Julian E. Mariampillai

Tertiary work-up of apparent treatment-resistant hypertension

Abstract Objective: Treatment-resistant hypertension (TRH) has regained attention with development of new methods for treatment. However, the prevalence of TRH varies considerably from primary to secondary and tertiary care. We aimed to assess the prevalence of true TRH in a population of patients with apparent TRH in a university hospital setting of tertiary work-up and also investigate reasons for poor BP control and evaluate how work-up can be performed in general practice and secondary care. Methods: In this cohort study, we characterize a study population from Oslo Renal Denervation (RDN) Study. Patients (n = 83) were referred for RDN from secondary care. All patients underwent thorough medical investigation and 24-h ambulatory blood pressure measurements (24ABPM) after directly observed therapy (DOT). We then assessed reasons for lack of BP control. Results: Fifty-three of 83 patients did not have true TRH. Main reasons for non-TRH were poor drug adherence (32%), secondary hypertension (30%) and white coat hypertension (15%). Forty-seven percent achieved blood pressure control after DOT with subsequent 24ABPM. There were otherwise no statistically significant differences in patient characteristics between the true TRH and the non-TRH group. Conclusion: Despite being a highly selected cohort referred for tertiary work-up of apparent TRH, BP control was achieved or secondary causes were identified in almost two thirds of the patients. Thorough investigation according to guidelines and DOT with subsequent 24ABPM is needed in work-up of apparent TRH.

2D.01: EXERCISE SYSTOLIC BLOOD PRESSURE >/=190 MMHG AT MODERATE WORKLOAD PREDICTS CORONARY HEART DISEASE IN HEALTHY, MIDDLE-AGED MEN.

Objective: A hypertensive response to exercise at moderate workload is associated with future risk of coronary heart disease (CHD) and mortality. Yet there is still no consensus regarding the cut-off value for an inappropriate increase in exercise systolic blood pressure. We have previously shown that exercise blood pressure at 100W workload (SBP100W) > 200 mmHg is associated with increased risk of CHD and mortality. We now aimed to investigate the possible association between SBP100W >/= 190mmHg and risk of CHD over up to 28 years follow-up. Design and method: Of the 1999 apparently healthy, middle-aged men who underwent thorough medical examination and laboratory testing, including a symptom-limited bicycle ergometer test, during 1972–1975, 1392 men were still healthy at survey 2 seven years later and completed a workload of 100 W at both surveys. Systolic blood pressure was measured near completion of the 100W stage (SBP100W). By comparing subjects having SBP100W >/=190 mmHg at baseline, follow-up or both(n=365) with subjects having SBP100W < 190 mmHg at both surveys (n = 1027), we estimated the risk of CHD (angina pectoris, non-fatal myocardial infarction and death from coronary heart disease). Results: The combined endpoint of CHD occurred in 452 of the 1392 men; 243 events among the 365 men with SBP100W >/= 190 mmHg. When adjusting for survey 1 smoking status, age, systolic blood pressure at rest, total cholesterol and family history of coronary heart disease, there was a 1.38-fold (CI 1.11–1.71, p < 0.005) increased risk of CHD. When further adjusting for physical fitness, SBP100W >/=190mmHg was associated with a 1.35-fold (1.08–1.65) increased risk of CHD. Conclusions: Our findings indicate that a systolic blood pressure of 190 mmHg or more at moderate workload is associated with future risk of CHD among apparently healthy middle-aged men. Figure. No caption available.

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

Abstract 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.

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

Abstract 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.

ELEVATED SYSTOLIC BLOOD PRESSURE AT MIDDLE-AGE REMAINS A SIGNIFICANT CARDIOVASCULAR RISK FACTOR THROUGHOUT LIFE

Objective: Systolic blood pressure, prevalence of smoking, family history of coronary heart disease, cholesterol and cardiorespiratory fitness are well established as cardiovascular risk factors. In the present study we aimed to investigate how one measurement these variables at middle-age influenced risk of cardiovascular death during the first, intermediate and late part of a 35-year observation period, respectively. Figure. No caption available. Design and method: Systolic blood pressure, prevalence of smoking, family history of coronary heart disease, cholesterol and cardiorespiratory fitness were measured in 2014 apparently healthy, middle-aged Caucasian men by clinical examination, blood tests and an ECG-monitored, symptom-limited bicycle test. End points were registered after 35 years in a nationwide scrutiny of charts in all hospitals, and from the national Cause of Death registry. Early cardiovascular death was defined as event before 12 years of observation, intermediate event between 12 and 23 years of observation and late event between 23 and 35 years of observation. Impact of predictors and relative risks were estimated using Cox proportional hazards models. When estimating risks of intermediate and late cardiovascular death, men who died within 12 and 23 years were excluded. Results: We found 80 events of early, 207 events of intermediate and 241 events of late cardiovascular death. Age, systolic blood pressure, smoking status, and cholesterol were significant predictors of early, intermediate and late cardiovascular death. Baseline physical fitness was a significant and independent predictor of early and a borderline significant predictor of intermediate cardiovascular death but had no predictive impact on late cardiovascular death. Family history of coronary heart disease was a significant and independent predictor of early and intermediate, but not late cardiovascular death (Table1). Conclusions: Systolic blood pressure, smoking, and cholesterol measured at a median age 49 years were strong predictors of early, intermediate and late cardiovascular death during 35 years. Physical fitness at middle age and family history of coronary heart disease were only associated with risk of cardiovascular death before reaching 72 years. Risk factors for CV death have different persistence throughout life and systolic blood pressure at middle-age remains a significant cardiovascular risk factor until old ages.

IMPACT OF EXERCISE BLOOD PRESSURE ON STROKE RISK IN PHYSICALLY FIT AND UNFIT MEN. RESULTS FROM 35 YEARS FOLLOW-UP OF HEALTHY MIDDLE-AGED MEN

Objective: Resting blood pressure is one of the major risk factors for stroke. Our group recently showed that maximal blood pressure during exercise testing is a strong predictor of stroke in this cohort, independently of resting blood pressure. In the present study we investigate if maximal systolic blood pressures ability to predict stroke is influenced by a persons level of cardiorespiratory fitness. Design and method: The study enrolled 2014 healthy men aged 40–59 years between 1972–1975. The baseline examination included a maximal exercise test and the men were followed for a total of 35 years. Data on first-time stroke were collected from follow-up visits, hospital medical records from all national hospitals, and the national Cause of Death Registry. For data analyses, we grouped the men according to high or low fitness level (above/below median, values adjusted for age) and further for quartiles of maximal blood pressure. Multi-adjusted Cox regression analyses (including adjustment for resting blood pressure) were used to estimate risks for stroke. Results: During a median follow-up of time 31.9 years 316 first-time strokes occurred. There were no losses to follow-up. Fitness levels correlated positively with maximal systolic blood pressure. Among men with high fitness level, the highest quartile of maximal blood pressure had a higher risk of stroke than the lowest quartile (hazard ratio 1.75, confidence interval 1.06–2.94, p = 0.03). Among men with low fitness level, the highest quartile of maximal systolic blood pressure had a non-significantly higher risk of stroke than the lowest quartile (hazard ratio 1.50, confidence interval 0.91–2.63, p = 0.11). When resting systolic blood pressure was omitted from the models, maximal systolic blood pressure predicted stroke significantly in both fit and unfit men. Figure. No caption available. Conclusions: In healthy middle-aged men, maximal systolic blood pressure predicted stroke in men with high cardiorespiratory fitness, independently of resting systolic blood pressure. In men with low cardiorespiratory fitness the association was not significant, but there was no evidence of a qualitative different effect in this subgroup, and further research is needed to assess if maximal blood pressure has a predictive value for stroke in men, independently of fitness levels.

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.