Amyloid beta is associated with carotid wall echolucency and atherosclerotic plaque composition.

Circulating amyloid-beta 1-40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.

A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls.

Background: The arterial pathology and mechanisms of increased cardiovascular disease (CVD) risk in HCV-infected individuals are not yet clear. The aim of this study was to identify types of arterial pathology in treatment-naive chronic HCV patients and to test their reversibility after successful treatment. Methods: Consecutive, never-treated, HCV-infected patients were compared with age and CVD-related risk factors, matched controls, healthy individuals (HI), patients with rheumatoid arthritis (RA) and people living with HIV (PLWH), in terms of arterial stiffening by pulse wave velocity, arterial atheromatosis/hypertrophy by carotid plaques/intima-media thickness and impaired pressure wave reflections by augmentation index. After three months of sustained virological response (SVR) administered using direct-acting antivirals, vascular examination was repeated in HCV-infected patients to test drug and viral-elimination effect in subclinical CVD. Results: Thirty HCV patients were examined at baseline; fourteen of them were re-examined post-SVR. Compared with HI, HCV patients had significantly more plaques, which is similar to that of RA patients and the PLWH group. No other differences were found in all other vascular biomarkers, and regression among HCV patients also revealed no differences 3 months post-SVR. Conclusions: Accelerated atheromatosis, rather than arterial stiffening, arterial remodeling and peripheral impaired hemodynamics is the underlying pathology leading to increased CVD risk in HCV patients.

Systematic Breakfast Consumption of Medium-Quantity and High-Quality Food Choices Is Associated with Better Vascular Health in Individuals with Cardiovascular Disease Risk Factors.

BACKGROUND: Breakfast consumption has been associated with the improvement of many cardiovascular disease (CVD) risk factors, yet data regarding its association with subclinical vascular damage, which precedes the onset of CVD, are scarce. The aim of this study is to investigate this association in a large sample of adults with CVD risk factors. METHODS: Anthropometric measurements, vascular biomarkers and dietary intake with two 24-h dietary recalls, focusing on breakfast frequency and its quantity and content, were assessed in 902 adults (45.2% males). Breakfast quality was assessed by identifying a posteriori breakfast dietary pattern (DP) by using principal component analysis (PCA). RESULTS: Systematic breakfast consumption (SBC) was inversely associated with central systolic blood pressure (b: -3.28, 95% C.I.: -5.7 to -0.86), diastolic blood pressure (b: -1.85, 95% C.I.: -3.34 to -0.36), augmentation index (b: -3.17, 95% C.I.:-4.98 to 1.35) and left carotid intima media thickness (b: -0.03, 95% C.I.:-0.06 to -0.01) compared to breakfast skipping independently of age, sex, hypertension, diabetes, dyslipidemia, smoking, and BMI. SBC of 10-20% of daily total energy intake (dTEI) was inversely associated with Aix (b: -2.31, 95% C.I.:-4.05 to -0.57) compared to <10% dTEI after adjustment for the aforementioned confounders. DP1 (high coffee and sugar consumption, low consumption of low- and full-fat dairy products, fruits, and fresh juices) was positively associated with Aix (b: 1.19, 95% C.I.: 0.48 to 1.90). CONCLUSION: SBC comprised of medium-energy density and high-nutrient content food items may be a simple daily habit associated with better vascular health.

Association of Pressure Wave Reflections With Left Ventricular Mass: a Systematic Review and Meta-Analysis.

BACKGROUND: Pressure wave reflections (PWRs) within the circulation are assessed at various arterial sites by various noninvasive methods. We aimed at reviewing the conflicting data regarding the hypothesis that higher PWRs are associated with higher left ventricular mass and tested whether this association stands for all available indices of PWRs, all (proximal or distal to the heart) sites of assessment, and is modified by sex, age and heart rate. METHODS: Based on a predefined protocol applying the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we identified eligible for meta-analysis data regarding: augmentation index, augmentation pressure, backward pressure (Pb), reflection index, and their association with left ventricular mass index (19 studies, total population n=8686). RESULTS: We found statistically significant associations, independent from blood pressure level, for all indices of PWRs at all arterial sites (carotid augmentation index; odds ratio; standardized beta coefficient [ß]: 0.14 [95% CI, 0.07% to 0.21%], per SD increase), radial augmentation index (ß: 0.21; 0.11 to 0.31), central augmentation pressure (ß: 0.15; 0.03 to 0.27), central Pb (ß: 0.23; 0.05 to 0.42), and central reflection index (ß: 0.14; 0.06 to 0.22), except for aortic augmentation index as estimated by generalized transfer functions. Meta-regression analysis showed that the association between carotid augmentation index and left ventricular mass was higher among populations with higher heart rate (P=0.036, beta: 0.017 [95% CI, 0.001 to 0.033]) and tended to be higher in middle-aged (P=0.07, beta: -0.001; -0.021 to 0.001). CONCLUSIONS: A clinically meaningful association between PWRs and left ventricular mass, assessed at either central or peripheral arterial sites by most available methods was shown, suggesting that PWR reduction strategies might be useful. Based on the present evidence, such trials should target middle-aged populations with high normal heart rate.

Late-Night Overeating or Low-Quality Food Choices Late at Night Are Associated with Subclinical Vascular Damage in Patients at Increased Cardiovascular Risk.

Late-night overeating (LNO) is associated with several cardiovascular disease (CVD) risk factors. Limited data exist regarding the association between late-night (LN) systematic food consumption, LNO, and LN poor food quality with subclinical vascular damage (SVD) which precedes the onset of CVD. This study aimed to investigate the above associations with SVD in a large sample of adults, free of established CVD, with one or more CVD risk factors. In total, 901 adults (45.2% males) underwent anthropometric, dietary (through two 24 h dietary recalls) and vascular assessment. LN systematic eating was defined as consumption of food after 19:00 h in both dietary recalls and LNO was defined as systematic consumption of >40% of daily total energy intake (dTEI) after 19:00 h. Systematic LN food consumption was inversely associated with diastolic blood pressure (DBP) (−1.44 95% C.I. (−2.76, −0.12)) after adjusting for age, sex, hypertension, diabetes, dyslipidemia, smoking, BMI and dTEI. LNO was positively associated with existence of carotid plaques (1.70 95% C.I. (1.07, 2.68)), while LN increased consumption of red meat, refined grains and wine and low consumption of whole wheat grains was positively associated with Aix (Augmentation Index) (0.84 95% C.I. (0.09, 1.59)), after adjusting for all the mentioned confounders. Systematic LN eating is associated with lower DBP while systematic LNO and consumption of poor-quality food late at night, is associated with SVD. Further research is needed to define more accurately the impact of LN eating habits on vascular health.

Superiority of 24-Hour Aortic Over 24-Hour Brachial Pressure to Associate With Carotid Arterial Damage on the Basis of Pressure Amplification Variability: the SAFAR Study.

BACKGROUND: Evidence suggests marginal superiority of static aortic systolic blood pressure (aSBP) compared with brachial SBP (bSBP) regarding the association with organ damage and prognosis of cardiovascular disease (CVD). The noninvasive 24-hour aSBP assessment is feasible and associates better with presence of left ventricular hypertrophy compared with 24-hour bSBP. We aimed at comparing the association of 24-hour aSBP and 24-hour bSBP with indices of arterial damage and examining the role of 24-hour SBP amplification variability (within-subjects' SD) in this association. METHODS: Consecutive subjects referred for CVD risk assessment underwent 24-hour aortic and brachial ambulatory BP monitoring using a validated oscillometric device (Mobil-O-Graph). Arterial damage was assessed by carotid intima-media thickness (IMT) and detection of carotid and femoral atheromatosis (plaque presence). RESULTS: Cross-sectionally 501 individuals (aged 54±13 years, 57% men, 80% hypertensives) were examined. Multivariable analysis revealed superiority of 24-hour aSBP regarding the association with IMT, carotid hypertrophy and carotid-but not femoral-atheromatosis. In receiver operator characteristics analysis, 24-hour aSBP displayed a higher discriminatory ability-compared to 24-hour bSBP-for the detection of both carotid hypertrophy (area under the curve, 0.662 versus 0.624, P<0.05) and carotid atheromatosis (area under the curve, 0.573 versus 0.547, P<0.05). This effect was more prominent in individuals with above-median 24-hour SD of SBP amplification. CONCLUSIONS: Our results suggest that 24-hour aSBP assessment may be of significant value in clinical practice to detect site-specific arterial damage on the basis of pressure amplification variability and should be prospectively examined in clinical trials.

Dietary sodium estimation methods: accuracy and limitations of old and new methods in individuals at high cardiovascular risk.

OBJECTIVE: Accurate and easy to use methods for dietary Na intake estimation in population level are lacking. We aimed at (i) estimating the mean Na intake in the group level using a variety of dietary methods (DM) and urinary methods (UM) and correlating them with 24-h urine collection (24UCol) and (ii) improving the accuracy of the existing DM. DESIGN: The most common DM (three 24-h dietary recalls (24DR) and FFQ) and UM (24UCol and spot urine collection using common equations) were applied. To improve the existing: (i) 24DR, discretionary Na was quantified using salt-related questions or adding extra 15 % in total Na intake and (ii) FFQ, food items rich in Na and salt-related questions were added in the standard questionnaire (NaFFQ). SETTING: National and Kapodistrian University of Athens, Greece. PARTICIPANTS: Totally, 122 high cardiovascular risk subjects (56·0 ± 12·6 years; 55·7 % males). RESULTS: Mean 24 h Na excretion (24UNa) was 2810 ± 1304 mg/d. Spot urine methods overestimated the 24UNa (bias range: -1781 to -492 mg) and were moderately correlated to 24UCol (r = 0·469-0·596, P ≤ 0·01). DM underestimated the 24UNa (bias range: 877 to 1212 mg) and were weakly correlated with 24UCol. The improved DM underestimated the 24UNa (bias range: 877 to 923 mg). The NaFFQ presented the smallest bias (-290 ± 1336 mg) and the strongest correlation with 24UCol (r = 0·497, P ≤ 0·01), but wide limits of agreement in Bland-Altman plots (-2909 mg; 2329 mg), like all the other methods did. CONCLUSIONS: The existing methods exhibit poor accuracy. Further improvement of the newly developed NaFFQ could be promising for more accurate estimation of mean dietary Na intake in epidemiological studies. Additional validation studies are needed.

Dietary sugars and subclinical vascular damage in moderate-to-high cardiovascular risk adults.

BACKGROUND AND AIMS: The association between dietary sugars and vascular damage has been scarcely examined out of the context of established cardiovascular disease. We aimed to investigate the association between different types of sugars with subclinical atheromatosis and arteriosclerosis, in individuals free of cardiovascular disease being, however, at moderate-to-high cardiovascular risk. METHODS AND RESULTS: Two 24-h dietary recalls were conducted to estimate sugars intake. Subclinical atheromatosis was assessed by B-mode ultrasonography and arteriosclerosis (arterial stiffness) via tonometry (carotid-to-femoral pulse wave velocity). Multiple logistic regression analysis was performed to determine the relationship of quartiles of total sugars, monosaccharides and disaccharides with atheromatosis and arteriosclerosis, adjusting for potential confounders [Odds Ratio (95%Confidence Interval)]. In 901 participants (52.4 ± 13.8 years, 45.2% males), total sugars intake was not associated with any type of subclinical vascular damage. Subjects at 4th quartile of lactose intake (15.3 ± 5.5 g/day) had lower probability to present atheromatosis compared to those at 1st quartile (0.00 ± 0.01 g/day) even in the fully adjusted model [0.586 (0.353-0.974)]. Subjects at 3rd quartile of total disaccharides intake and particularly sucrose (15.1 ± 2.2 g/day) had higher probability to present arteriosclerosis compared to those at 1st quartile (3.0 ± 1.9 g/day) even after adjustment for all potential confounders [2.213 (1.110-4.409)]. CONCLUSIONS: Overall, the present data suggest a distinct role of each type of sugars on vascular damage. These observations highlight the need for further studies investigating not only foods rich in sugars, but sugars as separate components of food as they probably contribute via different ways on the development of arterial pathologies.

Association of gut microbiota composition and their metabolites with subclinical atheromatosis: A systematic review.

Study objective: The present systematic review investigates the hypothesis that specific components of the intestinal microbiome and/or their metabolites are associated with early stages of subclinical arterial damage (SAD). Design: Based on the MOOSE criteria, we conducted a systematic review of the literature (Scopus, Medline) investigating the potential association between gut microbiota and the most widely applied arterial biomarkers of SAD. Participants: All studies included individuals without established cardiovascular disease, either with or without SAD. Intervention: No interventions were made. Main outcome measures: Association between exposure (components/metabolites of microbiota) and outcome (presence of SAD). Results: Fourteen articles met the predefined criteria. Due to the large heterogeneity, their meta-analysis was not possible. Our review revealed (a) two studies on endothelial dysfunction, out of which one found an inverse relation between plasma trimethylamine N-oxide levels and FMD and the other did not substantiate a statistically significant correlation with RHI. (b) Twelve studies on atheromatosis, assessed as intimal-medial thickness (IMT), coronary artery calcium (CAC) and arterial plaque, of which, seven studies showed statistically significant associations (negative or positive depending on the microorganism or microbiota metabolite) with IMT, one study revealed significant associations with coronary artery calcium, while one showed absence of correlation and four studies reported statistically significant correlations with arterial plaque. (c) Three studies on arterial stiffness (pulse wave velocity - PWV) with two of them concluding in statistically significant association while the third study did not. Some articles investigated multiple of the correlations described and therefore, belonged to more than one section. Conclusion: Evidence of both positive and inverse associations of gut microbiota composition and their metabolites with different types of SVD has been found. However the small number and heterogeneity of available studies cannot allow to confirm or disprove the hypothesis.

Habitual consumption of instant coffee is favorably associated with arterial stiffness but not with atheromatosis.

OBJECTIVE: Epidemiological data suggest that moderate habitual coffee consumption associates with lower cardiovascular disease (CVD) risk; however scarce data exist regarding the association of coffee with subclinical vascular disease (SVD). We aimed at investigating the above association with habitual instant coffee consumption - a widely consumed coffee in Greece-in high CVD risk but free of established CVD adults. RESEARCH METHODS & PROCEDURES: In a cross-sectional design study we measured: (i) two 24 h dietary recalls to assess coffee consumption, (ii) arterial stiffness, by carotid to femoral pulse wave velocity - (PWV) and carotid compliance, arterial remodeling by carotid intima-media thickness (IMT), pressure wave reflection by augmentation index (AIx) and atheromatosis by carotid plaques. RESULTS: In 1041 participants (55.6% females, 53.6 ± 14.0 years), 30% habitually consumed instant coffee (0.53 ± 1.15 cups/day). Consumption of instant coffee was inversely associated with systolic blood pressure (ß = -1.19, p = 0.007), AIx (ß = -0.71, p = 0.043), PWV (ß = -0.22, p = 0.000) and IMT (ß = -0.01, p = 0.025), but these associations lost their significance after multiple adjustments for confounders. Instant coffee consumption was positively associated with carotid compliance independent from all possible confounders (ß = 0.005, p = 0.003). CONCLUSION: Habitual moderate instant coffee consumption is inversely associated with arterial stiffening and potential with arterial remodeling. These favorable vascular associations offer a potential pathophysiological link between habitual coffee consumption and lower incidence of CVD. Future studies are needed to examine the long-term effects of habitual instant coffee consumption on vascular structure and function.

Associations of dietary patterns with blood pressure and markers of subclinical arterial damage in adults with risk factors for CVD.

OBJECTIVE: Unhealthy diet is a modifiable risk factor leading to subclinical arterial damage (SAD), high BP and CVD. It was aimed to investigate the possible associations of dietary patterns (DPs) with SAD in adults having multiple CVD risk factors. DESIGN: Dietary intake was evaluated through two 24-h dietary recalls and principal component analysis was used to identify DPs. Oscillometry, applanation tonometry with pulse wave analysis and carotid ultrasound were used to assess peripheral and aortic BP, arterial stiffness and pressure wave reflections. SETTING: Laiko University Hospital, Athens, Greece. PARTICIPANTS: A total of 470 individuals (53·1 ± 14·2 years) with CVD risk factors were enrolled. RESULTS: A pattern characterised by increased consumption of whole-grain cereals, white meat and reduced consumption of sugar was positively associated with common carotid compliance (ß = 0·01, 95 % CI 0·00, 0·01), whereas a pattern high in refined cereals, red and processed meat was positively associated with brachial but not aortic systolic pressure (ß = 1·76, 95 % CI 0·11, 3·42) and mean arterial pressure (MAP) (ß = 1·18, 95 % CI 0·02, -2·38). Low consumption of low-fat dairy products, high consumption of full-fat cheese and butter was positively associated with MAP (ß = 0·97, 95 % CI 0·01, 1·95). Increased consumption of vegetables, fruits, fresh juices, fish and seafood was inversely associated with augmentation index (AIx) (ß = -1·01, 95 % CI -1·93, -0·09). CONCLUSION: Consumption of whole grains, white meat, fruits/vegetables, fish/seafood and avoidance of sugar was associated with improved SAD. Preference in refined grains, red/processed meat, high-fat cheese/butter and low intake of low-fat dairy products were associated with BP elevation. Future studies are needed to confirm the present findings.

Does Sodium Intake Induce Systemic Inflammatory Response? A Systematic Review and Meta-Analysis of Randomized Studies in Humans

Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect of high versus low sodium dose (HSD vs. LSD), as defined per study, on plasma circulating inflammatory biomarkers. Eight RCTs that examined CRP, TNF-a and IL-6 were found. Meta-analysis testing the change of each biomarker in HSD versus LSD was possible for CRP (n = 5 studies), TNF-a (n = 4 studies) and IL-6 (n = 4 studies). The pooled difference (95% confidence intervals) per biomarker was for: CRP values of 0.1(-0.3, 0.4) mg/L; TNF-a -0.7(-5.0, 3.6) pg/mL; IL-6 -1.1(-3.3 to 1.1) pg/mL. Importantly, there was inconsistency between RCTs regarding major population characteristics and the applied methodology, including a very wide range of LSD (460 to 6740 mg/day) and HSD (2800 to 7452 mg/day). Although our results suggest that the different levels of daily sodium intake are not associated with significant changes in the level of systemic inflammation in humans, this outcome may result from methodological issues. Based on these identified methodological issues we propose that future RCTs should focus on young healthy participants to avoid confounding effects of comorbidities, should have three instead of two arms (very low, "normal" and high) of daily sodium intake with more than 100 participants per arm, whereas an intervention duration of 14 days is adequate.

Dietary sodium and cardiovascular morbidity/mortality: a brief commentary on the 'J-shape hypothesis'.

The last decade, a growing number of evidence support J-shape or inverse - instead of positive linear -- associations between dietary sodium intake and cardiovascular morbidity/mortality. A careful evaluation of these studies leads to the following observations: less accurate methods for dietary sodium assessment are usually used; most studies included high-risk participants, enhancing the possibility of a 'reverse causality' phenomenon. However, these limitations do not explain all the findings. Few carefully designed randomized clinical trials comparing different levels of sodium intake that address the issue of the optimal and safe range exist; therefore, current guidelines recommend a higher cut-off instead of a safe range of intake. Given the demonstrated harmful effects of very low sodium diets leading to subclinical vascular damage in animal studies, the 'J-shape hypothesis' cannot yet be either neglected or verified. There is a great need of well-designed general population-based prospective randomized clinical trials to address the issue.

Levels of dietary sodium intake: diverging associations with arterial stiffness and atheromatosis.

BACKGROUND: Recent epidemiological evidence suggests a J-shaped, rather than the classical linear, association between dietary sodium (Na) intake and cardiovascular (CV) disease. Numerous animal studies have shown the acceleration of atheromatosis in a low-salt diet but data in humans are scarce. Our aim was to test the hypothesis that in a cohort of patients who are CV-free, yet at increased CV risk, moderate Na intake is associated with lower prevalence of atheromatosis and arterial stiffening than those at very low Na intake. METHODS: Two 24-h dietary recalls were conducted to estimate Na intake. Atheromatosis (carotid and femoral plaques) was assessed by B-mode ultrasonography and arterial stiffness through tonometry (carotid-to-femoral pulse wave velocity, cf-PWV). RESULTS: In 901 individuals (age: 52.4 ± 13.8 years, 45.2% males), only females at 3rd and 4th quartile of total Na intake (derived from food and discretionary salt) had significantly lower probability to present femoral plaques than those at 1st quartile (751.0 ± 215.5 mg/day), even in the full-adjusted model [0.462(0.229-0.935) and p = 0.032 3rd quartile; 0.274(0.118-0.638) and p = 0.003 4th quartile]. On the contrary, male and female individuals at 3rd quartile had significantly higher probability to present arterial stiffness (PWV >10 m/s) than those at 1st quartile [1.991(1.047-3.785) and p = 0.036]. CONCLUSIONS: Overall, the present data suggest that very low Na intake is associated with: a) accelerated atheromatosis, verifying findings from animal models, and providing a possible explanation of the modern epidemiology and b) lower arterial stiffness, which is in line with previous human findings, therefore suggesting a diverging effect of Na in the two major arterial pathologies.

Moderately increased alcohol consumption is associated with higher pressure wave reflections and blood pressure in men.

BACKGROUND AND AIMS: Increased alcohol consumption has been associated with CVD risk. Subclinical arterial damage (SAD) precedes the onset of cardiovascular disease (CVD), and allows early identification and study of the pathophysiology of CVD. Reliable, noninvasive vascular biomarkers are available for the early detection of SAD and reclassification of CVD risk. To investigate the association of alcohol consumption with multiple SAD biomarkers and central hemodynamics in a large sample of Greek adults with CVD risk factors. METHODS AND RESULTS: This cross-sectional study was conducted with 938 participants (43.5% men) and collected data on SAD biomarkers, central hemodynamics, and dietary intake. Multiple linear regression analysis was performed according to sex after adjusting for several confounders. In men, alcohol consumption of 20-30 g/d was positively associated with mean, diastolic, and peripheral systolic blood pressure (BP). The consumption of >30 g/d was positively associated with the augmentation index. In women, no statistically significant associations were found between alcohol consumption and BP or SAD indices. No statistically significant associations were found between alcohol consumption and arterial compliance or distensibility in both sexes. CONCLUSION: In men even a small deviation from the current recommendation for alcohol consumption is associated with both higher BP indices and pressure wave reflections. The absence of association in women might be due to very low alcohol intake, even in the high consumption group. More studies are needed to verify our findings and establish the above associations in each sex.

Contribution of single office aortic systolic blood pressure measurements to the detection of masked hypertension: data from two separate cohorts.

Masked hypertension (MH) and masked uncontrolled hypertension (MUH) remain largely underdiagnosed with no efficient detection algorithm. We recently proposed a novel classification of office systolic hypertension phenotypes defined on the basis of both brachial and aortic systolic blood pressure (bSBP/aSBP) and showed that type III ("isolated high office aSBP" phenotype: normal office bSBP but high office aSBP) has higher hypertension-mediated organ damage (HMOD). We tested whether MH/MUH (1) can be detected with the "isolated high office aSBP" phenotype and (2) if it is associated with elevated office aSBP with respect to normotension. We classified two separate and quite different cohorts (n = 391 and 956, respectively) on the basis of both bSBP and aSBP into four different phenotypes. Participants were classified as sustained hypertensives, masked hypertensives/masked uncontrolled hypertensives (MHs/MUHs), white coat hypertensives, and normotensives according to their office and out-of-office BP readings. The majority (more than 60% in cohort A and more than 50% in cohort B) of type III individuals were MHs/MUHs. Almost 35% of MHs/MUHs had optimal office bSBP rather than high normal bSBP. In both cohorts, the detection of more than 40% of MH/MUH was feasible with the type III phenotype. MHs/MUHs had higher office aSBP than individuals with sustained normotension (p < 0.05). In conclusion, in the absence of an efficient screening test, the diagnosis of MH/MUH can be assisted by the detection of the "isolated high office aSBP" phenotype, which can be measured in a single office visit. MHs/MUHs have increased aSBP relative to normotensives, further explaining the increased mortality of MH/MUH.