J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. Hemodynamic Responses to Resistance Exercise in Patients with Coronary Artery Disease. Physical ischaemia induced by isometric exercise facilitated collateral development in the remote ischaemic myocardium of humans. Pulse pressure and risk of cardiovascular outcomes in patients with hypertension and coronary artery disease: an INternational VErapamil SR-trandolapril STudy (INVEST) analysis. Tracking Restoration of Park and Urban Street Settings in Coronary Artery Disease Patients Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous? Disorders of orthostatic blood pressure response are associated with cardiovascular disease and target organ damage in hypertensive patients. Blood Pressure and Cardiovascular Disease Risk in the Veterans Affairs Diabetes Trial
AIM In patients with coronary artery disease ( CAD ) , a J-curve relationship has been reported between blood pressure ( BP ) and future cardiovascular events . However , this is controversial . The purpose of the study was to determine the relationship between on-treatment BP and cardiovascular outcomes in patients with CAD . METHODS AND RESULTS We evaluated 10 001 patients with CAD and a low-density lipoprotein ( LDL ) cholesterol level < 130 mg/dL , r and omized to atorvastatin 80 vs. 10 mg , enrolled in the TNT trial . The post-baseline , time-dependent BPs [ systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) ] were categorized into 10 mmHg increments . The primary outcome was a composite of death from coronary disease , non-fatal myocardial infa rct ion ( MI ) , resuscitated cardiac arrest , and fatal or non-fatal stroke . Among the 10 001 patients , 982 ( 9.82 % ) experienced a primary outcome at 4.9 years ( median ) of follow-up . The relationship between SBP or DBP and primary outcome followed a J-curve with increased event rates above and below the reference BP range , both unadjusted and adjusted ( for baseline covariates , treatment effect , and LDL levels ) . A time-dependent , non-linear , multivariate Cox proportional hazard model identified a nadir of 146.3/81.4 mmHg where the event rate was lowest . A similar non-linear relationship with a higher risk of events at lower pressures was found for most of the secondary outcomes of all-cause mortality , cardiovascular mortality , non-fatal MI , or angina . However , for the outcome of stroke , lower was better for SBP . CONCLUSION In patients with CAD , a low BP ( < 110 - 120/<60 - 70 mmHg ) portends an increased risk of future cardiovascular events ( except stroke ) PURPOSE Investigate hemodynamic responses of resistance exercise ( RE ) with moderate load ( i.e. , international guidelines for RE of patients ) versus RE with high load in patients with coronary artery disease ( CAD ) . METHODS Medically stable male ( n = 11 ) and female patients ( n = 4 ) treated with PCI or percutaneous coronary intervention , or coronary artery bypass surgery a minimum of 6 months before this study , performed three sets of 15RM and 4RM RE in a r and omized order on separate days . Beat-to-beat systolic ( SBP ) , diastolic ( DBP ) blood pressure , heart rate ( HR ) , stroke volume ( SV ) , cardiac output ( CO ) , and systemic vascular resistance ( SVR ) were monitored at preexercise , and continuously during RE . RESULTS Compared with preexercise , SBP and DBP ( mean of three sets ) increased by 12 % to 13 % ( both ; P < 0.001 ) and 35 % to 40 % after 15RM RE ( both ; P < 0.001 ) . 15RM SBP and DBP were higher than 4RM SBP and DBP ( both ; P < 0.001 ) . The SBP of the fourth repetition of 15 RM RE was similar to the SBP of the fourth repetition of 4RM RE . Compared with preexercise , SV increased moderately after 4RM and 15 RM RE , respectively ( both , P < 0.001 ) . HR increased more after 15RM compared with 4RM RE ( P < 0.05 ) ; thus , higher CO after 15RM ( compared with 4RM RE ; P < 0.05 ) was mainly caused by higher HR . SVR decreased by 15 % ( P < 0.001 ) and 50 % ( P < 0.01 ) after 4RM and 15RM RE . CONCLUSIONS SBP and DBP increased significantly more during moderate load RE ; thus , the magnitude of the external load is not the prime determinant of the pressure response during RE . If management of blood pressure is of concern , high load/low rep RE is preferable to medium load/high rep RE The aim of the present study was to investigate the effects of isometric-h and grip-induced PIT ( physical ischaemia training ) on remote coronary recruitment and growth . A total of 74 CAD ( coronary artery disease ) patients were r and omly assigned to either the IHG ( isometric h and grip group ) or NEG ( non-exercise group ) . Patients in the IHG performed isometric h and grip exercises during 1 min of coronary balloon occlusion , whereas patients in the NEG remained sedentary . CFI ( collateral flow index ) , HR ( heart rate ) , SBP ( systolic blood pressure ) and DBP ( diastolic blood pressure ) were evaluated before and at the end of occlusion . In a second study , 21 CAD patients were r and omly divided into the IHT ( isometric h and grip training ) group or the NTG ( non-training group ) . Patients in the IHT group performed 3 months of IHT , whereas patients in the control group remained sedentary . SPECT ( single-photon emission computed tomography ) was used to evaluate myocardial perfusion , and VEGF ( vascular endothelial growth factor ) levels were determined using ELISA . In the IHG , CFI was significantly higher than in the control group ( P<0.01 ) . HR , SBP and DBP in the IHG were significantly higher than in the NEG ( P<0.01 ) at the end of occlusion . In the second study , myocardial perfusion ( P<0.05 ) and left ventricular ejection fraction ( P<0.01 ) were significantly improved in the IHT group . VEGF levels in the IHT group were significantly increased ( P<0.01 ) . Levels of VEGF were negatively correlated with the summed rest score of SPECT ( r=-0.60 , P<0.01 ) . In conclusion , isometric h and grip exercise-induced PIT may promote remote collateral recruitment and growth in CAD patients AIM The purpose of this study was to assess the relationship between  pulse pressure  ( PP ) and cardiovascular outcomes in a large , elderly , coronary artery disease ( CAD ) population with hypertension , and compare the predictive power of PP with other blood pressure measures . METHODS AND RESULTS In INternational VErapamil-tr and olapril STudy , 22,576 CAD patients with hypertension ( mean age 66 years ) were r and omized to verapamil-SR or atenolol-based strategies and followed for 2.7 years ( mean ) . Primary outcome ( PO ) was time to first occurrence of death ( all-cause ) , non-fatal myocardial infa rct ion ( MI ) , or non-fatal stroke . Mean follow-up PP was summarized by 5 mmHg subgroups for association with incidence of PO . Stepwise Cox proportional hazards models were used to estimate adjusted relative hazard ratios ( HR ) for the risk of PO with follow-up PP as a continuous variable , with linear and quadratic terms . Similar models were constructed for follow-up systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and mean arterial pressures ( MAP ) . A -2 log-likelihood statistic was used to assess the predictive power of PP compared with SBP , DBP , and MAP . For follow-up PP , the incidence and adjusted HR for the PO formed a J- or U-shaped curve . After adjusting for baseline covariates , both linear and quadratic terms for PP were significant ( P < 0.0001 for both ) , with a nadir of 54 mmHg ( bootstrapping 95 % CI 42 - 60 mmHg ) . Similar quadratic relationships were found between PP and all-cause mortality or MI ; the relationship between PP and stroke was linear . Pulse pressure was a predictor of PO even after including SBP ( P = 0.007 linear term ) or DBP ( P < 0.0001 for both linear and quadratic terms ) or MAP ( P < 0.01 for both liner and quadratic terms ) in the model . Using -2 log-likelihood differences , SBP ( -2 log-likelihood difference 77.1 vs. 7.3 for PP ) , DBP ( -2 log-likelihood difference 138.5 vs. 44.6 for PP ) , and MAP ( -2 log-likelihood difference 125.0 vs. 13.4 for PP ) were stronger predictors of PO than PP . CONCLUSION In CAD patients with hypertension , PP ( on anti-hypertensive treatment ) is a weaker predictor of cardiovascular outcomes than SBP , DBP , or MAP The physiological effects of natural and urban environments on the cardiovascular system of coronary artery disease ( CAD ) patients are not fully understood . This controlled field study examines the effects of restorative walking in a park vs. in an urban street environment on CAD patients ’ stress parameters and cardiac function . Methods : Twenty stable CAD patients were r and omly allocated to 7 days controlled walking in a city park or in an urban street environment group . The relationship between different environmental exposures and health effects was analyzed using Wilcoxon signed-rank test and exact Mann-Whitney U test . Results : The mean reduction in cortisol levels and negative effects after the walk on the first day was greater in the city park than in the urban street exposed group , while a reduction in negative effects in the urban group were greater after seven days . The reduction in diastolic blood pressure ( DBP ) in the park group was evident on the seventh day before the walk ( −4 mm Hg , p = 0.031 ) and 60 min after the walk ( −6.00 mm Hg , p = 0.002 ) . The cortisol slope was negatively associated with the DBP changes ( r = −0.514 , p < 0.05 ) . Conclusions : Physical activity in a green environment with noise and air pollution levels lower than in an urban environment has a greater positive effect on CAD patients ’ stress level and hemodynamic parameters . Mitigating green environmental influences may allow urban residents to maintain health and reduce disability Context Experts debate the consequences of excessive lowering of diastolic pressure in patients with hypertension and coronary artery disease . Contribution This report is a secondary analysis of data from a large trial of 2 antihypertensive drug regimens in patients with known coronary artery disease . The authors found a J-shaped relationship between diastolic blood pressure and all-cause death and myocardial infa rct ion , with the increased risk occurring at diastolic blood pressures below 70 to 80 mm Hg , that is , the lower the diastolic pressure , the higher the risk . Caution s The study examined associations between blood pressure and outcomes ; it could not prove that the antihypertensive therapy that lowered diastolic pressure too much caused the adverse outcomes . The Editors For 2 decades , the hypertension literature has been haunted by the phenomenon of a paradoxical increase in morbidity and mortality with an excessive decrease in blood pressure ( J-curve ) . Indeed , several reports have shown that low diastolic pressure is associated with an increased risk for coronary heart disease and related mortality in older adults and in patients taking antihypertensive medications ( 1 - 13 ) . After doing a review and meta- analysis of pertinent studies , Farnett and colleagues ( 14 ) concluded that although there was no consistent J-shaped relationship between stroke and systolic or diastolic pressure , there was a consistent J-shaped relationship for cardiac events and diastolic pressure . These authors stated that this dichotomy in the relationship between diastolic pressure and target organ disease may leave a clinician with the uncomfortable choice of whether to prevent stroke or renal disease at the expense of coronary heart disease . These findings were at variance with the generally accepted dogma formulated by the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) ( 15 ) , which stated that the relationship between pressure and risk was strong , continuous , independent , predictive and etiologically significant . Within the past decade , the phenomenon of a J-curve has been studied in several large trials of normotensive and hypertensive patients ( 16 - 30 ) . Not surprisingly , arguments regarding whether a J-curve could be clinical ly significant have become somewhat contentious . That is , some rely on evidence that on-treatment diastolic pressure below 70 mm Hg does not increase risk for cardiovascular disease and thus deny an impairment of vital organ perfusion within the usual values achievable by antihypertensive treatment . Others , however , consider the J-curve a more real possibility , particularly for the heart . In contrast to other organs , the heart is perfused mostly during diastole and thus could be more vulnerable to diastolic pressure reduction . If a J-curve did exist , it should be most evident in patients with limited coronary perfusion , in other words , in those with manifest coronary artery disease ( CAD ) . Optimal blood pressure in patients with hypertension and CAD remains controversial because few r and omized clinical trials have been done in this population ( 31 , 32 ) . The International Verapamil-Tr and olapril Study ( INVEST ) ( 33 ) , a r and omized trial , evaluated more than 22000 patients with CAD and hypertension . This patient profile , together with unprecedented levels of blood pressure control , provided a unique opportunity to critically investigate the hypothesis that the risk for CAD would increase with an excessive decrease in diastolic pressure . Methods Study Design and Intervention The INVEST design , methods , and principal results have been previously published ( 33 ) . The trial used an open design with blinded end point assessment . In brief , clinical ly stable patients with CAD and hypertension were r and omly assigned to a verapamil sustained-releasebased or atenolol-based strategy .  Patients with previous myocardial infa rct ion ( MI ) within 3 months of enrollment or class IV or V congestive heart failure were excluded .  Blood pressure goals were based on JNC VI ( systolic pressure < 140 mm Hg and diastolic pressure < 90 mm Hg or systolic pressure < 130 mm Hg and diastolic pressure < 85 mm Hg in patients with diabetes or renal impairment ) ( 15 ) . The addition of tr and olapril or hydrochlorothiazide was recommended when necessary to achieve blood pressure goals . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . Documented CAD was defined as any of the following : remote ( 3 months before enrollment ) confirmed MI , coronary angiography showing more than 50 % narrowing of at least 1 major coronary artery , diagnosis of classic angina pectoris , or concordant abnormalities on 2 different signals ( electrocardiography , echocardiography , or radionuclide scans ) from stress test findings concordant for ischemia ( for example , ST-segment depression or perfusion defects on radionuclide scanning or wall-motion abnormalities on echocardiography or radionuclide scanning ) . Patient Monitoring and Follow-up Protocol visits were scheduled every 6 weeks for the first 6 months and then biannually until 2 years after the last patient was enrolled . Patients were assessed for response to treatment , symptoms , treatment adherence , and adverse effects at each visit and at the end of the study as detailed elsewhere ( 33 ) . Patient follow-up was complete when we received a final assessment form through the online data system or a death report . The Internet-based electronic data collection method used in INVEST did not accept the entry until all required fields were complete . Blood pressure  was measured by using a st and ard mercury sphygmomanometer with an appropriately sized cuff applied to the upper nondominant arm at heart level . By auscultation at the brachial artery , systolic pressure was recorded at the first Korotkoff sound and diastolic pressure was recorded at the disappearance of the fifth Korotkoff sound . Blood pressure was measured twice , at least 2 minutes apart , and the measurements were averaged . Study Outcomes The primary outcome was the first occurrence of all-cause death , nonfatal MI , or nonfatal stroke by intention-to-treat analysis . The MI and stroke definitions are detailed elsewhere ( 34 ) . These 3 components individually were the main secondary outcomes . For this analysis , additional outcomes included fatal and nonfatal MI , fatal and nonfatal stroke , and average on-treatment blood pressure before outcome or censoring . Ascertainment and blinded adjudication of outcomes were described previously ( 32 ) . Follow-up data were available for 22008 ( 97.5 % ) patients . Statistical Analysis The main conclusions of INVEST were that the 2 treatment strategies were equivalent with respect to the primary outcome , main secondary outcomes , and on-treatment systolic and diastolic pressures . Thus , data for all enrolled patients were combined and included in these analyses following the intention-to-treat principle . A P value of 0.05 or less was considered statistically significant . Patients without a primary outcome event were censored at their latest follow-up visit . Average follow-up systolic and diastolic pressures were calculated for each patient by using all post-baseline results , up to the date of primary outcome or censoring . The baseline value was substituted for patients with no post-baseline data ( n= 1154 ) . In this exploratory analysis , the proportions of patients were pooled by 10 mm Hg strata of average follow-up systolic pressure , and the distribution of primary outcome event rate was evaluated to determine whether the relationship was linear . A similar presentation was prepared for diastolic pressure . Because the frequency distributions seemed consistent with a quadratic curve , a quadratic Cox proportional hazards model was formed for the time to primary outcome for each blood pressure variable , with factors for blood pressure and blood pressure squared . Similarly , the relationship between each 10 mm Hg stratum of average systolic pressure and diastolic pressure and all-cause death , fatal and nonfatal MI , and fatal and nonfatal stroke was evaluated . For the time to primary outcome , a second model was fitted , adjusting for the following baseline covariates : age ( 10-year increments ) , sex , race and ethnicity ( white , Asian , black , Hispanic , multiracial , or other ) , previous MI , heart failure ( classes I to III ) , body mass index in increments of 5 kg/m2 , U.S. residency , renal impairment , peripheral vascular disease , left ventricular hypertrophy , smoking history , coronary revascularization , dyslipidemia , stroke or transient ischemic attack , angina pectoris , arrhythmia , diabetes , cancer , aspirin use , and average systolic pressure or diastolic pressure and systolic pressure squared or diastolic pressure squared . To identify clinical ly relevant interactions between the J-shaped curve and baseline diastolic pressure , demographic characteristics , and comorbid conditions for the primary outcome , a 2-step procedure was used . First , baseline covariates were tested individually by adding the variable and 2 interaction terms ( variablediastolic pressure and variable[diastolic pressure squared ] ) to the Cox proportional hazards model . Variables included were age older than 70 years , sex , previous MI , heart failure ( classes I to III ) , previous stroke or transient ischemic attack , diabetes , cancer , renal impairment , hypercholesterolemia , peripheral vascular disease , smoking history , U.S. residency , body mass index greater than 29 kg/m2 ( mean baseline body mass index ) , and diastolic pressure greater than 86 mm Hg ( mean baseline diastolic pressure ) . The change in log likelihood was used to assess the significance of simultaneously adding the 2 interaction terms . The second step in identifying clinical ly relevant interactions between the J-shaped curve and baseline covariates was to plot the hazard ratios for the primary outcome versus diastolic pressure in the BACKGROUND The prevalence and clinical significance of orthostatic hypertension  ( OHT ) remain largely undetermined in hypertensive patients . This study investigated the association of OHT and  orthostatic hypotension ( OH )  with cardiovascular disease ( CVD ) and target organ damage ( TOD ) in hypertensive patients . METHODS A cross-sectional study was conducted in 4,711 hypertensives and 826 normotensives , aged 40 - 75 years . OHT was defined as an increase in systolic blood pressure ( SBP ) of > or = 20 mm Hg , and OH was defined as either a reduction in SBP of at least 20 mm Hg or a reduction in diastolic BP ( DBP ) of at least 10 mm Hg during the first 3 min after st and ing . RESULTS Hypertension was only independently associated with a risk of OHT . After controlling for age , sex , and other confounders , OH was associated with peripheral artery disease ( PAD ) ( odds ratio ( OR ) 1.49 , 95 % confidence interval ( CI ) 1.15 - 1.89 , P < 0.01 ) , left ventricular hypertrophy ( LVH ) ( OR 1.48 , 95 % CI 1.12 - 1.93 , P < 0.001 ) , coronary artery disease ( CAD ) ( OR 1.71 , 95 % CI 1.12 - 2.61 , P < 0.01 ) , and stroke ( OR 1.72 , 95 % CI 1.19 - 2.34 , P < 0.01 ) , but OHT was only associated with PAD ( OR 1.36 , 95 % CI 1.05 - 1.81 , P < 0.05 ) and stroke ( OR 1.76 , 95 % CI 1.27 - 2.26 , P < 0.01 ) . The adjusted OR for PAD , predicted by the quintiles of the orthostatic SBP changes , showed a J-shaped relationship in untreated hypertensive patients , as was also the case for LVH in hypertensive women . CONCLUSIONS OH is associated with CV risk ; the associations of OHT with TOD and stroke in hypertensive patients still need to be confirmed in prospect i ve studies OBJECTIVE Blood pressure ranges associated with cardiovascular disease ( CVD ) events in advanced type 2 diabetes are not clear . Our objective was to determine whether baseline and follow-up ( On- Study ) systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and SBP combined with DBP predict CVD events in the Veterans Affairs Diabetes Trial ( VADT ) . RESEARCH DESIGN AND METHODS Participants in the VADT ( n = 1,791 ) with hypertension received stepped treatment to maintain blood pressure below the target of 130/80 mmHg in st and ard and intensive glycemic treatment groups .  Blood pressure levels of all subjects at baseline and On- Study were analyzed to detect associations with CVD risk . The primary outcome was the time from r and omization to the first occurrence of myocardial infa rct ion , stroke , congestive heart failure , surgery for vascular disease , inoperable coronary disease , amputation for ischemic gangrene , or CVD death . RESULTS Separated SBP ≥140 mmHg had significant risk at baseline ( hazards ratio [ HR ] 1.508 , P < 0.001 ) and On- Study ( HR 1.469 , P = 0.002 ) . DBP < 70 mmHg increased CVD events at baseline ( HR 1.482 , P < 0.001 ) and On- Study ( HR 1.491 , P < 0.001 ) . Combined blood pressure categories indicated high risk for CVD events for SBP ≥140 with DBP < 70 mmHg at baseline ( HR 1.785 , P = 0.03 ) and On- Study ( HR 2.042 , P = 0.003 ) and nearly all SBP with DBP < 70 mmHg . CONCLUSIONS Increased risk of CVD events with SBP ≥140 mmHg emphasizes the urgency for treatment of systolic hypertension . Increased risk with DBP < 70 mmHg , even when combined with SBP in guideline -recommended target ranges , supports a new finding in patients with type 2 diabetes . The results emphasize that DBP < 70 mmHg in these patients was associated with elevated CVD risk and may best be avoided
These results suggest that reducing DBP to 80 mmHg or less would significantly reduce coronary revascularization and heart failure but at the expense of causing hypotension in CAD patients .
The target of diastolic blood pressure ( DBP ) remains controversial in patients with coronary artery disease ( CAD ) .