Middle-Aged and Older Patients With Left Ventricular Hypertrophy: Higher Mortality With Drug Treated Systolic Blood Pressure Below 130 mm Hg.

BACKGROUND: Approximately 40% of people with hypertension have left ventricular hypertrophy (LVH) detected by ECG or echocardiography. Because patients with LVH have poor myocardial microcirculation, they may be too sensitive to lowering systolic blood pressure (SBP) too much due to a lack of myocardial perfusion pressure. We aimed to investigate whether the average achieved SBP <130 mm Hg may cause harm in patients with LVH in the Valsartan Antihypertensive Long-Term Use Evaluation trial (VALUE). METHODS: Of the 15 245 VALUE participants, we identified 13 803 patients without cardiovascular events during the first 6 months after randomization. Of these, 2458 patients had electrocardiographic LVH (ECG-LVH). Cox analyses adjusted for age, gender, and baseline variables compared cardiac and all-cause mortality and other prespecified end points for patients who achieved average SBP 130 to 139 mm Hg (No-LVH group n=4863; ECG-LVH group n=929) and <130 mm Hg (No-LVH group n=2107; ECG-LVH group n=305). Reference groups were patients who achieved average SBP ≥140 mm Hg following the first excluded 6 months (No-LVH group n=4375; ECG-LVH group n=1224). RESULTS: The No-LVH group achieving average SBP <130 mm Hg had a significantly lower incidence of several cardiovascular end points. The ECG-LVH group achieving average SBP <130 mm Hg had higher cardiac mortality (hazard ratio, 1.98 [95% CIs, 1.06-3.70]; P=0.032) and all-cause mortality (hazard ratio, 1.74 [95% CIs, 1.17-2.60]; P=0.007), and SBP <130 mm Hg was not associated with a reduction in any end point. CONCLUSIONS: Our findings may be seen as a signal that caution is warranted when treating middle-aged and older patients with electrocardiographic or echocardiographic LVH to SBP <130 mm Hg.

Novel insights into stroke risk beyond resting and maximal bicycle exercise systolic blood pressure.

OBJECTIVE: Previous research has shown an association between moderate workload exercise blood pressure (BP) and coronary disease, whereas maximal exercise BP is associated with stroke. We aimed to investigate the association between the increase in BP during maximal exercise and the long-term risk of stroke in healthy, middle-aged men. METHODS: Two thousand and fourteen men were included in the Oslo Ischemia Study in the 1970s. In the present study, we examined baseline data of the 1392 participants who remained healthy and performed bicycle exercise tests both at baseline and 7 years later. Cox proportional hazard was used to assess the risk of stroke in participants divided into quartiles based on the difference between resting and maximal workload SBP (ΔSBP) at baseline, adjusting for resting BP, age, smoking, serum cholesterol and physical fitness. Follow-up was until the first ischemic or hemorrhagic stroke through 35 years. RESULTS: There were 195 incident strokes; 174 (89%) were ischemic. In univariate analyses, there were significant positive correlations between age, resting SBP, resting DBP and SBP at moderate and maximal workload, and risk of stroke. In the multivariate analysis, there was a 2.6-fold (P < 0.0001) increase in risk of stroke in ΔSBP quartile 4 (ΔSBP > 99 mmHg) compared with ΔSBP quartile 2 (ΔSBP 73-85 mmHg), which had the lowest risk of stroke. ΔSBP quartile 1 had a 1.7-fold (P = 0.02) increased risk compared with quartile 2, suggesting a J-shaped association to stroke risk. CONCLUSION: Stroke risk increased with increasing difference between resting and maximal exercise SBP, independent of BP at rest, suggesting that an exaggerated BP response to physical exercise may be an independent predictor of stroke.

Exercise Systolic Blood Pressure at Moderate Workload Is Linearly Associated With Coronary Disease Risk in Healthy Men.

There is no consensus on the definition of an exaggerated increase in systolic blood pressure (SBP) during exercise. The aim was to explore a potential threshold for exercise SBP associated with increased risk of coronary heart disease in healthy men using repeated exercise testing. Two thousand fourteen healthy white male employees were recruited into the Oslo Ischemia Study during early 1970s. At follow-up 7 years later, 1392 men were still considered healthy. A bicycle exercise test at 100 W workload was performed at both visits. Cox regression analyses were performed with increasing cutoff levels of peak exercise SBP at 100 W workload (SBP100W) from 160 mm Hg to 200 mm Hg, adjusted for cardiovascular risk factors and physical fitness. Participants with SBP100W below cutoff level at both baseline and first follow-up were compared with participants with SBP100W equal to or above cutoff level at both visits. Compared with participants with SBP100W below all cutoff levels between 165 and 195 mm Hg, coronary heart disease risk was increased among participants with SBP100W equal to or above cutoff at all levels. There was no evidence of a distinct threshold level for coronary heart disease risk, and the relation between SBP100W and coronary heart disease appears linear. When investigating exercise SBP at moderate workload measured at 2 exercise tests in healthy middle-aged white men, there is increasing risk of coronary heart disease with increasing exercise SBP independent of SBP at rest. The association is linear from the low range of exercise SBP, and there is no sign of a distinct threshold level for increased coronary disease risk.

SBP above 180 mmHg at moderate exercise workload increases coronary heart disease risk in healthy men during 28-year follow-up.

OBJECTIVE: We investigated the association between exercise SBP at a moderate workload and long-term risk of coronary heart disease (CHD) in men who were healthy when assessed by two bicycle exercise tests 7 years apart. METHODS: During 1972-1975, apparently healthy men (n = 1999) were initially enrolled following thorough medical examination and ECG-monitored bicycle exercise test. Participants (n = 1392) who were healthy also at a second exercise test 7 years later were included in the present study. They were divided into quartiles, Q1-Q4, according to the highest SBP during the initial 6 min of the exercise test on a moderate workload of 100 W (SBP100W) at 7 years and followed for up to 28 years. Adjusted Cox regression was used to estimate CHD risk defined as first occurrence of angina pectoris, nonfatal myocardial infarction or CHD mortality. RESULTS: During follow-up, 452 of the 1392 men suffered incident CHD, and unadjusted, there was increased risk of CHD with increasing SBP100 W, with significant differences between Q1-Q4. In the multivariate analysis adjusting for classical coronary risk factors, including SBP at rest, there was increased risk of CHD in Q3 (SBP100 W above 180 mmHg) and Q4 (SBP100 W above 200 mmHg) compared with Q1 (≤160 mmHg, lowest SBP100 W), hazard ratios 1.42 (CI 1.07-1.90) and 1.93 (CI 1.38-2.70), respectively. CONCLUSION: Healthy middle-aged men had increased long-term risk of CHD with exercise SBP above 180 mmHg at moderate workload. The prognostic impact of SBP above 180 mmHg at exercise is independent of classical coronary risk factors and blood pressure at rest.

Physical fitness is a modifiable predictor of early cardiovascular death: A 35-year follow-up study of 2014 healthy middle-aged men.

Background Physical fitness has been shown to predict cardiovascular death during long-term follow-up. In the present study we aimed to investigate how physical fitness and other cardiovascular risk factors at middle-age influenced the risk of cardiovascular death during the early (0-11 years), intermediate (12-23 years) and late (24-35 years) parts of a 35-year observation period. Methods and results Age-adjusted physical fitness was calculated in 2014 apparently healthy, middle-aged men after maximal bicycle electrocardiogram-tests in 1972-1975 (Survey 1) and 1979-1982 (Survey 2). The men were assessed through 35 years after Survey 1, and 28 years after Survey 2 by Cox proportional hazards models. Low Survey 1 physical fitness was independently associated with increased risks of early and intermediate, but not late, cardiovascular death. Survey 1 to Survey 2 change in physical fitness, age, smoking status, systolic blood pressure and cholesterol impacted cardiovascular death risks in all periods. Family history of coronary heart disease impacted early and intermediate, but not late, cardiovascular death. Conclusions Most classical cardiovascular risk factors were strong predictors of early, intermediate and late cardiovascular death. Physical fitness measured at median age 50 years was independently associated with risk of early cardiovascular death, but the association weakened as time progressed. Change in physical fitness during middle-age impacted cardiovascular death risk in a full lifetime perspective. Thus, our data suggest that physical fitness is a modifiable cardiovascular risk factor with limited duration in contrast to the sustained impact of smoking, blood pressure and cholesterol on cardiovascular mortality.

Which Target Blood Pressure in Year 2018? Evidence from Recent Clinical Trials.

The Systolic Blood Pressure Intervention Trial (SPRINT) suggested a favourable effect of lowering blood pressure to < 120/80 mmHg in high-risk hypertensive patients; however, new American guidelines in 2017 have not followed SPRINT but lowered its recommended treatment target to < 130/80 mmHg. We aimed to review the latest research from large randomised controlled trials and observational analyses in order to investigate the evidence for new treatment targets. We assessed recent data from the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD) study, the International Verapamil-Trandolapril Study (INVEST), the Telmisartan, Ramipril or Both in Patients at High Risk for Vascular Events trial (ONTARGET)/the Telmisartan Randomised AssessmenNt Study in aCE iNtolerant participants with cardiovascular Disease (TRANSCEND) study and The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. These studies confirm a positive effect on cardiovascular protection with blood pressure lowering treatment to between 120-140 mmHg in patients with and without diabetes, but no additional effect of lowering blood pressure to < 120 mmHg; possibly too aggressive treatment may increase both cardiovascular morbidity and mortality. Thus, a target blood pressure < 130/80 mmHg appears appropriate in most high-risk hypertensive patients. Additionally, early and sustained BP control below this target is required for optimal cardiovascular protection.

Exercise systolic blood pressure at moderate workload predicts cardiovascular disease and mortality through 35 years of follow-up in healthy, middle-aged men.

OBJECTIVE: There is an association between exercise systolic blood pressure (SBP) and cardiovascular disease and mortality. The aim of this study was to investigate this association, with 35 years of follow-up. METHODS: Through 1972-75, 2014 healthy, middle-aged men underwent thorough medical examination and a bicycle exercise test. 1999 participants completed six minutes at 100 W. SBP was measured manually, both before the test and every two minutes during the test. Highest SBP measured during the first six minutes (SBP100W) was used in further analyses. RESULTS: Participants were divided into quartiles (Q) based on their SBP100W; Q1: 100-160 mm Hg (n = 457), Q2: 165-175 mm Hg (n = 508), Q3: 180-195 mm Hg (n = 545) and Q4: 200-275 mm Hg (n = 489). After 35-years follow-up, there was a significant association between exercise SBP at baseline and cardiovascular disease and mortality. In the multivariate analysis adjusting for resting SBP, age, smoking status, total serum cholesterol and family history of coronary heart disease, as well as physical fitness, there is a 1.39-fold (CI: 1.00-1.93, p = 0.05) increased risk of cardiovascular mortality in Q4 compared to Q1. When not adjusting for physical fitness, there is a 1.29-fold (CI: 1.03-1.61, p = 0.02) increase in risk of cardiovascular disease between Q1 and Q4. CONCLUSIONS: The results of this study suggest that the association between exercise SBP at moderate workload and cardiovascular disease and mortality in middle-aged men extends through as long as 35 years and into old ages.

Apparent treatment-resistant hypertension - patient-physician relationship and ethical issues.

BACKGROUND: Poor drug adherence is a major cause of apparent treatment-resistant hypertension. As a consequence, several methods have been developed and attempted implemented in clinical practice to reveal non-adherence and to monitor drug adherence. There are, however, several hitherto unresolved ethical aspects regarding potential methods for drug monitoring in these patients. RESULTS: The most striking challenge is the balance between patient autonomy and the physician's desire for the patient to adhere to the prescribed therapy. Also, methods for monitoring must only be implemented in the treatment of well-informed and consenting patients. Major resources are used on non-adherent patients; how long the physician should encourage continuation of treatment is an important question. CONCLUSIONS: We believe that physicians should reflect and discuss these potential challenges, and that patient education, information and a solid patient-physician relationship are essential for achieving drug adherence. Methods for monitoring adherence represent, however, a useful and often necessary supplement.

A Case for Less Intensive Blood Pressure Control: It Matters to Achieve Target Blood Pressure Early and Sustained Below 140/90mmHg.

Although high blood pressure (BP) is the leading risk factors for cardiovascular (CV) disease, the optimal BP treatment target in order to reduce CV risk is unclear in the aftermath of the SPRINT study. The aim of this review is to assess large, randomized, and controlled trials on BP targets, as well as review selected observational analyses from other large randomized BP trials in order to evaluate the benefit of intense vs. standard BP control. None of the studies, except SPRINT, favored intense BP treatment. Some of the studies suggested favorable effects of lowering treatment target in patients with diabetes or high risk of stroke. In SPRINT, a new BP measurement method was introduced, and the results must be interpreted in light of this. The results of the observational analyses indicated the best preventive effect when achieving early and sustained BP control rather than low targets. In conclusion, today's guidelines' recommended treatment target of <140/90mmHg seems sufficient for most patients. Early and sustained BP control should be the main focus.