Prevalence of potential modifiable factors of hypertension in patients with difficult-to-control hypertension.

BACKGROUND: A comprehensive diagnostic evaluation of potential modifiable factors of difficult-to-control hypertension would enable clinicians to target-specific amendable causes. Therefore, we assessed the prevalence of underlying medical conditions, lifestyle factors, and concomitant medication use in an integrated diagnostic evaluation in patients with difficult-to-control hypertension, referred to a tertiary center. METHODS: The study population consisted of 653 patients referred between 2006 and 2016 for difficult-to-control hypertension to the University Medical Center Utrecht. Difficult-to-control hypertension was defined by not reaching blood pressure (BP) goals despite BP-lowering drug use, or high office BP (>160/100 mmHg) without BP-lowering drug use. Patients were evaluated according to a highly standardized protocol including 24-h ambulatory blood measurements after cessation of BP-lowering drugs, 24-h urine sample, and a isotonic (0.9%) saline infusion test. RESULTS: In 621 patients (95%) one or more modifiable factors related to hypertension were identified (mean 2.1, SD 1.1). Obesity-related insulin resistance was the most common underlying medical condition which was diagnosed in 130 patients (20%). Primary aldosteronism was diagnosed in 40 patients (6%) and obstructive sleep apnea in 17 patients (3%). Sodium intake was deemed to high (urinary excretion of >6 g/day) in 433 patients (66%). In total, 283 patients (43%) were physical inactive (<30 min/day, during 5 days/week). Oral contraceptive-related hypertension was diagnosed in 10 women (3% of women). CONCLUSION: In patients with difficult-to-control hypertension there is a high prevalence of potential modifiable factors related to hypertension, highlighting the importance for an integrated diagnostic evaluation.

Apparent resistant hypertension and the risk of vascular events and mortality in patients with manifest vascular disease.

OBJECTIVE: Patients with apparent resistant hypertension (aRH) are at increased risk for developing cardiovascular disease. It is unknown if this condition is related to increased cardiovascular risk in patients with clinically manifest vascular disease. METHODS: In 6191 hypertensive patients with clinically manifest vascular disease, we evaluated the risk of subsequent vascular events and mortality between patients with controlled hypertension, uncontrolled hypertension, controlled aRH, and uncontrolled aRH. Controlled aRH was defined as office blood pressure less than 140/90 mmHg while using at least four antihypertensive drugs. Uncontrolled aRH was defined as office blood pressure at least 140/90 mmHg while using three antihypertensive drugs including a diuretic, or at least four antihypertensive drugs. Outcomes of interest were myocardial infarction, stroke, cardiovascular mortality, the composite outcome of cardiovascular events, and all-cause mortality. RESULTS: In total 2564 patients (41%) had controlled hypertension, 3063 patients (49%) had uncontrolled hypertension, 123 patients (2%) had controlled aRH, and 411 patients (7%) had uncontrolled aRH. During 7.1 years of follow-up patients with controlled aRH were at a higher risk of cardiovascular mortality [hazard ratios 1.86; 95% confidence interval (CI) 1.10-3.15], and all-cause mortality (hazard ratios 1.64; 95% CI 1.07-2.52) compared with patients with controlled hypertension. Patients with uncontrolled aRH were at a higher risk of cardiovascular mortality (hazard ratios 1.36; 95% CI 1.01-1.83), and higher risk of all-cause mortality (hazard ratios 1.27; 95% CI 1.01-1.60) compared with patients with controlled hypertension. CONCLUSION: In hypertensive patients with clinically manifest vascular disease, presence of controlled and uncontrolled aRH is related to an increased risk of cardiovascular mortality and all-cause mortality.

Safety of Temporary Discontinuation of Antihypertensive Medication in Patients With Difficult-to-Control Hypertension.

Successful control of blood pressure relies on identification of secondary causes and contributing factors of hypertension. As antihypertensive medication can interfere with diagnostic investigations, temporary discontinuation of medication is advised. However, there are concerns about the safety of temporary discontinuation of antihypertensive medication in patients with difficult-to-control hypertension. We assessed the occurrence of adverse cardiovascular and cerebrovascular events potentially attributable to temporary discontinuation of antihypertensive medication between February 2010 and March 2016 (n=604) in our Analysis of Complicated Hypertension screening program. A reference group (n=604) was extracted from the SMART study (Second Manifestations of Arterial Disease) cohort (comprising a similar cohort at our hospital in whom medication was not stopped) and individually matched for blood pressure, age, sex, and history of cardiovascular disease. Discontinuation of medication was well tolerated; 62% reported no complaints, 24% had mild discomfort that could be left untreated, and 14% experienced complaints that required prescription of antihypertensive escape medication. Three major adverse events were observed in the Analysis of Complicated Hypertension group between discontinuation of medication and 30 days after restart of medication (event rate=31.2 events per 1000 patient-year). In the reference cohort, 5 cardiovascular events were observed during a similar follow-up period (event rate=51.2 events per 1000 patient-year). In conclusion, discontinuation of antihypertensive medication for the diagnostic evaluation of hypertension does not increase the acute risk of cardiovascular events when performed in a well-controlled setting in specialized hospitals with appropriate protocols for monitoring safety.

Relation between Kidney Length and Cardiovascular and Renal Risk in High-Risk Patients.

BACKGROUND AND OBJECTIVES: Kidney length is often measured during routine abdominal ultrasonography and may be of use to identify patients at high vascular and renal risk. We aimed to explore patient characteristics related to kidney length, from which reference values were derived, and evaluate the relationship between kidney length and the risk of cardiovascular events and ESRD in high-risk patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study population consisted of 10,251 patients with clinical manifest arterial disease or vascular risk factors included in the Second Manifestations of ARTerial disease (SMART) Study cohort between 1996 and 2014. Linear regression was used to explore patient characteristics of kidney length. The relationship between kidney length and cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality), all-cause mortality, and ESRD was analyzed using Cox regression. Kidney length was analyzed in tertiles, using the second tertile as the reference category. RESULTS: Kidney length was strongly correlated with body surface area (2.04 mm; 95% confidence interval [95% CI], 1.95 to 2.13 per 0.1 m2 increase) and eGFR (1.62 mm; 95% CI, 1.52 to 1.73 per 10 ml/min per 1.73 m2 increase). During the median follow-up of 6.3 years, 1317 patients experienced a cardiovascular event, including 711 myocardial infarctions, 369 strokes, and 735 vascular cause deaths. A total of 1462 patients died of any cause and 52 patients developed ESRD. Irrespective of eGFR, patients in the third tertile of kidney length (11.7-16.1 cm) were at higher risk of cardiovascular mortality (hazard ratio, 1.33; 95% CI, 1.05 to 1.67) and cardiovascular events (hazard ratio, 1.28; 95% CI, 1.09 to 1.50). Patients in the first tertile of kidney length (7.8-10.8 cm) were not at higher risk of cardiovascular adverse events. CONCLUSIONS: Large kidney length is related to higher risk of cardiovascular events and mortality in high-risk patients, irrespective of eGFR. Kidney length may serve as a clinical marker to further identify patients at high cardiovascular risk.

Prevalence and clinical characteristics of apparent therapy-resistant hypertension in patients with cardiovascular disease: a cross-sectional cohort study in secondary care.

OBJECTIVES: Our aim was to investigate the prevalence of apparent therapy-resistant hypertension (aTRH) in patients with clinical manifest cardiovascular disease (CVD), and to study clinical characteristics related to aTRH in this population. SETTING: The SMART (Second Manifestations of ARTerial disease) study is a large, single-centre cohort study in secondary care. PARTICIPANTS: Office blood pressure (BP) at inclusion was used to evaluate BP control in 6191 hypertensive patients with clinical manifest (cardio)vascular disease. Therapy-resistant hypertension was defined as BP ≥140/90 mm Hg despite use of antihypertensive drugs from ≥3 drug classes including a diuretic or use of ≥4 antihypertensive drugs irrespective of BP. Logistic regression analysis was used to explore the relationship between clinical characteristics measured at baseline and presence of aTRH. RESULTS: The prevalence of aTRH was 9.1% (95% CI 8.4 to 9.8). Prevalence increased with age and when albuminuria was present and was higher in patients with lower estimated glomerular filtration rate (eGFR). Presence of aTRH was related to diabetes, female sex, duration and multiple locations of vascular disease, body mass index and waist circumference. Carotid intima-media thickness was higher (0.99±0.28 vs 0.93±0.28 mm) and ankle-brachial index lower (1.07±0.20 vs 1.10±0.19) in patients with aTRH compared with patients without aTRH. CONCLUSION: aTRH is prevalent in patients with clinical manifest CVD and is related to clinical factors known to be related with increased vascular risk, and with lower eGFR.