension, and stage 2 hypertension before age 40 years, as defined by the blood pressure classification in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, had significantly higher risk for subsequent cardiovascular disease events compared with those with normal blood pressure before age 40 years. The ACC/AHA blood pressure classification system may help identify young adults at higher risk for cardiovascular disease events.
Project description:BACKGROUND:The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline provides updated recommendations for antihypertensive medication initiation and intensification. OBJECTIVES:Determine the risk for cardiovascular disease (CVD) events among adults recommended and not recommended antihypertensive medication initiation or intensification by the 2017 ACC/AHA BP guideline. METHODS:The authors analyzed data for black and white REGARDS (REasons for Geographic And Racial Differences in Stroke) study participants (age ?45 years). Systolic BP (SBP) and diastolic BP (DBP) were measured twice at baseline (2003 to 2007) and averaged. Participants not taking (n = 14,039) and taking (n = 15,179) antihypertensive medication were categorized according to their recommendations for antihypertensive medication initiation and intensification by the 2017 ACC/AHA guideline. Overall, 4,094 CVD events (stroke, coronary heart disease, and heart failure) occurred by December 31, 2014. RESULTS:Among participants not taking antihypertensive medication, 34.4% were recommended pharmacological antihypertensive treatment initiation. The CVD event rate per 1,000 person-years among participants recommended antihypertensive medication initiation with SBP/DBP ?140/90 mm Hg was 22.7 (95% confidence interval [CI]: 20.3 to 25.0). Among participants with SBP/DBP 130 to 139/80 to 89 mm Hg, the CVD event rate was 20.5 (95% CI: 18.5 to 22.6) and 3.4 (95% CI: 2.4 to 4.4) for those recommended and not recommended antihypertensive medication initiation, respectively. Among participants taking antihypertensive medication, 62.8% were recommended treatment intensification. The CVD event rate per 1,000 person-years among participants recommended treatment intensification was 33.6 (95% CI: 31.5 to 35.6) and 22.4 (95% CI: 20.8 to 23.9) for those with SBP/DBP ?140/90 mm Hg and 130 to 139/80 to 89 mm Hg, respectively. CONCLUSIONS:Implementing the 2017 ACC/AHA guideline would direct antihypertensive medication initiation and intensification to adults with high CVD risk.
Project description:<h4>Background</h4>Several atherosclerotic cardiovascular disease (ASCVD) risk factors are associated with awake and nocturnal hypertension.<h4>Methods</h4>We assessed the association between a composite ASCVD risk score and awake or nocturnal hypertension using data from participants aged 40-79 years who completed ambulatory blood pressure monitoring at the Year 30 Coronary Artery Risk Development in Young Adults study exam in 2015-2016 (n = 716) and the baseline Jackson Heart Study exam in 2000-2004 (n = 770). Ten-year predicted ASCVD risk was calculated using the Pooled Cohort risk equations. Awake hypertension was defined as mean awake systolic blood pressure (SBP) ≥135 mm Hg or diastolic blood pressure (DBP) ≥85 mm Hg and nocturnal hypertension was defined as mean asleep SBP ≥120 mm Hg or DBP ≥70 mm Hg.<h4>Results</h4>Among participants with a 10-year predicted ASCVD risk <5%, 5% to <7.5%, 7.5% to <10%, and ≥10%, the prevalence of awake or nocturnal hypertension as a composite outcome was 29.5%, 47.8%, 62.2%, and 69.7%, respectively. After multivariable adjustment, higher ASCVD risk was associated with higher prevalence ratios for awake or nocturnal hypertension among participants with clinic-measured SBP/DBP <130/85 mm Hg but not ≥130/85 mm Hg. The C-statistic for discriminating between participants with vs. without awake or nocturnal hypertension was 0.012 (95% confidence interval 0.003, 0.016) higher when comparing a model with ASCVD risk and clinic-measured blood pressure (BP) together vs. clinic-measured BP without ASCVD risk.<h4>Conclusions</h4>Using 10-year predicted ASCVD risk in conjunction with clinic BP improves discrimination between individuals with and without awake or nocturnal hypertension.
Project description:Importance:Little is known regarding health outcomes associated with higher blood pressure (BP) levels measured outside the clinic among African American individuals. Objective:To examine whether daytime and nighttime BP levels measured outside the clinic among African American individuals are associated with cardiovascular disease (CVD) and all-cause mortality independent of BP levels measured inside the clinic. Design, Setting, and Participants:This prospective cohort study analyzed data from 1034 African American participants in the Jackson Heart Study who completed ambulatory BP monitoring at baseline (September 26, 2000, to March 31, 2004). Mean daytime and nighttime BPs were calculated based on measurements taken while participants were awake and asleep, respectively. Data were analyzed from July 1, 2017, to April 30, 2019. Main Outcomes and Measures:Cardiovascular disease events, including coronary heart disease and stroke, experienced through December 31, 2014, and all-cause mortality experienced through December 31, 2016, were adjudicated. The associations of daytime BP and nighttime BP, separately, with CVD events and all-cause mortality were determined using Cox proportional hazards regression models. Results:A total of 1034 participants (mean [SD] age, 58.9 [10.9] years; 337 [32.6%] male; and 583 [56.4%] taking antihypertensive medication) were included in the study. The mean daytime systolic BP (SBP)/diastolic BP (DBP) was 129.4/77.6 mm Hg, and the mean nighttime SBP/DBP was 121.3/68.4 mm Hg. During follow-up (median [interquartile range], 12.5 [11.1-13.6] years for CVD and 14.8 [13.7-15.6] years for all-cause mortality), 113 CVD events and 194 deaths occurred. After multivariable adjustment, including in-clinic SBP and DBP, the hazard ratios (HRs) for CVD events for each SD higher level were 1.53 (95% CI, 1.24-1.88) for daytime SBP (per 13.5 mm Hg), 1.48 (95% CI, 1.22-1.80) for nighttime SBP (per 15.5 mm Hg), 1.25 (95% CI, 1.02-1.51) for daytime DBP (per 9.3 mm Hg), and 1.30 (95% CI, 1.06-1.59) for nighttime DBP (per 9.5 mm Hg). Nighttime SBP was associated with all-cause mortality (HR per 1-SD higher level, 1.24; 95% CI, 1.06-1.45), but no association was present for daytime SBP (HR, 1.13; 95% CI, 0.97-1.33) and daytime (HR, 0.95; 95% CI, 0.81-1.10) and nighttime (HR, 1.06; 95% CI, 0.90-1.24) DBP. Conclusions and Relevance:Among African American individuals, higher daytime and nighttime SBPs were associated with an increased risk for CVD events and all-cause mortality independent of BP levels measured in the clinic. Measurement of daytime and nighttime BP using ambulatory monitoring during a 24-hour period may help identify African American individuals who have an increased cardiovascular disease risk.
Project description:Few studies have compared different blood pressure (BP) indexes for end-stage renal disease (ESRD) risk among individuals with chronic kidney disease.We examined the relationship between systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean arterial pressure (MAP) and ESRD risk among 2,772 participants with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) calculated using the Chronic Kidney Disease Epidemiology Collaboration equation in the REasons for the Geographic And Racial Differences in Stroke (REGARDS) study. BP was measured during a baseline study visit between January 2003 and October 2007 with ESRD incidence through August 2009 ascertained via linkage with the United States Renal Data System (n = 138 ESRD cases).The mean age was 72.1(standard deviation: 8.7) years. After multivariable adjustment for socio-demographic and clinical risk factors including antihypertensive medication use, the hazard ratio (HR) for ESRD associated with one standard deviation higher SBP (18 mm Hg) was 1.67, (95% confidence intervals (CI) 1.43-1.96), DBP (11 mm Hg) was 1.38, (95% CI 1.16-1.63), PP (15 mm Hg) was 1.50, (95% CI 1.27-1.78) and MAP (11 mm Hg) was 1.54, (95% CI 1.32-1.79). Higher levels of SBP remained associated with an increased HR for ESRD after additional adjustment for DBP (1.65, 95% CI: 1.35-2.01), PP (1.73, 95% CI: 1.32-2.26), and MAP (1.61, 95% CI: 1.16-2.23). After adjustment for SBP, the other BP indexes were not significantly associated with incident ESRD.These data suggest that of several blood pressure indexes including DBP, PP and MAP, SBP may have the strongest association with ESRD incidence among individuals with reduced eGFR.