Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment.

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.

Potential effects of the hydrostatic pressure gradient on hyperemic and nonhyperemic pressure ratios.

When measuring hyperemic and nonhyperemic pressure ratios with traditional sensor-tipped wires, the inevitable hydrostatic pressure gradient (HPG) may influence treatment decisions. This study aimed to simulate and analyze the effect of a hydrostatic pressure gradient on different indices of functional lesion severity. A hypothetical Pd-Pa height difference and subsequent hydrostatic pressure gradient based on previous literature was applied to the pressure measurements from the CONTRAST study. The effect on three indices of functional lesion severity (FFR, Pd/Pa, and dPR) was assessed and possible reclassifications in functional significance by the different indices were analyzed. In 602 pressure tracings, simulated hydrostatic pressure gradients led to an absolute change in Pd of 3.18 ± 1.30 mmHg, resulting in an overall increase in FFR, Pd/Pa, and dPR of 0.02 ± 0.04 for all indices (P = 0.69). Reclassification due to the hydrostatic pressure gradient when using dichotomous cutoff values occurred in 13.4, 22.3, and 20.6% for FFR, Pd/Pa, and dPR, respectively. The effect of hydrostatic pressure gradient correction differed among the coronary arteries and was most pronounced in the left anterior descending. When considering the gray zone for the different functional indices, the hydrostatic pressure gradient resulted in reclassification in only one patient out of the complete patient population (1/602; 0.17%). The hydrostatic pressure gradient can influence functional lesion assessment when using dichotomous cutoff values. When taking the gray zone into account, its effect is limited.NEW & NOTEWORTHY This study systematically simulated the effect of hydrostatic pressure gradients (HPG) on real-world hyperemic and nonhyperemic pressure ratios, showing correction for HPG leads to reclassification in functional significance from 13.4 to 22.3% for different functional indices. This was most pronounced in nonhyperemic pressure ratios. A new pressure guidewire (Wirecath) is unaffected by HPG. The ongoing PW-COMPARE study (NCT04802681) prospectively analyzes the magnitude and importance of HPG by simultaneous FFR measurements.

Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies.

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Low mechano-energetic efficiency is associated with future left ventricular systolic dysfunction in hypertensives.

AIMS: In a hypertensive population with optimal blood pressure control with a long-term follow-up, we aimed at analysing possible predictors of left ventricular (LV) ejection fraction (LVEF) reduction, including indexed mechano-energetic efficiency (MEEi), a well-recognized echo-derived parameter of LV performance. METHODS AND RESULTS: The study population included 5673 hypertensive patients from the Campania Salute Network with a long-term follow-up, normal baseline LVEF (≥50%), and no prevalent cardiovascular (CV) disease. Patients developing LVEF impairment (LVEF < 50% or a reduction of at least 10 percentage points compared with baseline) were compared with patients with persistently normal LVEF. Optimal blood pressure control was achieved in about 80% of patients. Patients who experienced LVEF reduction were 2.41% during a long-term follow-up (mean duration 5.6 ± 3.9 years). At baseline, they were older (59.46 ± 11.58 vs. 53.40 ± 11.41, P < 0.0001) and showed higher LV mass index (53.3 ± 12.83 vs. 47.56 ± 9.58, P < 0.0001), left atrial (LA) volume index (14.4 ± 4.2 vs. 13.1 ± 2.8, P < 0.0001) and carotid intima-media thickness (1.99 ± 0.86 vs. 1.61 ± 0.73, P < 0.0001), lower MEEi (0.32 ± 0.08 vs. 0.34 ± 0.07, P = 0.037), and higher prevalence of CV events during follow-up (13.9% vs. 3%, P < 0.0001) compared with patients with persistently normal LVEF. A logistic regression analysis, performed after running univariate analyses and selecting parameters significantly associated with LVEF reduction, showed that having a CV event [odds ratio (OR) 7.57, P < 0.0001], being in the lowest MEEi quartile (OR 2.43, P = 0.003), and having a larger LA volume index (OR 1.08, P = 0.028) were all parameters independently associated with the development of LV systolic dysfunction. A further logistic regression model, performed by excluding patients experiencing CV events, demonstrated that the lowest MEEi quartile was independently associated with the evolution towards LVEF reduction (OR 2.35, P = 0.004), despite significant impact of LA volume index (OR 1.08, P = 0.023) and antiplatelet therapy (OR 1.89, P < 0.01). Receiver operating characteristic curves showed that the model including MEEi had higher accuracy than the model without MEEi in predicting LVEF reduction (areas under the curve 0.68 vs. 0.63, P = 0.046). CONCLUSIONS: Lower values of MEEi at baseline identify hypertensive patients more liable to develop LVEF reduction. In hypertensive setting, MEEi evaluation improves risk stratification for development of LV systolic dysfunction during long-term follow-up.

The intergated approach to the management of arterial hypertension: The Campania Salute Network.

The second half of the last century was characterized by intense research in the field of arterial hypertension and related therapies. These studies showed that the management of arterial hypertension requires a robust coordination with close integration of the "health care systems" and "health care professionals." In 1998, the healthcare organization named "Campania Salute Network" was set up at the Federico II University, Naples, Italy. The Campania Salute Network involves 23 outpatient hypertensive clinics distributed in different community hospitals of the Regione Campania's area, 60 randomly selected general practitioners uniformly distributed in the same area, and the Hypertension Clinic of the Federico II University (coordinating center). Through this network, clinical data collected at each visit are shared (via text messages or e-mails) with peripheral units (general practitioners and community hospital outpatient hypertensive clinics). The coordinating centre works in cooperation with the peripheral units in the treatment and follow-up of all hypertensive patients (i.e. assessing hypertension mediated organ damage and associated diseases). Information about patients are shared through on-line access to the remote web-based database. The integrated approach to the mamangement of hyperetension determined a better control of blood pressure, that was associated with a reduction of hypertension mediated organ damage and decreased incidence of fatal or non-fatal cardiovascular events. Furthermore, this innovative approach improved the adherence and the persistence to the initial pharmacologic treatment. Campania Salute Network is also a powerful tool for the clinical and translational research with more 15,000 hypertensive patients followed for more than 15 years. This database allowed, in prospetic, large scale studies, to identify the hemodiminamic and metabolic determinants of hypertension mediated organ damage and major cardiovascular events. The experience of Campania Salute Netwiork indicates that the creation of large databases from real life experiences becomes an indispensable condition also for artificial intelligence which, in the near future, thanks to scientific knowledge, the availability of particularly advanced hardware and software, will also be able to transform the management of arterial hypertension.

Atrial Dilatation Development in Hypertensive Treated Patients: The Campania-Salute Network.

BACKGROUND: Left atrial (LA) dilatation is associated with unfavorable outcome in hypertension. However, there are few data on clinical, demographic, and echocardiographic findings correlated with LA dilatation development. METHODS: From the Campania-Salute Network registry, we identified 5,375 hypertensive patients (52±11 years, 38% women) in normal sinus rhythm, with normal LA diameter (parasternal short-axis <24.0 in women and <25.4mm/m in men), with normal left ventricular (LV) ejection fraction, and with at least 12 months of echocardiographic follow-up. We included in the clinic evaluation type of antihypertensive drugs. RESULTS: Follow-up duration was of 70±48 months. During follow-up, 647 patients (12%) showed LA dilatation. Patients with incident LA dilatation were older, most likely to be women, more obese, more diabetics, with lower Modification of Diet in Renal Disease, higher total cholesterol, lower uric acid, higher pulse pressure, lower heart rate, higher LV mass, concentric geometry and lower E/A ratio at mitral level, longer E deceleration time, and higher intima-media carotid thickness. They take more drugs, and follow-up was longer (overall P < 0.05). In the Cox analysis, age, female gender, obesity, higher LV mass, LA diameter at baseline, and longer E deceleration time were determinants of LA dilatation. Furthermore, the use of diuretics protected against LA dilatation. CONCLUSIONS: Our data identify a risk profile for LA dilatation, characterized by older age, female sex, obesity, higher LV mass, and worse diastolic function. In this subgroup of patients, the use of diuretics seems to protect against LA dilatation.