Galectin-3: A Link between Myocardial and Arterial Stiffening in Patients with Acute Decompensated Heart Failure?

Abstract Background: Heart failure is accompanied by abnormalities in ventricular-vascular interaction due to increased myocardial and arterial stiffness. Galectin-3 is a recently discovered biomarker that plays an important role in myocardial and vascular fibrosis and heart failure progression. Objectives: The aim of this study was to determine whether galectin-3 is correlated with arterial stiffening markers and impaired ventricular-arterial coupling in decompensated heart failure patients. Methods: A total of 79 inpatients with acute decompensated heart failure were evaluated. Serum galectin-3 was determined at baseline, and during admission, transthoracic echocardiography and measurements of vascular indices by Doppler ultrasonography were performed. Results: Elevated pulse wave velocity and low arterial carotid distensibility are associated with heart failure in patients with preserved ejection fraction (p = 0.04, p = 0.009). Pulse wave velocity, carotid distensibility and Young’s modulus did not correlate with serum galectin-3 levels. Conversely, raised galectin-3 levels correlated with an increased ventricular-arterial coupling ratio (Ea/Elv) p = 0.047, OR = 1.9, 95% CI (1.0‑3.6). Increased galectin-3 levels were associated with lower rates of left ventricular pressure rise in early systole (dp/dt) (p=0.018) and raised pulmonary artery pressure (p = 0.046). High galectin-3 levels (p = 0.038, HR = 3.07) and arterial pulmonary pressure (p = 0.007, HR = 1.06) were found to be independent risk factors for all-cause mortality and readmissions. Conclusions: This study showed no significant correlation between serum galectin-3 levels and arterial stiffening markers. Instead, high galectin-3 levels predicted impaired ventricular-arterial coupling. Galectin-3 may be predictive of raised pulmonary artery pressures. Elevated galectin-3 levels correlate with severe systolic dysfunction and together with pulmonary hypertension are independent markers of outcome.

Influence of age, risk factors, and cardiovascular and renal disease on arterial stiffness: clinical applications.

Age is the main clinical determinant of large artery stiffness. Central arteries stiffen progressively with age, whereas peripheral muscular arteries change little with age. A number of clinical studies have analyzed the effects of age on aortic stiffness. Increase of central artery stiffness with age is responsible for earlier wave reflections and changes in pressure wave contours. The stiffening of aorta and other central arteries is a potential risk factor for increased cardiovascular morbidity and mortality. Arterial stiffening with aging is accompanied by an elevation in systolic blood pressure (BP) and pulse pressure (PP). Although arterial stiffening with age is a common situation, it has now been confirmed that older subjects with increased arterial stiffness and elevated PP have higher cardiovascular morbidity and mortality. Increase in aortic stiffness with age occurs gradually and continuously, similarly for men and women. Cross-sectional studies have shown that aortic and carotid stiffness (evaluated by the pulse wave velocity) increase with age by approximately 10% to 15% during a period of 10 years. Women always have 5% to 10% lower stiffness than men of the same age. Although large artery stiffness increases with age independently of the presence of cardiovascular risk factors or other associated conditions, the extent of this increase may depend on several environmental or genetic factors. Hypertension may increase arterial stiffness, especially in older subjects. Among other cardiovascular risk factors, diabetes type 1 and 2 accelerates arterial stiffness, whereas the role of dyslipidemia and tobacco smoking is unclear. Arterial stiffness is also present in several cardiovascular and renal diseases. Patients with heart failure, end stage renal disease, and those with atherosclerotic lesions often develop central artery stiffness. Decreased carotid distensibility, increased arterial thickness, and presence of calcifications and plaques often coexist in the same subject. However, relationships between these three alterations of the arterial wall remain to be explored.

Improved prediction of coronary heart disease with markers of atherosclerosis and of inflammation in older adults?

Background: Several markers of atherosclerosis and of inflammation have been shown to predict coronary heart disease (CHD) individually. However, the utility of markers of atherosclerosis and of inflammation on prediction of CHD over traditional risk factors has not been well established, especially in the elderly. Methods: We studied 2202 men and women, aged 70-79, without baseline cardiovascular disease over 6-year follow-up to assess the risk of incident CHD associated with baseline noninvasive measures of atherosclerosis (ankle-arm index [AAI], aortic pulse wave velocity [aPWV]) and inflammatory markers (interleukin-6 [IL-6], C-reactive protein [CRP], tumor necrosis factor-a [TNF-a]). CHD events were studied as either nonfatal myocardial infarction or coronary death ("hard" events), and "hard" events plus hospitalization for angina, or the need for coronary-revascularization procedures (total CHD events). Results: During the 6-year follow-up, 283 participants had CHD events (including 136 "hard" events). IL-6, TNF-a and AAI independently predicted CHD events above Framingham Risk Score (FRS) with hazard ratios [HR] for the highest as compared with the lowest quartile for IL-6 of 1.95 (95%CI: 1.38-2.75, p for trend <0.001), TNF-a of 1.45 (95%CI: 1.04-2.02, p for trend 0.03), of 1.66 (95%CI: 1.19-2.31) for AAI 0.9, as compared to AAI 1.01-1.30. CRP and aPWV were not independently associated with CHD events. Results were similar for "hard" CHD events. Addition of IL-6 and AAI to traditional cardiovascular risk factors yielded the greatest improvement in the prediction of CHD; C-index for "hard"/total CHD events increased from 0.62/0.62 for traditional risk factors to 0.64/0.64 for IL-6 addition, 0.65/0.63 for AAI, and 0.66/0.64 for IL-6 combined with AAI. Being in the highest quartile of IL-6 combined with an AAI 0.90 or >1.40 yielded an HR of 2.51 (1.50-4.19) and 4.55 (1.65-12.50) above FRS, respectively. With use of CHD risk categories, risk prediction at 5 years was more accurate in models that included IL-6, AAI or both, with 8.0, 8.3 and 12.1% correctly reclassified, respectively. Conclusions: Among older adults, markers of atherosclerosis and of inflammation, particularly IL-6 and AAI, are independently associated with CHD. However, these markers only modestly improve cardiovascular risk prediction beyond traditional risk factors.

The Effect of Valsartan versus Non-RAAS Treatment on Autoregulation of Cerebral Blood Flow.

Background: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). Methods: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO(2) pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. Results: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (-0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (-0.23 ± 0.06 vs. -0.08 ± 0.07%, p = 0.07). Conclusions: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes.

AIM: Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased cardiovascular risk due to an accelerated atherosclerotic process. The present study aimed to compare skin microvascular function, pulse wave velocity (PWV), and a variety of hemostatic markers of endothelium injury [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and the soluble form of thrombomodulin (s-TM)] in patients with NIDDM. METHODS: 54 patients with NIDDM and 38 sex- and age-matched controls were studied. 27 diabetics had no overt micro- and/or macrovascular complications, while the remainder had either or both. The forearm skin blood flow was assessed by laser-Doppler imaging, which allowed the measurement of the response to iontophoretically applied acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation), as well as the reactive hyperemia triggered by the transient occlusion of the circulation. RESULTS: Both endothelial and non-endothelial reactivity were significantly blunted in diabetics, regardless of the presence or the absence of vascular complications. Plasma vWF, TFPI and s-TM levels were significantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were significantly increased in the two groups of diabetics versus controls. CONCLUSION: In NIDDM, both endothelium-dependent and -independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to reflect a hypercoagulable state.

Markers of atherosclerosis and of inflammation for prediction of coronary heart disease in older adults

BACKGROUND: Several markers of atherosclerosis and of inflammation have been shown to predict coronary heart disease (CHD) individually. However, the utility of markers of atherosclerosis and of inflammation on prediction of CHD over traditional risk factors has not been well established, especially in the elderly. METHODS: We studied 2202 men and women, aged 70-79, without baseline cardiovascular disease over 6-year follow-up to assess the risk of incident CHD associated with baseline noninvasive measures of atherosclerosis (ankle-arm index [AAI], aortic pulse wave velocity [aPWV]) and inflammatory markers (interleukin-6 [IL-6], C-reactive protein [CRP], tumor necrosis factor-a [TNF-a]). CHD events were studied as either nonfatal myocardial infarction or coronary death ("hard" events), and "hard" events plus hospitalization for angina, or the need for coronary-revascularization procedures (total CHD events). RESULTS: During the 6-year follow-up, 283 participants had CHD events (including 136 "hard" events). IL-6, TNF-a and AAI independently predicted CHD events above Framingham Risk Score (FRS) with hazard ratios [HR] for the highest as compared with the lowest quartile for IL-6 of 1.95 (95%CI: 1.38-2.75, p for trend<0.001), TNF-a of 1.45 (95%CI: 1.04-2.02, p for trend 0.03), of 1.66 (95%CI: 1.19-2.31) for AAI £0.9, as compared to AAI 1.01-1.30. CRP and aPWV were not independently associated with CHD events. Results were similar for "hard" CHD events. Addition of IL-6 and AAI to traditional cardiovascular risk factors yielded the greatest improvement in the prediction of CHD; C-index for "hard"/total CHD events increased from 0.62/0.62 for traditional risk factors to 0.64/0.64 for IL-6 addition, 0.65/0.63 for AAI, and 0.66/0.64 for IL-6 combined with AAI. Being in the highest quartile of IL-6 combined with an AAI £ 0.90 or >1.40 yielded an HR of 2.51 (1.50-4.19) and 4.55 (1.65-12.50) above FRS, respectively. With use of CHD risk categories, risk prediction at 5 years was more accurate in models that included IL-6, AAI or both, with 8.0, 8.3 and 12.1% correctly reclassified respectively. CONCLUSIONS: Among older adults, markers of atherosclerosis and of inflammation, particularly IL-6 and AAI, are independently associated with CHD. However, these markers only modestly improve cardiovascular risk prediction beyond traditional risk factors. Acknowledgments: This study was supported by Contracts NO1-AG-6-2101, NO1-AG-6- 2103, and NO1-AG-6-2106 of the National Institute on Aging. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.

Non-invasive and non-occlusive blood pressure estimation via a chest sensor.

The clinical demand for a device to monitor Blood Pressure (BP) in ambulatory scenarios with minimal use of inflation cuffs is increasing. Based on the so-called Pulse Wave Velocity (PWV) principle, this paper introduces and evaluates a novel concept of BP monitor that can be fully integrated within a chest sensor. After a preliminary calibration, the sensor provides non-occlusive beat-by-beat estimations of Mean Arterial Pressure (MAP) by measuring the Pulse Transit Time (PTT) of arterial pressure pulses travelling from the ascending aorta towards the subcutaneous vasculature of the chest. In a cohort of 15 healthy male subjects, a total of 462 simultaneous readings consisting of reference MAP and chest PTT were acquired. Each subject was recorded at three different days: D, D+3 and D+14. Overall, the implemented protocol induced MAP values to range from 80 ± 6 mmHg in baseline, to 107 ± 9 mmHg during isometric handgrip maneuvers. Agreement between reference and chest-sensor MAP values was tested by using intraclass correlation coefficient (ICC = 0.78) and Bland-Altman analysis (mean error = 0.7 mmHg, standard deviation = 5.1 mmHg). The cumulative percentage of MAP values provided by the chest sensor falling within a range of ±5 mmHg compared to reference MAP readings was of 70%, within ±10 mmHg was of 91%, and within ±15mmHg was of 98%. These results point at the fact that the chest sensor complies with the British Hypertension Society (BHS) requirements of Grade A BP monitors, when applied to MAP readings. Grade A performance was maintained even two weeks after having performed the initial subject-dependent calibration. In conclusion, this paper introduces a sensor and a calibration strategy to perform MAP measurements at the chest. The encouraging performance of the presented technique paves the way towards an ambulatory-compliant, continuous and non-occlusive BP monitoring system.

Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults.

Although both inflammatory and atherosclerosis markers have been associated with coronary heart disease (CHD) risk, data directly comparing their predictive value are limited. The authors compared the value of 2 atherosclerosis markers (ankle-arm index (AAI) and aortic pulse wave velocity (aPWV)) and 3 inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)) in predicting CHD events. Among 2,191 adults aged 70-79 years at baseline (1997-1998) from the Health, Aging, and Body Composition Study cohort, the authors examined adjudicated incident myocardial infarction or CHD death ("hard" events) and "hard" events plus hospitalization for angina or coronary revascularization (total CHD events). During 8 years of follow-up between 1997-1998 and June 2007, 351 participants developed total CHD events (197 "hard" events). IL-6 (highest quartile vs. lowest: hazard ratio = 1.82, 95% confidence interval: 1.33, 2.49; P-trend < 0.001) and AAI (AAI </= 0.9 vs. AAI 1.01-1.30: hazard ratio = 1.57, 95% confidence interval: 1.14, 2.18) predicted CHD events above traditional risk factors and modestly improved global measures of predictive accuracy. CRP, TNF-alpha, and aPWV had weaker associations. IL-6 and AAI accurately reclassified 6.6% and 3.3% of participants, respectively (P's </= 0.05). Results were similar for "hard" CHD, with higher reclassification rates for AAI. IL-6 and AAI are associated with future CHD events beyond traditional risk factors and modestly improve risk prediction in older adults.

Citrate- vs. acetate-based dialysate in bicarbonate haemodialysis: consequences on haemodynamics, coagulation, acid-base status, and electrolytes.

BACKGROUND: A concentrate for bicarbonate haemodialysis acidified with citrate instead of acetate has been marketed in recent years. The small amount of citrate used (one-fifth of the concentration adopted in regional anticoagulation) protects against intradialyser clotting while minimally affecting the calcium concentration. The aim of this study was to compare the impact of citrate- and acetate-based dialysates on systemic haemodynamics, coagulation, acid-base status, calcium balance and dialysis efficiency. METHODS: In 25 patients who underwent a total of 375 dialysis sessions, an acetate dialysate (A) was compared with a citrate dialysate with (C+) or without (C) calcium supplementation (0.25 mmol/L) in a randomised single-blind cross-over study. Systemic haemodynamics were evaluated using pulse-wave analysis. Coagulation, acid-base status, calcium balance and dialysis efficiency were assessed using standard biochemical markers. RESULTS: Patients receiving the citrate dialysate had significantly lower systolic blood pressure (BP) (-4.3 mmHg, p < 0.01) and peripheral resistances (PR) (-51 dyne.sec.cm-5, p < 0.001) while stroke volume was not increased. In hypertensive patients there was a substantial reduction in BP (-7.8 mmHg, p < 0.01). With the C+ dialysate the BP gap was less pronounced but the reduction in PR was even greater (-226 dyne.sec.cm-5, p < 0.001). Analyses of the fluctuations in PR and of subjective tolerance suggested improved haemodynamic stability with the citrate dialysate. Furthermore, an increase in pre-dialysis bicarbonate and a decrease in pre-dialysis BUN, post-dialysis phosphate and ionised calcium were noted. Systemic coagulation activation was not influenced by citrate. CONCLUSION: The positive impact on dialysis efficiency, acid-base status and haemodynamics, as well as the subjective tolerance, together indicate that citrate dialysate can significantly contribute to improving haemodialysis in selected patients.

Haemodynamic consequences of changing bicarbonate and calcium concentrations in haemodialysis fluids.

BACKGROUND: In a previous study we demonstrated that mild metabolic alkalosis resulting from standard bicarbonate haemodialysis induces hypotension. In this study, we have further investigated the changes in systemic haemodynamics induced by bicarbonate and calcium, using non-invasive procedures. METHODS: In a randomized controlled trial with a single-blind, crossover design, we sequentially changed the dialysate bicarbonate and calcium concentrations (between 26 and 35 mmol/l for bicarbonate and either 1.25 or 1.50 mmol/l for calcium). Twenty-one patients were enrolled for a total of 756 dialysis sessions. Systemic haemodynamics was evaluated using pulse wave analysers. Bioimpedance and BNP were used to compare the fluid status pattern. RESULTS: The haemodynamic parameters and the pre-dialysis BNP using either a high calcium or bicarbonate concentration were as follows: systolic blood pressure (+5.6 and -4.7 mmHg; P < 0.05 for both), stroke volume (+12.3 and +5.2 ml; P < 0.05 and ns), peripheral resistances (-190 and -171 dyne s cm(-5); P < 0.05 for both), central augmentation index (+1.1% and -2.9%; ns and P < 0.05) and BNP (-5 and -170 ng/l; ns and P < 0.05). The need of staff intervention was similar in all modalities. CONCLUSIONS: Both high bicarbonate and calcium concentrations in the dialysate improve the haemodynamic pattern during dialysis. Bicarbonate reduces arterial stiffness and ameliorates the heart tolerance for volume overload in the interdialytic phase, whereas calcium directly increases stroke volume. The slight hypotensive effect of alkalaemia should motivate a probative reduction of bicarbonate concentration in dialysis fluid for haemodynamic reasons, only in the event of failure of classical tools to prevent intradialytic hypotension.

The Macrocirculation and Microcirculation of Hypertension.

Changes in vascular structure that accompany hypertension may contribute to hypertensive end-organ damage. Both the macrovascular and microvascular levels should be considered, as interactions between them are believed to be critically important. Regarding the macrocirculation, the article first reviews basic concepts of vascular biomechanics, such as arterial compliance, arterial distensibility, and stress-strain relationships of arterial wall material, and then reviews how hypertension affects the properties of conduit arteries, particularly examining evidence that it accelerates the progressive stiffening that normally occurs with advancing age. High arterial stiffness may increase central systolic and pulse pressure by two different mechanisms: 1) Abnormally high pulse wave velocity may cause pressure waves reflected in the periphery to reach the central aorta in systole, thus augmenting systolic pressure; 2) In the elderly, the interaction of the forward pressure wave with high arterial stiffness is mostly responsible for abnormally high pulse pressure. At the microvascular level, hypertensive disease is characterized by inward eutrophic or hypertrophic arteriolar remodeling and capillary rarefaction. These abnormalities may depend in part on the abnormal transmission of highly pulsatile blood pressure into microvascular networks, especially in highly perfused organs with low vascular resistance, such as the kidney, heart, and brain, where it contributes to hypertensive end-organ damage.

Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies.

BACKGROUND: Assisted reproductive technology (ART) involves the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Environmental influences during the embryonic and fetal development influence the individual's susceptibility to cardiovascular disease, raising concerns about the potential consequences of ART on the long-term health of the offspring. METHODS AND RESULTS: We assessed systemic (flow-mediated dilation of the brachial artery, pulse-wave velocity, and carotid intima-media thickness) and pulmonary (pulmonary artery pressure at high altitude by Doppler echocardiography) vascular function in 65 healthy children born after ART and 57 control children. Flow-mediated dilation of the brachial artery was 25% smaller in ART than in control children (6.7±1.6% versus 8.6±1.7%; P<0.0001), whereas endothelium-independent vasodilation was similar in the 2 groups. Carotid-femoral pulse-wave velocity was significantly (P<0.001) faster and carotid intima-media thickness was significantly (P<0.0001) greater in children conceived by ART than in control children. The systolic pulmonary artery pressure at high altitude (3450 m) was 30% higher (P<0.001) in ART than in control children. Vascular function was normal in children conceived naturally during hormonal stimulation of ovulation and in siblings of ART children who were conceived naturally. CONCLUSIONS: Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors but to the ART procedure itself. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00837642.

Systemic vascular dysfunction in patients with chronic mountain sickness.

ABSTRACT BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem characterized by exaggerated hypoxemia and erythrocytosis. In more advanced stages, these patients often present functional and structural changes of the pulmonary circulation, but there is little information on the systemic circulation. In patients suffering from diseases associated with chronic hypoxemia at low altitude, systemic vascular function is altered. We hypothesized that patients with CMS display systemic vascular dysfunction that may predispose them to increased systemic cardiovascular morbidity. METHODS: To test this hypothesis, we assessed systemic endothelial function (by flow- mediated dilation, FMD), arterial stiffness and carotid intima-media thickness and arterial oxygenation (SaO(2)) in 23 patients with CMS without additional classical cardiovascular risk factors and 27 age-matched healthy mountain dwellers born and permanently living at 3600 m. For some analyses subjects were classified according to baseline SaO(2) quartiles; FMD of the highest quartile subgroup (SaO(2) ≥90%) was used as reference value for post-hoc comparisons. RESULTS: Patients with CMS displayed marked systemic vascular dysfunction, as evidenced by impaired FMD (4.6±1.2 vs. 7.6±1.9%, CMS vs. controls, P<0.0001), greater pulse wave velocity (10.6±2.1 vs. 8.4±1.0 m/s, P<0.001) and carotid intima-media thickness (690±120 vs. 570±110 μm, P=0.001). A positive relationship existed between SaO(2) and FMD (r=0.62, P<0.0001). Oxygen inhalation improved (P<0.001), but did not normalize FMD in patients with CMS; whereas it normalized FMD in hypoxemic controls (SaO(2) <90%) and had no detectable effect in normoxemic (SaO(2) ≥90%) control subjects. CONCLUSIONS: Patients with CMS display marked systemic vascular dysfunction. Structural and functional alterations contribute to this problem that may predispose these patients to premature cardiovascular disease. Clinical Trials Gov Registration # NCT01182792.

Site-specific coupling between vascular wall thickness and function: an observational MRI study of vessel wall thickening and stiffening in hypertension.

OBJECTIVES: The objective of this study was to evaluate associations between aortic pulse wave velocity (PWV) and aortic and carotid vessel wall thickness (VWT) using cardiovascular magnetic resonance imaging (MRI) in patients with hypertension as compared with healthy adult volunteers. MATERIALS AND METHODS: Local medical ethics approval was obtained and the participants gave informed consent. Fifteen patients with hypertension (5 men and 10 women; mean [SD] age, 49 [14] years) and 15 age- and sex-matched healthy volunteers were prospectively included and compared. All participants underwent MRI examination for measuring aortic and carotid VWT and aortic PWV with well-validated MRI techniques at 1.5- and 3-T MRI systems: PWV was assessed from velocity-encoded MRI and VWT was assessed by using dual-inversion black-blood gradient-echo imaging techniques. Paired t tests were used for testing differences between the volunteers and the patients and Pearson correlation (r) and univariable and multivariable stepwise linear regression analyses were used to test associations between aortic and carotid arterial wall thickness and stiffness. RESULTS: Mean values for aortic PWV and aortic and carotid VWT (indexed for body surface area [BSA]) were all significantly higher in patients with hypertension as compared with the healthy volunteers (ie, aortic PWV, 7.0 ± 1.4 m/s vs 5.7 ± 1.3 m/s; aortic VWT/BSA, 0.12 ± 0.03 mL/m vs 0.10 ± 0.03 mL/m; carotid VWT/BSA, 0.04 ± 0.01 mL/m vs 0.03 ± 0.01 mL/m; all P < 0.01). Aortic PWV was highly correlated with aortic VWT/BSA (r = 0.76 and P = 0.002 in the patients vs r = 0.63 and P = 0.02 in the volunteers), and in the patients, aortic PWV was moderately correlated with carotid VWT/BSA (r = 0.50; P = 0.04). In the volunteers, correlation between aortic PWV and carotid VWT/BSA was not significant (r = 0.40; P = 0.13). In addition, aortic VWT/BSA was significantly correlated with carotid VWT/BSA, in both the patients (r = 0.60; P = 0.005) and volunteers (r = 0.57; P = 0.007). CONCLUSIONS: In the patients with hypertension and the healthy volunteers, the aortic PWV is associated more strongly with aortic wall thickness than with carotid wall thickness, reflecting site-specific coupling between vascular wall thickness and function.

Overlap Between Common Genetic Polymorphisms Underpinning Kidney Traits and Cardiovascular Disease Phenotypes: The CKDGen Consortium.

BACKGROUND: Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits. STUDY DESIGN: We conducted 2 targeted analyses. First, we examined whether known single-nucleotide polymorphisms (SNPs) underpinning kidney traits were associated with a series of vascular phenotypes. Additionally, we tested whether vascular SNPs were associated with markers of kidney damage. Significance was set to 1.5×10(-4) (0.05/325 tests). SETTING & PARTICIPANTS: Vascular outcomes were analyzed in participants from the AortaGen (20,634), CARDIoGRAM (86,995), CHARGE Eye (15,358), CHARGE IMT (31,181), ICBP (69,395), and NeuroCHARGE (12,385) consortia. Tests for kidney outcomes were conducted in up to 67,093 participants from the CKDGen consortium. PREDICTOR: We used 19 kidney SNPs and 64 vascular SNPs. OUTCOMES & MEASUREMENTS: Vascular outcomes tested were blood pressure, coronary artery disease, carotid intima-media thickness, pulse wave velocity, retinal venular caliber, and brain white matter lesions. Kidney outcomes were estimated glomerular filtration rate and albuminuria. RESULTS: In general, we found that kidney disease variants were not associated with vascular phenotypes (127 of 133 tests were nonsignificant). The one exception was rs653178 near SH2B3 (SH2B adaptor protein 3), which showed direction-consistent association with systolic (P = 9.3 ×10(-10)) and diastolic (P = 1.6 ×10(-14)) blood pressure and coronary artery disease (P = 2.2 ×10(-6)), all previously reported. Similarly, the 64 SNPs associated with vascular phenotypes were not associated with kidney phenotypes (187 of 192 tests were nonsignificant), with the exception of 2 high-correlated SNPs at the SH2B3 locus (P = 1.06 ×10(-07) and P = 7.05 ×10(-08)). LIMITATIONS: The combined effect size of the SNPs for kidney and vascular outcomes may be too low to detect shared genetic associations. CONCLUSIONS: Overall, although we confirmed one locus (SH2B3) as associated with both kidney and cardiovascular disease, our primary findings suggest that there is little overlap between kidney and cardiovascular disease risk variants in the overall population. The reciprocal risks of kidney and cardiovascular disease may not be genetically mediated, but rather a function of the disease milieu itself.