Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review Return of hypertension after withdrawal of prolonged antihypertensive therapy, effect of weight loss, sodium reduction, and baseline factors. Association between different lipid-lowering treatment strategies and blood pressure control in the Brisighella Heart Study. Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: post hoc analysis of the Australian National Blood Pressure Study Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study Blood pressure declines and less favorable outcomes in the NINDS tPA stroke study Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment. Long-Term Weight Loss and Changes in Blood Pressure: Results of the Trials of Hypertension Prevention, Phase II Sustained blood pressure control following discontinuation of a pharmacist intervention. Persistence of normotension after discontinuation of lifestyle intervention in the trial of TONE. Trial of Nonpharmacologic Interventions in the Elderly. Ten-year legacy effects of baseline blood pressure ‘treatment naivety’ in the Second Australian National Blood Pressure study Does withdrawal of antihypertensive medication increase the risk of cardiovascular events? Trial of Nonpharmacologic Interventions in the Elderly (TONE) Cooperative Research Group. Sustained Blood Pressure Control Following Discontinuation of a Pharmacist Intervention for Veterans. Antihypertensive therapy and the benefits of atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial: lipid-lowering arm extension Examination of lower targets for low-density lipoprotein cholesterol and blood pressure in diabetes--the Stop Atherosclerosis in Native Diabetics Study (SANDS). Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease.
Background Evidence on long term effectiveness of public health strategies for lowering blood pressure ( BP ) is scarce . In the Control of Blood Pressure and Risk Attenuation ( COBRA ) Trial , a 2 x 2 factorial , cluster r and omized controlled trial , the combined home health education ( HHE ) and trained general practitioner ( GP ) intervention delivered over 2 years was more effective than no intervention ( usual care ) in lowering systolic BP among adults with hypertension in urban Pakistan . However , it was not clear whether the effect would be sustained after the cessation of intervention . We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up . Methods A total of 1341 individuals 40 years or older with hypertension ( systolic BP 140 mm Hg or greater , diastolic BP 90 mm Hg or greater , or already receiving treatment ) were followed by trained research staff masked to r and omization status .  BP was measured thrice with a calibrated automated device ( Omron HEM-737 IntelliSense ) in the sitting position after 5 minutes of rest . BP measurements were repeated after two weeks . Generalized estimating equations ( GEE ) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up . The multivariable model was adjusted for clustering , age at baseline , sex , baseline systolic and diastolic BP , and presence of diabetes . Findings After 7 years of follow-up , systolic BP levels among those r and omised to combined HHE plus trained GP intervention were significantly lower ( 2.1 [ 4.1–0.1 ] mm Hg ) compared to those r and omised to usual care , ( P = 0.04 ) . Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol ( 2.7 [ 4.8 to 0.6 ] mg/dl . Conclusions The benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still evident at 7- year follow-up . These findings highlight the potential for scaling-up simple strategies for cardiovascular risk reduction in low- and middle- income countries . Trial Registration Clinical Trials.gov Background Many national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease ( CVD ) should no longer be based on BP level alone , but on absolute cardiovascular risk . While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP , clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain “ untreated ” . Objective We aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals ( 45 - 65 years ) with mildly elevated BP ( systolic BP 140 - 159 mmHg and /or diastolic BP 90 - 99 mmHg ) stratified by absolute risk for primary prevention of CVD , but particularly in the low-risk ( < 10 % five-year absolute risk ) group . Methods R and omized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process . First , r and omized trials of BP-lowering therapy will be identified by ( 1 ) retrieving the references of trials included in published systematic review s of BP-lowering therapy , ( 2 ) retrieving studies published by the Blood Pressure Lowering Treatment Trialists ’ Collaboration ( BPLTTC ) , and ( 3 ) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memor and um on BP management . Posttrial follow-up studies will then be identified by forward citation search ing the r and omized trials identified in step 1 through Web of Science . The search will include r and omized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase . Age is the major determinant of absolute cardiovascular risk , so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile . The primary outcome will be all-cause mortality . Secondary outcomes will include cardiovascular mortality , fatal stroke , fatal myocardial infa rct ion , and death due to heart failure . Results The search es for existing systematic review s and BPLTTC studies were piloted and modified . The study is expected to be completed before June 2018 . Conclusions The findings of this study will contribute to the body of knowledge concerning the beneficial , neutral , or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk . Trial Registration PROSPERO International Prospect i ve Register of Systematic Review s : CRD42017058414 ; https://www.crd.york.ac.uk/ PROSPERO /display_record.asp?ID = CRD42017058414 ( Archived by WebCite ® at http://www.webcitation.org/6t6sa8O2Q The effect of dietary modification on continued blood pressure control after discontinuation of antihypertensive therapy has been studied . Participants who had been treated for 5 years in the Hypertension Detection and Follow-up Program were enrolled and r and omly assigned to continue medication , discontinue medication with no dietary intervention , discontinue medication and reduce weight , discontinue medication and reduce sodium groups .  Relapse of hypertension was slow , even without dietary modification . Both weight loss and sodium restriction slowed relapse . The severity of the hypertension and the number of drugs required for hypertension control had a marked effect on the rate of relapse . Relapse was slowest in the participants who had attained the lowest blood pressure on therapy BACKGROUND Small studies have suggested that lipid-lowering strategies , and particularly statins , could influence blood pressure ( BP ) control . The aim of the present study was to evaluate the effect of different lipid-lowering strategies on BP control of subjects with hypercholesterolemia who were enrolled in the prospect i ve , population -based , longitudinal Brisighella Heart Study . METHODS A total of 1356 subjects with total cholesterol levels > or=239 mg/dL were r and omly treated for 5 years ( 1988 - 1993 ) with 1 of these lipid-lowering regimens : low-fat diet , cholestyramine , gemfibrozil , or simvastatin . Participants were divided at baseline into 4 quartiles according to systolic BP level and examined for the percent change in systolic and diastolic BP during the 5 years of treatment . RESULTS A significant decrease in BP was observed in the 2 upper quartiles of systolic BP ( > or=140 mm Hg ) and was greater in subjects treated with cholesterol-lowering drugs who also had a greater reduction in plasma levels of low-density lipoprotein cholesterol . The BP decrease was greater in patients treated with statin drugs and , among those treated with antihypertensive drugs , in subjects in the fourth quartile . CONCLUSION The use of lipid-lowering measures could significantly improve BP control in subjects with both hypercholesterolemia and hypertension . The reduction in BP seems to be enhanced in subjects treated with statins Objectives In many current guidelines , blood pressure (BP)-lowering drug treatment for primary prevention of cardiovascular disease ( CVD ) is based on absolute risk . However , in clinical practice , therapeutic decisions are often based on BP levels alone . We sought to investigate which approach was superior by conducting a post hoc analysis of the Australian National Blood Pressure ( ANBP ) cohort , a seminal study establishing the efficacy of BP lowering in ‘ mild hypertensive ’ persons . Design A post hoc subgroup analysis of the ANBP trial results by baseline absolute risk tertile . Setting and participants 3244 participants aged 35–69 years in a community-based r and omised placebo controlled trial of blood pressure-lowering medication . Interventions Chlorothiazide500 mg versus placebo . Primary outcome measures All-cause mortality and non-fatal events ( non-fatal CVD , congestive cardiac failure , renal failure , hypertensive retinopathy or encephalopathy ) . Results Treatment effects were assessed by HR , absolute risk reduction and number needed to treat . Participants had an average 5-year CVD risk in the intermediate range ( 10.5±6.5 ) with moderately elevated BP ( mean 159/103 mmHg ) and were middle aged ( 52±8 years ) . In a subgroup analysis , the relative effects ( HR ) and absolute effects ( absolute risk reduction and number needed to treat ) did not statistically differ across the three risk groups except for the absolute benefit in all-cause mortality ( p for heterogeneity=0.04 ) . With respect to absolute benefit , drug treatment significantly reduced the number of events in the high-risk group regarding any event with a number needed to treat of 18 ( 10 to 64 ) , death from any cause with 45 ( 25 to 196 ) and major CVD events with 23 ( 12 to 193 ) . Conclusion Our analysis confirms that the benefit of treatment was substantial only in the high-risk tertile , reaffirming the rationale of treating elevated blood pressure in the setting of all risk factors rather than in isolation BACKGROUND Lipid-lowering agents are known to reduce long-term mortality in patients with stable coronary disease or significant risk factors . However , the effect of lipid-lowering therapy on short-term mortality immediately after an acute coronary syndrome has not been determined . We did an observational study using data from two r and omised trials to investigate this issue . METHODS We used data from the GUSTO IIb and PURSUIT trials to compare all-cause mortality among patients with acute coronary syndromes who were discharged on lipid-lowering agents ( n=3653 ) with those who were not ( n=17,156 ) . A propensity analysis was done to adjust for presumed selection biases in the prescription of lipid-lowering agents . FINDINGS Lipid-lowering therapy was associated with a smaller proportion of deaths at 30 days ( 17 [ 0.5 % ] vs 179 [ 1.0 % ] , hazard ratio 0.44 [ 95 % CI 0.27 - 0.73 ] , p=0.001 ) and at 6 months ( 63 [ 1.7 % ] vs 605 [ 3.5 % ] , 0.48 [ 0.37 - 0.63 ] , p<0.0001 ) . After adjustment for the propensity to be prescribed lipid-lowering agents and other potential confounders , prescription of a lipid-lowering agent at discharge remained associated with a reduced risk of death at 6 months ( 0.67 [ 0.48 - 0.95 ] , p=0.023 ) . INTERPRETATION Prescription of a lipid-lowering drug at hospital discharge was independently associated with reduced short-term mortality among patients after an acute coronary syndrome BACKGROUND AND PURPOSE Hypertension is the most important modifiable risk factor for secondary stroke prevention but the immediate management of blood pressure after stroke is uncertain . We evaluated outcomes in the NINDS tPA stroke study in relation to blood pressure declines during the first 24 h after r and omization . METHODS Declines in blood pressure compared to baseline and preceding time points were analyzed in relationship to favorable outcomes ( by a global test ) , poor outcomes ( Rankin scale > 3 ) and death at 3 months . RESULTS 551 patients did not receive immediate pre-r and omization anti-hypertensive treatment and had available blood pressures . Multivariate analysis showed significantly and progressively reducing likelihoods of a favorable outcome with each 10 mmHg decline in systolic blood pressure ( SBP ) > 50 mmHg compared to any preceding measurement . Poor outcomes were significantly more likely in patients with > 50 mmHg SBP reduction ( or > 30 mmHg compared to any immediately preceding measurement ) . There was an increased risk of death with blood pressure declines > 60 mmHg . tPA treatment still produced favorable outcomes compared with placebo even with blood pressure declines . The median largest SBP reduction from baseline in patients treated with tPA was 35 mmHg compared to 30 mmHg in placebo-treated patients ( p<0.01 ) . CONCLUSIONS In this post hoc analysis , progressively reducing likelihoods of a favorable outcome were seen with increasing declines in SBP . Despite a greater likelihood of favorable outcomes , tPA treatment was associated with a greater reduction in blood pressure than placebo . R and omized trials of blood pressure management are needed BACKGROUND Local pulse pressure ( PP ) is an independent determinant of carotid artery wall thickness , stronger than mean blood pressure ( BP ) . The present study was design ed to assess whether a beta-adrenoceptor antagonist-based or an ACE inhibitor-based treatment was able to reduce carotid artery wall hypertrophy through a reduction in carotid PP rather than by lowering mean BP and whether the influence of local PP reduction could also be detected at the site of a muscular artery , the radial artery . METHODS AND RESULTS Ninety-eight essential hypertensive patients were r and omized to 9 months of double-blind treatment with either celiprolol or enalapril . Arterial parameters were determined with high-resolution echo-tracking systems . PP was measured locally with applanation tonometry and independently of mean BP . After 9 months of treatment , mean BP , carotid PP , and intimal-medial thickness ( IMT ) decreased significantly , with no difference between the 2 groups . The reduction in carotid PP but not in mean BP was a major independent determinant of the reduction in carotid IMT . Radial artery IMT and PP decreased significantly with both treatments . However , the reduction in radial artery IMT was not related to the changes in radial artery PP . CONCLUSIONS The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP . The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery Approximately one fourth of the U.S. adult population nearly 50 million peoplehas hypertension ( 1 , 2 ) . Taking a broader perspective , more than half of the adult population has higher than optimal blood pressure ( 1 ) , defined as systolic blood pressure greater than 120 mm Hg and diastolic blood pressure greater than 80 mm Hg ( 2 ) . These persons are at significantly increased risk for cardiovascular disease and stroke ( 3 ) . Although pharmacologic treatment for hypertension significantly reduces morbidity and mortality from cardiovascular diseases ( 4 , 5 ) , long-term pharmacologic therapy can have undesirable side effects and requires the expense of continuing medical supervision . Furthermore , pharmacologic therapy is not usually initiated when blood pressure is higher than optimal yet below diagnostic thresholds for hypertension . Thus , lifestyle interventions for primary prevention and initial treatment of high blood pressure remain a vital strategy for controlling this highly prevalent condition ( 2 ) . Weight loss has been shown to reduce blood pressure in overweight hypertensive patients ( 6 - 9 ) and in overweight persons with high-normal blood pressure ( 10 - 12 ) . Two review s of r and omized trials of weight reduction to reduce blood pressure examined the results of nine studies ( 13 , 14 ) . Most of these trials were small , only one had more than 500 participants ( 11 ) , and most had short-term follow-up ( 1 year or less ) . Only three studies had follow-up of 3 to 5 years ( 8 , 10 , 11 ) . Compared with controls ,  weight loss  averaged nearly 7 kg in the short-term trials and approximately 3 kg in the three longer-term trials . In almost all trials , systolic blood pressure and diastolic blood pressure were reduced in the intervention groups . Since these review s were published , the Trials of Hypertension Prevention ( TOHP ) Phase I reported mean weight reduction of 3.9 kg at 18 months in 564 overweight participants with high-normal blood pressure , result ing in significant decreases in systolic blood pressure and diastolic blood pressure compared with a usual care control group ( 12 , 15 ) . To investigate whether nonpharmacologic interventions can prevent hypertension over the long term , TOHP II was initiated . This was a r and omized , controlled trial examining the effects of  weight loss and dietary sodium reduction , alone and in combination , in reducing blood pressure in overweight adults with high-normal diastolic blood pressure ( 16 ) . This target population is at high risk for hypertension as they age . The primary outcome paper from this trial ( 17 ) provided only a brief overview of the effects of weight loss on blood pressure . Here , we provide more detailed analysis of weight loss and blood pressure in TOHP II . Of special interest are the long-term effects of weight loss on blood pressure , the magnitude of the doseresponse relationship at 36 months , the effect of patterns of weight loss on blood pressure , and the predictors of weight loss and blood pressure response . Methods Participants Participants in TOHP II were overweight adults with nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg . Other eligibility criteria included age 30 to 54 years and a body mass index of 26.1 to 37.4 kg/m2 for men and 24.4 to 37.4 kg/m2 for women , approximately 110 % to 165 % of ideal weight ( 18 ) . Principal exclusion criteria were current treatment with medications that might affect blood pressure , clinical or laboratory evidence of cardiovascular disease , diabetes mellitus , renal insufficiency ( serum creatinine concentration 150 mol/L [ 1.7 mg/dL ] for men and 132 mol/L [ 1.5 mg/dL ] for women ) , and current or planned pregnancy . Detailed descriptions of recruitment and participant characteristics have been published elsewhere ( 19 , 20 ) . The study was review ed and approved by the institutional review boards at all nine TOHP centers and the coordinating center , and all participants signed informed consent forms . Design Eligible participants were r and omly assigned with equal probability to one of four groups : weight loss only , sodium reduction only , combined weight loss and sodium reduction , or usual care ( controls ) . Measurements Age , sex , ethnicity , and years of education were obtained by question naire . Baseline blood pressure measurements were taken at three screening visits , each separated by 7 to 45 days . At each visit , three readings of systolic blood pressure and diastolic blood pressure were obtained and averaged . Certified staff obtained measurements in seated participants by using a Hawksley r and om-zero sphygmomanometer ( 21 ) . Body weight was measured to the nearest 0.2 kg ( 0.5 lb ) by using a calibrated balance-beam scale ; participants wore indoor clothing ( without shoes ) . Blood pressure and weight were measured every 6 months after r and omization to the end of follow-up at 36 , 42 , or 48 months , depending on r and omization date . Clinic staff who were blinded to study group assignment made these assessment s. Blood pressure measurements were obtained during a single visit at all follow-up points except for 18 and 36 months , when measurements were taken at a series of three visits approximately 1 week apart . Multiple measurements were taken at 18 and 36 months to provide a more precise assessment of average blood pressures at these primary outcome points . Dietary intake was assessed by 24-hour recall , and physical activity was assessed by question naire . Intervention Participants assigned to the weight loss intervention group sought to lose at least 4.5 kg ( 10 lb ) during the first 6 months of the intervention and to maintain their weight loss for the remainder of the trial . A brief description of the intervention methods is presented here ; a more detailed description has been published elsewhere ( 22 ) . The intervention started with an individual counseling session , followed by 14 weekly group meetings led by dietitians or health educators . After this 14-week intensive phase , participants attended six biweekly group meetings and then monthly group meetings . Beginning in the 18th month , participants were offered a variety of options to keep them involved in the intervention , including individual counseling sessions and special group sessions focused on selected weight loss topics . The intervention focused on self-directed behavior change ( behavioral self-management ) , nutrition education , information on physical activity , and social support for making and maintaining behavior changes . Specific behavior change techniques included self-monitoring ( food diaries and graphs of minutes of physical activity per day ) , setting explicit short-term goals and developing specific action plans to achieve those objectives , and developing alternative strategies for situations that trigger problem eating . The dietary intervention focused on reducing caloric intake by decreasing consumption of excess fat , sugar , and alcohol . Keeping daily food diaries was emphasized for monitoring intake and assessing progress . With experience , the participants determined the caloric intake that produced moderate weight loss for them . It was suggested that men not consume less than 1500 kcal/d and women not less than 1200 kcal/d . Weight loss of more than 0.9 kg ( 2 lb ) per week was discouraged . The physical activity goal was to gradually increase activity to 30 to 45 minutes per day , four to five days per week . Exercise intensity was moderate , approximately 40 % to 55 % of heart rate reserve , and consisted primarily of brisk walking . Statistical Analysis Baseline characteristics of the weight loss and usual care groups were compared overall and by sex by using t-tests for means and chi-square tests for proportions . Although weight and blood pressure data were collected every 6 months , special efforts were made to achieve high follow-up rates at 18 and 36 months ; at each of these two time points , nine blood pressure readings were collected over three visits and were averaged . For participants prescribed antihypertensive medication , follow-up blood pressure for all subsequent visits was taken to be the last study blood pressure before therapy was started . Participants receiving medications that affect blood pressure for reasons other than hypertension or who became pregnant were treated as missing at that visit . We used two- sample t-tests to compare changes in weight and blood pressure from baseline in the  weight loss intervention and usual care groups overall , by sex , by ethnicity , and by sex and ethnicity . The effects of the intervention in terms of changes in weight and blood pressure were examined overall and in subgroups defined by sex , ethnicity , and sex and ethnicity . Subgroup differences were tested by using terms for the interaction of treatment group with sex and with ethnicity in multiple linear regression models . Regression analyses were also used to analyze the doseresponse relationship between change in weight and change in blood pressure , overall and within sex and ethnicity subgroups . Differences in dose response were tested by using interaction terms in linear regression models . All regressions were adjusted for age and baseline weight . We also adjusted for baseline blood pressure in the blood pressure regression models . Change in blood pressure was also examined in relation to quintile of weight loss . Quintiles were computed by using the distribution of weight change in the weight loss intervention group . Additional multiple regression analyses were performed in which weight loss participants were categorized according to patterns of weight loss at 6 and 36 months . The PROC MIXED function of SAS software ( SAS Institute , Inc. , Cary , North Carolina ) was used to perform repeated- measures analyses that tested differences over time by pattern of weight loss . Cox proportional-hazards models were used for survival analyses , with onset of hypertension as the outcome . Results Baseline Findings The baseline characteristics of participants assigned to Team-based care can improve  hypertension control . The purpose of the present study was to evaluate blood pressure ( BP ) control 18 months following the discontinuation of a physician-pharmacist collaborative intervention . This was a retrospective analysis of patients who had previously participated in a prospect i ve , cluster r and omized , controlled clinical trial . Six community-based family medicine offices were r and omized to control or intervention groups . Research nurses measured BPs using an automated device during the prospect i ve trial . The research nurses then abstract ed data from medical records , including BPs , medications , changes in therapy , and laboratory values for 18 months following the discontinuation of the 6-month prospect i ve trial . The study included 228 patients in the control ( n = 146 ) or intervention ( n = 82 ) groups . The control group contained more patients with diabetes or chronic kidney disease ( P < .013 ) , were older ( P = .047 ) , and had more coexisting conditions ( P < .001 ) than the intervention group . Systolic BP 9 months following discontinuation of the physician-pharmacist intervention was 137.2 ± 18.2 mm Hg and 129.8 ± 13.3 mm Hg in the control and intervention groups , respectively ( P = .0015 ) . BP control was maintained in 61 ( 41.8 % ) control patients and 55 ( 67.1 % ) intervention patients ( P = .0003 ) . At 18 months post-intervention , systolic BP was 138.1 ± 20.4 mm Hg and 130.0 ± 16.0 mm Hg in the control and intervention groups , respectively ( P = .023 ) . BP control was maintained in 53 ( 36.3 % ) control patients and 55 ( 67.1 % ) intervention patients at 18 months post-intervention ( P < .0001 ) . A sensitivity analysis was conducted to address the uneven distribution of patients with diabetes or chronic kidney disease , and the differences between groups were still significant . BP control rates remained significantly higher following a physician-pharmacist intervention compared with usual care for 18 months after discontinuation of the intervention . This model has the potential value as a useful long-term strategy to benefit patients with hypertension BACKGROUND Weight loss and sodium reduction programs are effective in treating hypertension , but there is little information about the persistence of the benefit after discontinuation of the intervention . METHODS The Trial of Nonpharmacologic Interventions in the Elderly ( TONE ) was a four-center controlled clinical trial of weight loss , reduced sodium intake , or both in maintaining normotension after withdrawal of antihypertensive drug therapy in older men and women whose hypertension was controlled with a single antihypertensive medication . Information on maintenance of normotension without need for drug therapy was obtained on 222 of 223 participants at the Robert Wood Johnson Medical School clinical center on average of 48.4 months ( range 45 to 54 months ) after the end of TONE . RESULTS At the end of TONE follow-up , 43 % of participants in the combined intervention group were off medication compared with 25 % in the usual care group ( P = .011 ) . At 48 months after the end of TONE and discontinuation of contact of the participants with the clinical center , 23 % of the combined intervention group v 7 % in the usual care group were off medication ( P = .012 ) . CONCLUSIONS Some benefits of structured dietary intervention appears to persist long term in a significant number of patients after discontinuation of the intervention Objectives : Current blood pressure ( BP ) management guidelines recommend that treatment thresholds for BP be based on absolute cardiovascular disease ( CVD ) risk rather than on elevated BP levels alone . Clinicians are concerned that delayed pharmacotherapy in individuals with high BP , but low CVD risk , may increase long-term CVD events . To investigate this , we examined differences in CVD events within the Second Australian National BP study ( ANBP2 ) for those previously on pharmacotherapy and those who were not , as well as fatal events in the 6-year post-trial period . Methods : Population consisted of ANBP2 participants without a prior CVD event . Adjusted Cox-regression hazard models were used to assess the effects of prior BP pharmacotherapy use on cardiovascular endpoints within ANBP2 . An extended 6-year follow-up analysis for cardiovascular and all-cause mortality was also conducted . Results : We found a higher in-trial CVD and all-cause mortality rate and incidence of new-onset diabetes for those on previous treatment versus those who were treatment-naive . We investigated whether this was an effect of the in-trial protocol , but this did not explain the observed differences . No difference in CVD or all-cause mortality at 10 years was observed between ‘ treatment-naive ’ and ‘ previous treatment ’ groups . Conclusion : We found no long-term adverse mortality associated with treatment naivety of elevated BP in an elderly hypertensive cohort , but this finding is likely to be confounded as seen by the lower in-trial mortality in the ‘ treatment-naive ’ group . Legacy effects need to be explored in r and omized trials of middle-aged population s where the clinical concern lies The Fifth Report of the Joint National Committee on Detection , Evaluation , and Treatment of High Blood Pressure recommends that attempts to discontinue antihypertensive drug therapy be considered after blood pressure ( BP ) has been controlled for 1 year . However , discontinuation of drug therapy could unmask underlying conditions and precipitate clinical cardiovascular events . The Trial of Nonpharmacologic Interventions in the Elderly ( TONE ) was a clinical trial of the efficacy of weight loss and /or sodium reduction in controlling BP after withdrawal of drug therapy in patients with a BP < 145/85 mm Hg on 1 antihypertensive medication . Of 975 participants , 886 entered the drug withdrawal phase of the trial and 774 were successfully withdrawn from their medications . Thirty-three events ( stroke , transient ischemic attack , myocardial infa rct ion , arrhythmia , congestive heart failure , angina , other ) occurred between r and omization and the onset of drug withdrawal ( median time 3.6 months ) , 57 events occurred either during or after drug withdrawal ( 14.0 months ) , and 36 events occurred after resumption of antihypertensive therapy ( 15.9 months ) . Event rates per 100 person-years were 5.5 , 5.5 , and 6.8 for the 3 time periods ( p=0.84 ) in the nonoverweight group and 7.2 , 5.2 , and 5.6 ( p=0.08 ) in the overweight group . The study shows that antihypertensive medication can be safely withdrawn in older persons without clinical evidence of cardiovascular disease who do not have diastolic pressure > or = 150/90 mm Hg at withdrawal , providing that good BP control can be maintained with nonpharmacologic therapy Clinical pharmacists are utilized in Veterans Health Administration ( VHA ) facilities to assist with management of patients with chronic conditions including hypertension . The goal of this study was to examine blood pressure ( BP ) control after discontinuation of an intensive pharmacist-managed intervention .  The study was conducted at a single Midwest VHA medical center and two affiliated community-based outpatient clinics . Patients with uncontrolled BP received an intensive pharmacist intervention for the first 6 months . Patients were then stratified based on whether their BP was controlled or not and were r and omized to either continue the intervention for another 24 months ( 30 month total time period ) or the intervention was discontinued following one-time receipt of educational material  s. Mean systolic and diastolic BPs were reduced ( P<.001 ) in diabetic patients ( 8.0±14.4 mm Hg and 4.0±9.1 mm Hg , respectively ) and in nondiabetic patients ( 14.0±16.4 mm Hg and 5.0±10.0 mm Hg , respectively ) following the 6-month intervention , with 54 % of the total sample achieving BP control . BP control and the reduction in mean BP was maintained to a similar degree in both study groups at 12 , 18 , 24 , and 30 months . There were no significant differences in BP at any of the follow-up periods in patients who did and did not receive the continued pharmacist intervention . This study found that BP control was maintained for at least 24 months following discontinuation of an intensive pharmacist intervention . These findings were seen in both the group that had a continued pharmacist intervention and in the group that had a one-time educational session when the intervention was discontinued . This study suggests that once BP control is achieved following a pharmacist intervention , patients can be referred back to their primary care provider for continued follow-up Objective To determine the cardiovascular benefits of atorvastatin stratified by blood pressure-lowering regimen , 2.2 years after closure of the lipid-lowering arm ( LLA ) of the Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT-LLA ) . Methods In ASCOT-LLA , 10 305 hypertensive patients r and omized to amlodipine-based or atenolol-based therapy and with a total cholesterol 6.5 mmol/l or less were further r and omized to atorvastatin or placebo .  ASCOT-LLA was terminated after 3.3 years median follow-up . Cardiovascular outcomes in these patients were further evaluated 2.2 years later , at the end of the blood pressure-lowering arm ( BPLA ) . Results By the end of BPLA in both groups originally assigned statin or placebo , approximately 65 % were receiving a statin , and lipid levels had equalized . The benefits of atorvastatin observed in LLA were sustained throughout BPLA . At the end of BPLA , in those assigned amlodipine-based therapy , atorvastatin  reduced coronary heart disease deaths and nonfatal myocardial infa rct ion ( MI ) by 46 % [ hazard ratio 0.54 , confidence interval ( CI ) 0.40–0.72 , P < 0.0001 ] , stroke by 37 % [ hazard ratio 0.63 , CI 0.46–0.87 , P = 0.004 ] and total cardiovascular events and procedures by 27 % [ hazard ratio 0.73 , CI 0.63–0.86 , P < 0.0001 ] . In the atenolol-based group , atorvastatin  reduced coronary heart disease death and nonfatal MI by 25 % [ hazard ratio 0.75 , CI 0.57–0.97 , P = 0.03 ] , stroke by 10 % [ hazard ratio 0.90 , CI 0.69–1.18 , P = 0.43 ] and total cardiovascular events and procedures by 13 % [ hazard ratio 0.87 , CI 0.76–1.0 , P = 0.05 ] . P values for heterogeneity were low , but failed to achieve statistical significance ( 0.10 , 0.10 and 0.11 for chronic heart disease , stroke and total cardiovascular events , respectively ) . Conclusion Although not statistically significant , the benefits of atorvastatin appeared greater among those on amlodipine-based compared with atenolol-based therapy . These data provide supporting evidence that coassignment to atorvastatin may have generated differential effects on coronary and other cardiovascular outcomes by amlodipine-based and atenolol-based treatment in ASCOT-BPLA Diabetes incidence is increasing rapidly in the United States . Diabetes increases the risk for cardiovascular disease , the major cause of death in diabetic individuals . The conventional cardiovascular risk factors of hyperlipidemia and hypertension worsen diabetic vascular disease . Treatment targets for low-density lipoprotein cholesterol ( LDL-C ) and blood pressure in diabetic individuals are being debated . The S AND S is a r and omized , open-label , 3-year trial to examine the effects of aggressive LDL-C ( goal < 70 mg/dL ) and blood pressure ( BP ) ( goal < 115/75 mm Hg ) reduction versus the st and ard goals of < 100 mg/dL for LDL-C and < 130/85 mm Hg for BP .  Five hundred forty-nine American-Indian men and women > 40 years old with type 2 diabetes were r and omized to 1 of 2 groups . Lipids and BP are managed using Food and Drug Administration-approved medications in an algorithmic approach . The presence and progression of atherosclerosis are evaluated by carotid ultrasonography ; echocardiography assesses cardiac function . The primary end point is the composite outcome of change in carotid artery intimal medial thickness and fatal/nonfatal cardiovascular events . These outcomes are combined by using a ranked analysis for carotid thickness and assigning a " worst rank " for a cardiovascular event . Secondary end points include carotid plaque score , left ventricular geometry and function , serum C-reactive protein , and safety measures . Unique aspects of the study design and analysis plan involve the use of a composite outcome and changes during the trial of LDL-C treatment goals for participants with baseline or incident cardiovascular disease in the conventional group because of changes in the st and ard of care . Study results will further underst and ing of the effects of aggressive risk factor reduction on atherosclerosis burden and cardiac function in diabetic individuals in US population s and will help determine optimal LDL-C and BP treatment goals for diabetic patients Blood-pressure and cholesterol lowering in persons without cardiovascular disease Elevated blood pressure and elevated low-density lipoprotein ( LDL ) cholesterol increase the risk of cardiovascular disease . Lowering both should reduce the risk of cardiovascular events substantially . This proposition is examined in this r and omised trial in which patients without cardiovascular disease were r and omised to receive such treatments compared with placebos . The combination of rosuvastatin ( 10 mg per day ) , c and esartan ( 16 mg per day ) , and hydrochlorothiazide ( 12.5 mg per day ) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease .  Muscle weakness and dizziness were more common in the combined therapy group , but the rate of discontinuation was similar in the two groups
Results : BP and lipid levels tended to come together soon in the post-trial period .
Conclusion : Benefits of BPL and lipid lowering on all-cause and cardiovascular mortality were persistent , but attenuated , after discontinuation of r and omized treatment , indicating the importance of continuing therapy
Objective : Persistent long-term benefits after discontinuation of treatment have been suggested for blood pressure-lowering and lipid-lowering treatment .
We conducted a systematic review to assess the long-term effects of  blood pressure ( BP ) lowering ( BPL ) and lipid lowering on all-cause and cardiovascular mortality after discontinuation of r and omized treatment .