Is there a J-curve for hypertension and cardiovascular disease? How low can one go?

Transcription

1 Isser HS, et al 8. khras F, Dubrey S, Gazzard, et al. Emerging patterns of heart disease in HIV-infected homosexual subjects with and without opportunistic infections: prospective colour flow D o p p l e r e c h o c a r d i o g r a p h i c s t u d y. E u r H e a r t J. 99;():8 7. Review rticle 9. Vemuri DN, Robbins MJ, oals H. Does human immunodeficiency virus infection alter the course of infective endocarditis? J m Coll Cardiol. 99;:8. ddress for correspondence: Is there a J-curve for hypertension and cardiovascular disease? How low can one go? Dr. Isser HS ID: drhsisser@gmail.com Dr. Iyengar SS, DM Cardiology Consultant in Cardiology, Manipal Hospital, angalore bstract Guidelines on management of hypertension have laid down the blood pressure levels at which one should start treating hypertension and what should be the goals. There is an ongoing debate whether the relationship between P levels and cardiovascular events is a linear one or J-shaped. There are studies to support either side. While some argue that lower is better, some advocate caution that beyond a particular point of low P, there is an increased risk of cardiovascular events. J-curve probably exists for diastolic blood pressure in an elderly patient with hypertension and coronary artery disease. However, recent studies published this year seem to counter the concept of J-curve phenomenon. In the field of hypertension, we are going to look at the relationship between the blood pressure (P) levels and cardiovascular (CV) event rates. The J-curve phenomenon is a paradoxical increase in morbidity and mortality with an excessive decrease in P. P treatment guidelines have recommended P thresholds to commence treatment and also the P goals have been defined. However, there is a debate as to how low one can go to achieve optimal benefit from treatment. There is a concern that the therapeutic harm/benefit equation might tilt towards harm if there is aggressive P lowering in certain individuals, in certain situations and in certain organs. The debate of J-curve phenomena started in 979 and there is still no definitive answer. Factors supporting the J-curve phenomenon Hypertension Though there is no undisputable evidence for the existence of the J-curve phenomenon, it is supported by common sense (P value below which organ perfusion is compromised is bound to exist), physiological data, and observational studies. J-curve J-curve may have different pathophysiological mechanisms such as: Key Words CVD Introduction The term J-curve is commonly used in the world of economics, where the openness of the economy of the nation shows a J-shaped relationship with the political stability of the country and many believe that the J-curve is a new way to understand why nations rise and fall! It may be an epiphenomenon of a more severe underlying disease, low P being a marker of the illness, thereby increasing mortality Low P may be due to underlying impaired cardiac function Received: --; Revised: 8--; ccepted: -- Disclosures: This article has not received any funding and has no vested commercial interest cknowledgments: None 8 Nov Nov 87

2 This also has a clinical correlation where studies have shown that the CV event rates have a J-shaped relationship with diastolic P levels in patients with coronary artery disease (CD) who did not undergo coronary revascularization compared with those who were revascularized (Figure ). HT without LVH HT with LVH Flow (ml/min) Data from the ONTRGET trial showed that patients who showed P reduction to less than /8, more often exhibited J-shaped response during their visits (Figure ). In the INVEST study, the data on patients of diabetes compared the outcome in subjects in whom systolic P remained mmhg or more, with those where systolic P was reduced to between and 9 and less than mmhg. The all-cause mortality increased in patients with systolic P less than mmhg. The PRoFESS trial studied, patients with a history of stroke. The group with on-treatment P values between and 9 mmhg was taken as reference. The patients with systolic P more than mmhg showed decreasing risk of CV events up to the reference level of to 9. Systolic P levels falling below the reference levels again showed an increase in risk of CV events. 8 In TNT study on, patients with CD, low P ( / 7) portends an increased risk of future CV events (other than stroke) (Figure ) Coronary pertusion pressure (mmhg) Evidence against the J-curve phenomenon: With revascularization Without revascularization Hazard ratio In a study of prospective trials involving one million adults in the age group of to 89 years with no previous vascular disease, it was clearly shown that systolic blood pressure (SP) and diastolic blood pressure (DP) are strongly and directly related to vascular and overall mortality without evidence of 7 threshold down to /7 mmhg DP (mmhg) Figure : ) The effects of reducing coronary perfusion pressure by intravenous infusion of nitroprusside on coronary blood flow (measured in the great cardiac vein) in hypertensive patients with and 88 In the UKPDS trial, effect of P control was studied between patients with tight (P /8 mmhg) vs. less tight (/87 mmhg) control. These were 8 Type II diabetic patients with 9 years follow up. Patients with tight control of P showed significant risk reduction in stroke, heart failure, micro-vascular disease, any diabetic-related endpoint, and diabetes-related deaths. Nov Relative hazard, x 8 In the INVEST study,,7 patients of hypertension with CD were studied and the incidence of myocardial infarction (MI) clearly showed the J-curve phenomenon (almost U-shaped), whereas incidence of stroke did not show the J-curve. (high risk pts, mainly with CD) 9 On treatment SP [mmhg] 8 Unadjusted DP, mmhg TNT (CD patients) > Relative hazard, x The effects of reducing coronary perfusion pressure by intravenous infusion of nitroprusside on coronary blood flow (measured in the great cardiac vein) were studied in hypertensive patients with and without left ventricular hypertrophy (LVH). In hypertensive patients without LVH, there is no decrease in coronary blood flow till the coronary perfusion pressure of 7 mmhg. Whereas in patients with LVH, the coronary flow showed significant fall with coronary perfusion pressure at 9 mmhg (Figure ). djusted HR Clinical studies ONTRGET djusted HR Physiological data J-curve phenomenon may truly be existing without LVH; ) the CV event incidence at different achieved diastolic blood pressure (DP) levels in patients with coronary artery disease (CD) who did not undergo coronary revascularization compared with those who had the procedure. J-curve may be seen in patients with increased arterial stiffness, low P being a marker of high pulse pressure, and hence, the increase in mortality 8 fter adjustment for age, sex, ethnicity, smoking previous MI, heart failure, MI, renal failure, stroke/ti, peripheral vascular disease, aspirin use, average blood pressure, left ventricular hypertrophy, arrhythmia, residency in US On treatment DP [mmhg] DP, mmhg Figure : J-curve in the () ONTRGET and () TNT studies Figure : Unadjusted () and adjusted () relation between achieved (average in-treatment) DP and risk of primary outcome in hypertensive patients with coronary artery disease enrolled in the International Verapamil-Trandolapril Study Though there was % risk reduction in MI, it was not statistically significant. In the HOT study, 8,79 patients from countries in the age group of to 8 years were studied.9 Intensive lowering of P in hypertensive patients was associated with a low rate of CV events. The study showed the benefit of lowering DP down to 8. mmhg. The diabetes subgroup showed similar results. Wang et al., in an analysis of different trials, studied the effects of treatment on CV events in three different age groups, namely, 9, 79, and 8. SP and DP lowering clearly showed significant benefit in lowering the risk of all CV events, fatal and nonfatal stroke, and fatal and nonfatal MI. In the INVEST study, the unadjusted data showed the Jcurve phenomenon. ut after adjustment for age, gender, ethnicity, smoking, previous MI, heart failure, MI, renal failure, stroke/ti, peripheral vascular disease, aspirin use, arrhythmia, and LVH, the J-curve phenomenon disappeared (Figure ). Nov Limitations of the studies supporting the J-curve Following are limitations of the studies supporting Jcurve Lack of randomization: In the INVEST study, compared to patients with DP 8 9 mmhg, those with less than mmhg were years older, had previous MI, stroke, heart failure, diabetes, and cancer. There were a small number of patients with low or very low achieved P, i.e., a small number of patients in the ascending limb of J-curve. In the INVEST study, a DP of less than mmhg was seen in 7 patients of,7 patients, and in TNT study, a P of / or less was seen in 9 patients out of, patients. Most of the studies are observational data and post hoc analysis. Some of the results were unadjusted for confounding variables. 89

3 This also has a clinical correlation where studies have shown that the CV event rates have a J-shaped relationship with diastolic P levels in patients with coronary artery disease (CD) who did not undergo coronary revascularization compared with those who were revascularized (Figure ). HT without LVH HT with LVH Flow (ml/min) Data from the ONTRGET trial showed that patients who showed P reduction to less than /8, more often exhibited J-shaped response during their visits (Figure ). In the INVEST study, the data on patients of diabetes compared the outcome in subjects in whom systolic P remained mmhg or more, with those where systolic P was reduced to between and 9 and less than mmhg. The all-cause mortality increased in patients with systolic P less than mmhg. The PRoFESS trial studied, patients with a history of stroke. The group with on-treatment P values between and 9 mmhg was taken as reference. The patients with systolic P more than mmhg showed decreasing risk of CV events up to the reference level of to 9. Systolic P levels falling below the reference levels again showed an increase in risk of CV events. 8 In TNT study on, patients with CD, low P ( / 7) portends an increased risk of future CV events (other than stroke) (Figure ) Coronary pertusion pressure (mmhg) Evidence against the J-curve phenomenon: With revascularization Without revascularization Hazard ratio In a study of prospective trials involving one million adults in the age group of to 89 years with no previous vascular disease, it was clearly shown that systolic blood pressure (SP) and diastolic blood pressure (DP) are strongly and directly related to vascular and overall mortality without evidence of threshold down to /7 mmhg DP (mmhg) Figure : ) The effects of reducing coronary perfusion pressure by intravenous infusion of nitroprusside on coronary blood flow (measured in the great cardiac vein) in hypertensive patients with and 88 In the UKPDS trial, effect of P control was studied between patients with tight (P /8 mmhg) vs. less tight (/87 mmhg) control. These were 8 Type II diabetic patients with 9 years follow up. Patients with tight control of P showed significant risk reduction in stroke, heart failure, micro-vascular disease, any diabetic-related endpoint, and diabetes-related deaths. Nov Relative hazard, x 8 In the INVEST study,,7 patients of hypertension with CD were studied and the incidence of myocardial infarction (MI) clearly showed the J-curve phenomenon (almost U-shaped), whereas incidence of stroke did not show the J-curve. (high risk pts, mainly with CD) 9 On treatment SP [mmhg] 8 Unadjusted DP, mmhg TNT (CD patients) > Relative hazard, x The effects of reducing coronary perfusion pressure by intravenous infusion of nitroprusside on coronary blood flow (measured in the great cardiac vein) were studied in hypertensive patients with and without left ventricular hypertrophy (LVH). In hypertensive patients without LVH, there is no decrease in coronary blood flow till the coronary perfusion pressure of 7 mmhg. Whereas in patients with LVH, the coronary flow showed significant fall with coronary perfusion pressure at 9 mmhg (Figure ). djusted HR Clinical studies ONTRGET djusted HR Physiological data J-curve phenomenon may truly be existing without LVH; ) the CV event incidence at different achieved diastolic blood pressure (DP) levels in patients with coronary artery disease (CD) who did not undergo coronary revascularization compared with those who had the procedure. J-curve may be seen in patients with increased arterial stiffness, low P being a marker of high pulse pressure, and hence, the increase in mortality 8 fter adjustment for age, sex, ethnicity, smoking previous MI, heart failure, MI, renal failure, stroke/ti, peripheral vascular disease, aspirin use, average blood pressure, left ventricular hypertrophy, arrhythmia, residency in US On treatment DP [mmhg] DP, mmhg Figure : J-curve in the () ONTRGET and () TNT studies Figure : Unadjusted () and adjusted () relation between achieved (average in-treatment) DP and risk of primary outcome in hypertensive patients with coronary artery disease enrolled in the International Verapamil-Trandolapril Study Though there was % risk reduction in MI, it was not statistically significant. In the HOT study, 8,79 patients from countries in the age group of to 8 years were studied.9 Intensive lowering of P in hypertensive patients was associated with a low rate of CV events. The study showed the benefit of lowering DP down to 8. mmhg. The diabetes subgroup showed similar results. Wang et al., in an analysis of different trials, studied the effects of treatment on CV events in three different age groups, namely, 9, 79, and 8. SP and DP lowering clearly showed significant benefit in lowering the risk of all CV events, fatal and nonfatal stroke, and fatal and nonfatal MI. In the INVEST study, the unadjusted data showed the Jcurve phenomenon. ut after adjustment for age, gender, ethnicity, smoking, previous MI, heart failure, MI, renal failure, stroke/ti, peripheral vascular disease, aspirin use, arrhythmia, and LVH, the J-curve phenomenon disappeared (Figure ). Nov Limitations of the studies supporting the J-curve Following are limitations of the studies supporting Jcurve Lack of randomization: In the INVEST study, compared to patients with DP 8 9 mmhg, those with less than mmhg were years older, had previous MI, stroke, heart failure, diabetes, and cancer. There were a small number of patients with low or very low achieved P, i.e., a small number of patients in the ascending limb of J-curve. In the INVEST study, a DP of less than mmhg was seen in 7 patients of,7 patients, and in TNT study, a P of / or less was seen in 9 patients out of, patients. Most of the studies are observational data and post hoc analysis. Some of the results were unadjusted for confounding variables. 89

4 Organ heterogeneity ONTRGET study included high or very high CV risk hypertensive patients. The unadjusted risk of CV events and MI showed a J-curve phenomenon but not the risk of stroke. gain there is no evidence of the J-curve phenomenon for renal events when the P was lowered in type II diabetic patients after adjusting for age, gender, duration of diabetes, glycosylated hemoglobin, currently treated hypertension, ECG abnormalities, dyslipidemia, MI, smoking, alcohol use, and study drug. Cerebral autoregulation is probably more effective than the coronary autoregulation. Moreover, coronary circulation occurs mostly during diastole. New studies There are three new studies available and it is to be seen whether these contribute to clarity or confusion to the present debate. SPRINT: In this study, 9 patients were randomized into two treatment strategies of intensive P control (SP of mmhg or less) vs. standard P control (SP target of less than mmhg). Patients with diabetes, those with a history of stroke, and subjects less than years of age were excluded. The study was prematurely stopped because there was a statistically significant % reduction in the primary composite endpoint and % reduction in all-cause mortality with intensive P control. The benefit in primary endpoint was mostly driven by decrease in the risk of heart failure and mortality. There was no significant benefit in the risk of stroke, MI, or acute coronary syndrome (CS). However, this came at the cost of increased incidents of syncope, electrolyte abnormalities, and acute kidney injury. New CCORD Data (CCORDIN): The main CCORD trial after.9 years of follow up had shown a nonsignificant % reduction in composite CV events and a significant effect on stroke with intensive P control. Further, 97 patients were followed for an additional to months. There was a 9% nonsignificant reduction in primary CV events. There was a benefit of intensive P lowering in patients randomized to standard glycemic therapy. These results fit well with SPRINT study, and support SP lowering to 8 mmhg in patients with high CV risk or diabetes. Coronary circulation is unique with its dependency on diastole. Here, probably a J-curve phenomenon is likely to play a role, particularly in hypertensive patients who are old and not completely revascularized. Caution is to be exercised not to lower DP below mmhg. meta-analysis of 9 trials involving, patients showed that intensive P lowering ( P achieved /7 mmhg) significantly reduced major CV events, stroke, MI, albuminuria, and retinopathy progression. ut there was no benefit in heart failure, CV death, total mortality, or endstage renal disease compared with less intensive P lowering strategy(p achieved /8). The P levels are different and the benefits are different compared to SPRINT. The concern about J-curve phenomenon should not discourage clinicians from following guidelines in controlling hypertension and reach reaching targets recommended because, currently, P control in the hypertensive population is dismally low. What should we do? References In patients with elevated DP and CD with evidence of myocardial ischemia, the P should be lowered slowly, and caution is advised in inducing decreases in DP to < mmhg in any patient with diabetes or who is more than years of age.. Polese, De Cesare N, Montorsi P, et al. Upward shift of the lower range of coronary flow autoregulation in hypertensive patients with hypertrophy of the left ventricle. Circulation. 99;8:8.. Messerli FH, Mancia G, Conti CR, et al. Dogma disputed: Can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? nn Intern Med. ;: Mancia G, Schumacher H, Redon J, et al. lood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the Ongoing Telmisartan lone and in Combination With Ramipril Global Endpoint Trial (ONTRGET). Circulation. ;:77.. Cooper-DeHoff RM, Gong Y, Handberg EM, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JM. ;: 8.. Ovbiagele, Diener HC, Yusuf S, et al. Level of systolic blood pressure within the normal range and risk of recurrent stroke. JM. ;:7.. angalore S, Messerli FH, Wun CC, et al. J-curve revisited: n analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. Eur Heart J. ;: Lewington S, Clarke R, Qizilbash N, et al. ge-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in prospective studies. Lancet. ;:9. 8. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type diabetes: UKPDS 8. r Med J. In older hypertensive individuals with wide pulse pressures, lowering SP may cause low DP values (less than mmhg). This should alert the clinicians to assess carefully any untoward signs or symptoms, especially those resulting from myocardial ischemia (Class IIa, C). The P targets recommended for patients with CD are as follows: General CD prevention: </9 mmhg High CD risk: </8 mmhg Stable angina: </8 mmhg CS: </8 mmhg LV dysfunction: </8 mmhg In patients with stroke/ti, it is reasonable achieve a SP of less than and DP of less than 9 (Class IIa, ). 998;7:7. 9. Hansson L, Zanchetti, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 998;:7.. Wang JG, Staessen J, Franklin SS, et al. Systolic and diastolic blood pressure lowering as determinants of cardiovascular outcome. Hypertension. ;:97.. Mancia G, Schumacher H, Redon J, et al. lood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the Ongoing Telmisartan lone and in C o m b i n a t i o n Wi t h R a m i p r i l G l o b a l E n d p o i n t Tr i a l (ONTRGET). Circulation. ;:77.. de Galan E, Pekovic V, Ninomiya T, et al. Lowering blood pressure reduces renal events in type diabetes. J m Soc Nephrol. 9;: SPRINT Research Group, Wright JT Jr, Williamson JD, et al. randomized trial of intensive versus standard blood-pressure control. N Engl J Med. ;7():.. Cushman WC, Evans GW, Cutler J. Long-term cardiovascular effects of.9 years of intensive blood pressure control in type diabetes mellitus: The action to control cardiovascular risk in diabetes follow-on blood-pressure study. merican Heart ssociation Scientific Sessions; November, ; Orlando, FL. Xinfang Xie, Emily tkins, Jicheng LV. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Nov [Epub ahead of print]. doi: Rosendorff C, Lackland DT, llison M, et al. Treatment of hypertension in patients with coronary artery disease: scientific statement from the merican Heart ssociation, merican College of Cardiology, and merican Society of Hypertension. J m Coll Cardiol ;:. 7. Moser M, Wright JT, Victor RG, et al. How to treat hypertension in patients with coronary heart disease. J Clin Hypertens (Greenwich). 8:():9 7. ddress for correspondence: Dr. S S Iyengar ID: ssiyengar9@gmail.com In patients with a recent lacunar stroke, it is reasonable to target a SP of less than mmhg.7 Summary If one ventures to summarize the available data, the following points emerge. J-curve phenomenon may be an epiphenomenon ( reverse causality as in comorbid conditions, poor LV function, or arterial stiffness states) or in certain situations, a reality. Nov Nov 8

5 Organ heterogeneity ONTRGET study included high or very high CV risk hypertensive patients. The unadjusted risk of CV events and MI showed a J-curve phenomenon but not the risk of stroke. gain there is no evidence of the J-curve phenomenon for renal events when the P was lowered in type II diabetic patients after adjusting for age, gender, duration of diabetes, glycosylated hemoglobin, currently treated hypertension, ECG abnormalities, dyslipidemia, MI, smoking, alcohol use, and study drug. Cerebral autoregulation is probably more effective than the coronary autoregulation. Moreover, coronary circulation occurs mostly during diastole. New studies There are three new studies available and it is to be seen whether these contribute to clarity or confusion to the present debate. SPRINT: In this study, 9 patients were randomized into two treatment strategies of intensive P control (SP of mmhg or less) vs. standard P control (SP target of less than mmhg). Patients with diabetes, those with a history of stroke, and subjects less than years of age were excluded. The study was prematurely stopped because there was a statistically significant % reduction in the primary composite endpoint and % reduction in all-cause mortality with intensive P control. The benefit in primary endpoint was mostly driven by decrease in the risk of heart failure and mortality. There was no significant benefit in the risk of stroke, MI, or acute coronary syndrome (CS). However, this came at the cost of increased incidents of syncope, electrolyte abnormalities, and acute kidney injury. New CCORD Data (CCORDIN): The main CCORD trial after.9 years of follow up had shown a nonsignificant % reduction in composite CV events and a significant effect on stroke with intensive P control. Further, 97 patients were followed for an additional to months. There was a 9% nonsignificant reduction in primary CV events. There was a benefit of intensive P lowering in patients randomized to standard glycemic therapy. These results fit well with SPRINT study, and support SP lowering to 8 mmhg in patients with high CV risk or diabetes. Coronary circulation is unique with its dependency on diastole. Here, probably a J-curve phenomenon is likely to play a role, particularly in hypertensive patients who are old and not completely revascularized. Caution is to be exercised not to lower DP below mmhg. meta-analysis of 9 trials involving, patients showed that intensive P lowering ( P achieved /7 mmhg) significantly reduced major CV events, stroke, MI, albuminuria, and retinopathy progression. ut there was no benefit in heart failure, CV death, total mortality, or endstage renal disease compared with less intensive P lowering strategy(p achieved /8). The P levels are different and the benefits are different compared to SPRINT. The concern about J-curve phenomenon should not discourage clinicians from following guidelines in controlling hypertension and reach reaching targets recommended because, currently, P control in the hypertensive population is dismally low. What should we do? References In patients with elevated DP and CD with evidence of myocardial ischemia, the P should be lowered slowly, and caution is advised in inducing decreases in DP to < mmhg in any patient with diabetes or who is more than years of age.. Polese, De Cesare N, Montorsi P, et al. Upward shift of the lower range of coronary flow autoregulation in hypertensive patients with hypertrophy of the left ventricle. Circulation. 99;8:8.. Messerli FH, Mancia G, Conti CR, et al. Dogma disputed: Can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? nn Intern Med. ;: Mancia G, Schumacher H, Redon J, et al. lood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the Ongoing Telmisartan lone and in Combination With Ramipril Global Endpoint Trial (ONTRGET). Circulation. ;:77.. Cooper-DeHoff RM, Gong Y, Handberg EM, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JM. ;: 8.. Ovbiagele, Diener HC, Yusuf S, et al. Level of systolic blood pressure within the normal range and risk of recurrent stroke. JM. ;:7.. angalore S, Messerli FH, Wun CC, et al. J-curve revisited: n analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. Eur Heart J. ;: Lewington S, Clarke R, Qizilbash N, et al. ge-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in prospective studies. Lancet. ;:9. 8. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type diabetes: UKPDS 8. r Med J. In older hypertensive individuals with wide pulse pressures, lowering SP may cause low DP values (less than mmhg). This should alert the clinicians to assess carefully any untoward signs or symptoms, especially those resulting from myocardial ischemia (Class IIa, C). The P targets recommended for patients with CD are as follows: General CD prevention: </9 mmhg High CD risk: </8 mmhg Stable angina: </8 mmhg CS: </8 mmhg LV dysfunction: </8 mmhg In patients with stroke/ti, it is reasonable achieve a SP of less than and DP of less than 9 (Class IIa, ). 998;7:7. 9. Hansson L, Zanchetti, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 998;:7.. Wang JG, Staessen J, Franklin SS, et al. Systolic and diastolic blood pressure lowering as determinants of cardiovascular outcome. Hypertension. ;:97.. Mancia G, Schumacher H, Redon J, et al. lood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the Ongoing Telmisartan lone and in C o m b i n a t i o n Wi t h R a m i p r i l G l o b a l E n d p o i n t Tr i a l (ONTRGET). Circulation. ;:77.. de Galan E, Pekovic V, Ninomiya T, et al. Lowering blood pressure reduces renal events in type diabetes. J m Soc Nephrol. 9;: SPRINT Research Group, Wright JT Jr, Williamson JD, et al. randomized trial of intensive versus standard blood-pressure control. N Engl J Med. ;7():.. Cushman WC, Evans GW, Cutler J. Long-term cardiovascular effects of.9 years of intensive blood pressure control in type diabetes mellitus: The action to control cardiovascular risk in diabetes follow-on blood-pressure study. merican Heart ssociation Scientific Sessions; November, ; Orlando, FL. Xinfang Xie, Emily tkins, Jicheng LV. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Nov [Epub ahead of print]. doi: Rosendorff C, Lackland DT, llison M, et al. Treatment of hypertension in patients with coronary artery disease: scientific statement from the merican Heart ssociation, merican College of Cardiology, and merican Society of Hypertension. J m Coll Cardiol ;:. 7. Moser M, Wright JT, Victor RG, et al. How to treat hypertension in patients with coronary heart disease. J Clin Hypertens (Greenwich). 8:():9 7. ddress for correspondence: Dr. S S Iyengar ID: ssiyengar9@gmail.com In patients with a recent lacunar stroke, it is reasonable 7 to target a SP of less than mmhg. Summary If one ventures to summarize the available data, the following points emerge. J-curve phenomenon may be an epiphenomenon ( reverse causality as in comorbid conditions, poor LV function, or arterial stiffness states) or in certain situations, a reality. Nov Nov 8