Few issues of modern cardiovascular medicine have been as controversial as the relationship between white-coat hypertension (WCH), that is, a common condition in which office blood pressure is elevated while out-of-office blood pressure (ambulatory blood pressure or home blood pressure) is normal. While earlier studies showed no increased risk of cardiovascular events in WCH compared with the normotensive state, more recent studies have changed this conclusion by showing that an increased cardiovascular risk represents a trait of this hypertensive phenotype. The present article will review a number of issues related to WCH, that is, its definition, pathophysiological background, clinical alterations, and prognostic significance. This will be done by considering the available evidence published during the last decades, with special focus on the data collected in PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni)—a research project performed with a cross-sectional and longitudinal design, which has provided a series of novel clinical information on WCH throughout the years. The final part of the article will discuss the therapeutic implications of the abovementioned evidence, as well as some controversial or still undefined issues related to WCH, whose investigation will be an important goal to pursue by future research.

Limited information is available on office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients living in central and eastern European countries. In 2008, a survey on 7860 treated hypertensive patients followed by non-specialist or specialist physicians was carried out in nine central and eastern European countries (Albania, Belarus, Bosnia, Czech Republic, Latvia, Romania, Serbia, Slovakia, and Ukraine). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Patients had a mean (±SD) age of 60.1 ± 11 years, and the majority of them (83.5%) were followed by specialists. Average clinic BP was 149.3 ± 17/88.8 ± 11 mmHg. About 70% of patients displayed a very high-risk profile. Electrocardiogram was performed in 99% of patients, echocardiography in 65%, carotid ultrasound in 24%, fundoscopy in 68%, and search for microalbuminuria in 10%. Ambulatory BP monitoring was performed in about one-fifth of the recruited patients. Despite the widespread use of combination treatment (87% of the patients), office BP control (<140/90 mmHg) was achieved in 27.1% only, the corresponding control rate for ambulatory BP (<130/80 mmHg) being 35.7%. Blood pressure control was (i) variable among different countries, (ii) worse for systolic than for diastolic BP, (iii) slightly better in patients followed by specialists than by non-specialists, (iv) unrelated to patients’ age, and (v) more unsatisfactory in high-risk hypertensives and in patients with coronary heart disease, stroke, or renal failure. These data provide evidence that in central and eastern European countries office and ambulatory BP control are unsatisfactory, particularly in patients at very high CV risk, and not differ from that seen in Western Europe. They also show that assessment of subclinical organ damage is quite common, except for microalbuminuria, and that combination drug treatment is frequently used.

In 1722 hypertensives recruited for the European Lacidipine Study on Atherosclerosis and treated with atenolol or lacidipine (±additional drugs) during 4 years, we evaluated the long-term reproducibility of dipping, nondipping, extreme dipping, and reverse dipping, an information of key relevance for defining the prognostic impact of these blood pressure (BP) phenotypes. Ambulatory BP was measured at baseline and every year during treatment, allowing repeated classifications of these conditions. Based on systolic BP, at baseline 50.1%, 37.5 %, 4.5 %, and 7.9 % were dippers, nondippers, extreme dippers, and reverse dippers, respectively. Antihypertensive drug treatment reduced the number of dippers and extreme dippers in favor of nondippers and reverse dippers. During treatment, the dipping and nondipping phenotypes were markedly unstable and shifts from one to other phenotypes were even more common in reverse and extreme dippers In only a very small fraction of patients, a given nighttime BP phenotype was persistently found throughout the 4 years. Data were similar for diastolic BP and in subgroups differing for the type of treatment, the treatment complexity, and the achieved on-treatment BP value Poor reproducibility characterized also the absolute nighttime BP reduction as measured by the nighttime BP fall and the night/day BP ratio. Thus nighttime BP phenotypes are all largely inconsistent, their detection over the entire treatment period involving just a minute fraction of the entire patients’ cohort.

Compliance and distensibility of middle-sized conduit arteries are increased in hypertension and reduced in hypercholesterolemia. Despite their frequent association in the same individual, the combined effect of these two conditions on arterial mechanical properties is unknown. We studied four groups of age- and sex-matched subjects: 10 normotensive normocholesterolemic subjects, 10 mild hypertensive normocholesterolemic subjects, 10 mild hypercholesterolemic normotensive subjects, and 10 mild hypertensive and mild hypercholesterolemic subjects. We measured radial artery diameter by an echotracking device and beat-to-beat blood pressure from an ipsilateral finger. Compliance-pressure and distensibility-pressure curves were derived by Langewouters' formula. Between-group comparisons were made by calculating for both compliance and distensibility the integral of the area under the portion of the curve common to the four groups (“isobaric” compliance and distensibility). Blood pressure was similarly elevated in the two hypertensive groups, and serum cholesterol was similarly elevated in the two hypercholesterolemic groups. Compared with values in normotensive normocholesterolemic subjects, isobaric compliance and distensibility were greater in hypertensive normocholesterolemic (+38% and 47%, respectively) and smaller in normotensive hypercholesterolemic (−6% and −23%) subjects. However, when both hypertension and hypercholesterolemia were present, isobaric compliance and isobaric distensibility were significantly reduced (−26% and −18%, P <.05). Therefore, hypercholesterolemia reverses the effect of hypertension on arterial compliance and causes arterial stiffening, as when present alone.

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan–Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (≥4.7 mg/dL) and CVM (≥5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12–1.40], p < 0.001) and CVM (1.31 [1.11–1.74], p < 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12–1.43], p < 0.001) and hypertriglyceridemia (1.31 [1.02–1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23–1.73], p < 0.001) and hypertriglyceridemia (HR 1.31 [0.99–1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels.