Treatment of hypertension in patients with peripheral arterial disease: an update.

Hypertension is a known risk factor for cardiovascular events, and recent data have pointed to peripheral arterial disease (PAD) as another strong risk factor; together, they cause a surprisingly high total risk. This review deals with the clinical management of this dangerous association. The ankle-brachial index helps in the diagnosis of PAD and the estimation of risk. To control risk, lifestyle adaptation is essential. There is no consensus on a first choice of antihypertensive drug. Arguments favor angiotensin-converting enzyme inhibitors, but most patients require several antihypertensive drugs to reach goal pressure (140/90 mm Hg or lower). Moreover, to control the risk of PAD, antiplatelet drugs, antihypertensive drugs, and statins are recommended.

Prognostic Value of Masked Uncontrolled Hypertension.

The prognostic relevance of masked uncontrolled hypertension (MUCH) is incompletely clear, and its global impact on cardiovascular outcomes and mortality has not been assessed. The aim of this study was to perform a meta-analysis on the prognostic value of MUCH. We searched for articles assessing outcome in patients with MUCH compared with those with controlled hypertension (CH) and reporting adjusted hazard ratio and 95% CI. We identified 6 studies using ambulatory blood pressure monitoring (12 610 patients with 933 events) and 5 using home blood pressure measurement (17 742 patients with 394 events). The global population included 30 352 patients who experienced 1327 events. Selected studies had cardiovascular outcomes and all-cause mortality as primary outcome, and the main result is a composite of these events. The overall adjusted hazard ratio was 1.80 (95% CI, 1.57-2.06) for MUCH versus CH. Subgroup meta-analysis showed that adjusted hazard ratio was 1.83 (95% CI, 1.52-2.21) in studies using ambulatory blood pressure monitoring and 1.75 (95% CI, 1.38-2.20) in those using home blood pressure measurement. Risk was significantly higher in MUCH than in CH independently of follow-up length and types of studied events. MUCH was at significantly higher risk than CH in all ethnic groups, but the highest hazard ratio was found in studies, including black patients. Risk of cardiovascular events and all-cause mortality is significantly higher in patients with MUCH than in those with CH. MUCH detected by ambulatory or home blood pressure measurement seems to convey similar prognostic information.

2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension.

: Document reviewers: Guy De Backer (ESC Review Co-ordinator) (Belgium), Anthony M. Heagerty (ESH Review Co-ordinator) (UK), Stefan Agewall (Norway), Murielle Bochud (Switzerland), Claudio Borghi (Italy), Pierre Boutouyrie (France), Jana Brguljan (Slovenia), Héctor Bueno (Spain), Enrico G. Caiani (Italy), Bo Carlberg (Sweden), Neil Chapman (UK), Renata Cifkova (Czech Republic), John G. F. Cleland (UK), Jean-Philippe Collet (France), Ioan Mircea Coman (Romania), Peter W. de Leeuw (The Netherlands), Victoria Delgado (The Netherlands), Paul Dendale (Belgium), Hans-Christoph Diener (Germany), Maria Dorobantu (Romania), Robert Fagard (Belgium), Csaba Farsang (Hungary), Marc Ferrini (France), Ian M. Graham (Ireland), Guido Grassi (Italy), Hermann Haller (Germany), F. D. Richard Hobbs (UK), Bojan Jelakovic (Croatia), Catriona Jennings (UK), Hugo A. Katus (Germany), Abraham A. Kroon (The Netherlands), Christophe Leclercq (France), Dragan Lovic (Serbia), Empar Lurbe (Spain), Athanasios J. Manolis (Greece), Theresa A. McDonagh (UK), Franz Messerli (Switzerland), Maria Lorenza Muiesan (Italy), Uwe Nixdorff (Germany), Michael Hecht Olsen (Denmark), Gianfranco Parati (Italy), Joep Perk (Sweden), Massimo Francesco Piepoli (Italy), Jorge Polonia (Portugal), Piotr Ponikowski (Poland), Dimitrios J. Richter (Greece), Stefano F. Rimoldi (Switzerland), Marco Roffi (Switzerland), Naveed Sattar (UK), Petar M. Seferovic (Serbia), Iain A. Simpson (UK), Miguel Sousa-Uva (Portugal), Alice V. Stanton (Ireland), Philippe van de Borne (Belgium), Panos Vardas (Greece), Massimo Volpe (Italy), Sven Wassmann (Germany), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain).The disclosure forms of all experts involved in the development of these Guidelines are available on the ESC website www.escardio.org/guidelines.

Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension.

BACKGROUND: It is uncertain whether ambulatory blood-pressure measurements recorded for 24 hours in patients with treated hypertension predict cardiovascular events independently of blood-pressure measurements obtained in the physician's office and other cardiovascular risk factors. METHODS: We assessed the association between base-line ambulatory blood pressures in treated patients and subsequent cardiovascular events among 1963 patients with a median follow-up of 5 years (range, 1 to 66 months). RESULTS: We documented new cardiovascular events in 157 patients. In a Cox proportional-hazards model with adjustment for age, sex, smoking status, presence or absence of diabetes mellitus, serum cholesterol concentration, body-mass index, use or nonuse of lipid-lowering drugs, and presence or absence of a history of cardiovascular events, as well as blood pressure measured at the physician's office, higher mean values for 24-hour ambulatory systolic and diastolic blood pressure were independent risk factors for new cardiovascular events. The adjusted relative risk of cardiovascular events associated with a 1-SD increment in blood pressure was 1.34 (95 percent confidence interval, 1.11 to 1.62) for 24-hour ambulatory systolic blood pressure, 1.30 (95 percent confidence interval, 1.08 to 1.58) for ambulatory systolic blood pressure during the daytime, and 1.27 (95 percent confidence interval, 1.07 to 1.57) for ambulatory systolic blood pressure during the nighttime. For ambulatory diastolic blood pressure, the corresponding relative risks of cardiovascular events associated with a 1-SD increment were 1.21 (95 percent confidence interval, 1.01 to 1.46), 1.24 (95 percent confidence interval, 1.03 to 1.49), and 1.18 (95 percent confidence interval, 0.98 to 1.40). CONCLUSIONS: In patients with treated hypertension, a higher ambulatory systolic or diastolic blood pressure predicts cardiovascular events even after adjustment for classic risk factors including office measurements of blood pressure.

Predictive value of clinic and ambulatory heart rate for mortality in elderly subjects with systolic hypertension.

OBJECTIVE: To examine the association of clinic and ambulatory heart rate with total, cardiovascular, and noncardiovascular death in a cohort of elderly subjects with isolated systolic hypertension from the Systolic Hypertension in Europe Trial. METHODS: A total of 4682 patients participated, whose untreated blood pressure on conventional measurement at baseline was 160 to 219 mm Hg systolic and lower than 95 mm Hg diastolic. Clinic heart rate was the mean of 6 readings during 3 visits. Ambulatory heart rate was recorded with a portable intermittent technique in 807 subjects. RESULTS: Raised baseline clinic heart rate was positively associated with a worse prognosis for total, cardiovascular, and noncardiovascular mortality among the 2293 men and women taking placebo. Subjects with heart rates higher than 79 beats/min (bpm) (top quintile) had a 1.89 times greater risk of mortality than subjects with heart rate lower than or equal to 79 bpm (95% confidence interval, 1.33-2.68 bpm). In a Cox regression analysis, predictors of time to death were heart rate (P<.001), age (P<.001), serum creatinine level (P =.001), presence of diabetes (P =.002), previous cardiovascular disease (P =.01), triglyceride readings (P =.02), smoking (P =.04), and elevated systolic blood pressure (P =.05), while total cholesterol level was found to be nonsignificant in the model. In the ambulatory monitoring subgroup, clinic and ambulatory heart rates predicted noncardiovascular but not cardiovascular mortality. However, in a Cox regression analysis in which clinic and ambulatory heart rates were included, a significant association with noncardiovascular mortality was found only for clinic heart rate (P =.004). In the active treatment group, the weak predictive power of clinic heart rate for mortality disappeared after adjustment for confounders. CONCLUSIONS: In untreated older patients with isolated systolic hypertension, a clinic heart rate greater than 79 bpm was a significant predictor of all-cause, cardiovascular, and noncardiovascular mortality. Ambulatory heart rate did not add prognostic information to that provided by clinic heart rate.

Hypertension in peripheral arterial disease.

Peripheral arterial disease (PAD) of the lower limbs is associated with a high cardiovascular morbidity and mortality. Intermittent claudication is the most common symptomatic manifestation of PAD, but is in its own value an important predictor of cardiovascular death, increasing it by three-fold, and increasing all-cause mortality by two-to-five fold. Hypertension is a risk factor for vascular disorders, including PAD. Of hypertensives at presentation, about 2-5% have intermittent claudication, with increasing prevalence with age. Otherwise, 35-55% of patients with PAD at presentation also show hypertension. Patients who suffer from hypertension with PAD have a greatly increased risk of myocardial infarction and stroke. There is no consensus on the specific treatment of hypertension in PAD because of the limited controlled studies on antihypertensive therapy in such specific PAD population. There is an obvious need of such outcome studies, especially since the two conditions are frequently encountered together. However, as risk is high in all PAD patients, the most important goal remains to decrease the global cardiovascular risk in such patients rather than to focus on the control of blood pressure only and on the reduction of symptoms of PAD. Therefore, treatment with antiplatelet drugs, ACE-inhibitors and statins should be considered.

High prevalence of peripheral arterial disease in hypertensive patients: the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives screening program.

AIMS: Peripheral arterial disease (PAD) can be diagnosed in asymptomatic stage, measuring ankle-brachial index (ABI). Low ABI is an indicator of increased cardiovascular risk and its inclusion to traditional risk factors can improve risk prediction. The objective of the present cross-sectional part of our large-scale, multicenter, observational study was to evaluate the prevalence of PAD in a large cohort of hypertensive patients. METHODS AND RESULTS: A total of 21 892 hypertensive men and women (9162 men; mean age 61.45 years) were included in our prospective study in hypertension clinics. Clinical history, physical examination, and blood analysis were taken, and the ABI was measured with the Doppler method in all patients. The prevalence of PAD (ABI ≤ 0.9) was 14.4%. In 15.6% of the patients an ABI of 0.91-0.99, and in 9.4% of the patients high ABI (>1.3) was measured. In the low, moderate, high, and very high Systematic Coronary Risk Evaluation risk groups, the prevalence of low ABI was 8.1, 11.1, 16.3, and 26%, respectively. The prevalence of PAD was lower in hypertensive patients achieving their blood pressure target (9.6 vs. 16.8%; P < 0.001). CONCLUSIONS: Asymptomatic PAD was highly prevalent in the studied hypertensive population. The use of ABI screening may improve cardiovascular risk prediction. Optimal blood pressure goal values in PAD patients and cardiovascular morbidity/mortality data will be evaluated after the 5-year long prospective phase of the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives program.

Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension.

Our aim was to assess the prognostic significance of nighttime and daytime ambulatory blood pressure and their ratio for mortality and cause-specific cardiovascular events in hypertensive patients without major cardiovascular disease at baseline. We performed a meta-analysis on individual data of 3468 patients from 4 prospective studies performed in Europe. Age of the subjects averaged 61+/-13 years, 45% were men, 13.7% smoked, 8.4% had diabetes, and 61% were under antihypertensive treatment at the time of ambulatory blood pressure monitoring. Office, daytime, and nighttime blood pressure averaged 159+/-20/91+/-12, 143+/-17/87+/-12, and 130+/-18/75+/-12 mm Hg. Total follow-up amounted to 23 164 patient-years. We used multivariable Cox regression analysis to assess the hazard ratios associated with 1 standard deviation higher blood pressure. Daytime and nighttime systolic blood pressure predicted all-cause and cardiovascular mortality, coronary heart disease, and stroke, independently from office blood pressure and confounding variables. When these blood pressures were entered simultaneously into the models, nighttime blood pressure predicted all outcomes, whereas daytime blood pressure did not add prognostic precision to nighttime pressure. Appropriate interaction terms indicated that the results were similar in men and women, in younger and older patients, and in treated and untreated patients The systolic night-day blood pressure ratio predicted all outcomes, which only persisted for all-cause mortality after adjustment for 24-hour blood pressure. In conclusion, nighttime blood pressure is in general a better predictor of outcome than daytime pressure in hypertensive patients, and the night-day blood pressure ratio predicts mortality, even after adjustment for 24-hour blood pressure.

Prognostic significance of ambulatory blood pressure in hypertensive patients with history of cardiovascular disease.

OBJECTIVE: To assess the prognostic significance of nighttime and daytime blood pressure (BP), their ratio and the nighttime dipping pattern for mortality and recurrent cardiovascular (CV) events in patients with CV disease at baseline. BACKGROUND: The prognostic value of ambulatory BP has not been reported in hypertensive patients with a history of CV disease. METHODS: We performed a meta-analysis on individual data of 302 patients with hypertension and CV disease from three prospective studies performed in Europe. RESULTS: Age of the patients averaged 69+/-9 years; 50% were men and 62% were under antihypertensive treatment at the time of ambulatory BP monitoring. Office, daytime and nighttime BP averaged 161+/-20/86+/-12, 144+/-16/83+/-11 and 132+/-18/72+/-12 mmHg. Total follow-up time amounted to 2049 patient--years. Multivariable Cox regression analysis revealed that nighttime BP, but not daytime BP significantly predicted CV mortality (P< or =0.05) and major CV events (P< or =0.01) after adjustment for office BP and other confounders. When both nighttime and daytime BP were entered into the models, the predictive power of nighttime BP remained significant (P< or =0.05); daytime BP did not add prognostic precision to nighttime BP. The systolic nightday BP ratio predicted all outcomes, and outcome was significantly worse in reverse dippers and nondippers than in dippers, both before and after adjustment for 24-h BP (P< or =0.05). CONCLUSION: Nighttime BP is the better predictor of death and recurrent CV events in hypertensive patients with a history of CV disease. The night-day BP ratio and the dipping pattern significantly predict outcome, even after adjustment for 24-h BP.

How to treat hypertension in patients with peripheral artery disease.

The risk of peripheral artery disease is underestimated by many physicians; such risk is further augmented by the presence of hypertension. Detection of these conditions is essential to prevent cardiovascular accidents. This review deals with the management of peripheral artery disease as a risk factor, highlighting the need for triple therapy (antiplatelet drugs, angiotensin-converting enzyme inhibitors, and statins). Treatment of hypertension is approached by reviewing the essentials of the different antihypertensive drugs available, focusing on their peripheral circulatory effect. However, because individual antihypertensive drugs seem not to differ largely in this respect, attention is drawn to the message that the most important task in these patients is to control total cardiovascular risk rather than focusing on the choice of the individual antihypertensive drug.