Association Between rs243866 Polymorphism of the MMP-2 Gene and Target Organ Damage in Patients with Uncontrolled Hypertension.

Background: Uncontrolled hypertension (UHT) is associated with an increased risk of target organ damage (TOD). Matrix metalloproteinase-2 (MMP-2) plays a role in vascular remodeling, and the rs243866 (-1575G/A) polymorphism has been implicated in cardiovascular diseases. Objective: This study aimed to evaluate the association between rs243866 and TOD in UHT patients. Methods: A cross-sectional study was conducted on 134 UHT patients at two hospitals in Vietnam. Genotyping of rs243866 was performed using PCR, and TOD was assessed via echocardiography (left ventricular hypertrophy - LVH), renal function tests (eGFR, albuminuria), and carotid ultrasound (carotid atherosclerosis). Results: The genotypic distribution was GG (79.9%), GA (18.6%), and AA (1.5%), with allele frequencies of 89.2% (G) and 10.8% (A). The A allele was associated with higher risks of LVH (OR=2.553, 95% CI: 1.052-6.196, p=0.035), CKD (OR=2.639, 95% CI: 0.986-7.066, p=0.048), and carotid atherosclerosis (OR=6.806, 95% CI: 2.203-21.024, p<0.001). These associations remained significant after adjusting for confounders. Conclusion: The rs243866 polymorphism of MMP-2 is independently associated with TOD in UHT, particularly LVH, CKD, and carotid atherosclerosis. Genetic screening for rs243866 may provide insights into risk stratification and personalized hypertension management.

Relationship of osteopontin, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, C-reactive protein and target organ damage in patients with essential hypertension

The relationship between resting pulse rate (PR) and the occurrence of hypertension and cardiovascular (CV) mortality has been described in the general population. Few studies have examined the relationship between ambulatory PR, ambulatory blood pressure (BP), and target organ damage (TOD) in patients with chronic kidney disease (CKD). A total of 1509 patients with CKD were recruited in our hospital. Ambulatory blood pressure monitoring (ABPM) over a 24-hours period was performed and referenced with clinical data in this cross-sectional study. TOD was measured by estimated glomerular filtration rate (eGFR), left ventricular hypertrophy (LVH), and carotid intima-media thickness (cIMT). Univariate and multivariate analyses were used to evaluate the relationship between PR, BP, and TOD. The percentage of male patients was 58.3% with a mean age of 44.6±16.2years. Nocturnal PR rather than 24-hours PR or daytime PR was an independent risk factor for clinical hypertension, 24-hours hypertension, BP dipper state, poor renal function, and LVH. In addition, the authors found that nighttime PR >74 beats/min (bpm) group was independently associated with clinical hypertension, 24-hours hypertension, day and night hypertension, nondipping BP, lower eGFR, and LVH when compared with nighttime PR <64bpm group. Furthermore, 1:1 propensity score matching between PR ≤74bpm group and PR >74bpm group was performed. Multivariate analyses indicated nighttime PR >74bpm remained independently associated with clinical hypertension, daytime and nighttime hypertension, and LVH. An increased nocturnal PR is associated with TOD, higher BP, and nondipping BP in patients with CKD.

BackgroundThe EPHES trial (Evaluation of influence of fixed dose combination Perindo-pril/amlodipine on target organ damage in patients with arterial HypErtension with or without iSchemic heart disease) compared the dynamics of target organ damage (TOD) in hypertensive patients with and without ischemic heart disease (IHD) treated with the fixed-dose combination (FDC) perindopril + amlodipine.MethodsThe analysis included 60 hypertensive patients (aged >30 years): 30 without IHD and 30 with IHD. At randomization, FDC was administered at a daily baseline dose of 5/5 mg with uptitration to 10/10 mg every two weeks. If target blood pressure (BP<140/90 mmHg) was not achieved after six weeks, indapamide 1.5 mg was added to the regimen. All patients underwent body mass index measurements, office and ambulatory BP measurements, pulse wave velocity (PWVe) and central systolic BP evaluation, augmentation index adjusted to heart rate 75 (Aix@75) evaluation, biochemical analysis, ECG, echocardiography with Doppler, ankle-brachial index measurement, and intima-media thickness measurement. The follow-up period was 12 months.ResultsTherapy based on FDC perindopril/amlodipine was effective in lowering BP (office, ambulatory, central) in both groups. We noted significant decrease in Aix@75 with the therapy in both groups, but ΔAix@75 was lesser in the group with IHD than the group without IHD. FDC provided significant improvement in PWVe and left ventricular diastolic function, and decrease in albuminuria, left ventricular hypertrophy (LVH), and left atrium size. ΔPWVe was significantly (P<0.005) less in patients without IHD than those with IHD (2.5±0.2 vs 4.4±0.5 m/s, respectively). In spite of almost equal LVH regression, the positive dynamics of ΔE/A and ΔE/E´ were more in patients with IHD than those without IHD (64.4% and 54.1% vs 39.8 and 23.2%, respectively; P<0.05 for both comparisons). Adverse reactions were in 2 (6.5%) patients without IHD and 3 (10%) with IHD (P=NS). In the group with IHD, we noted significant decrease in angina episode rate – from 2.5±0.4 to 1.2±0.2 (P<0.01) per week.ConclusionThus, treatment based on FDC was effective in decreasing BP and TOD regression in both patients with and without IHD. However, the dynamics of changes in TOD were different between the two groups, which should be taken into consideration during management of patients with and without IHD.

This paper aims to investigate whether there is a relationship between left atrial diameter (LAD) and target organ damage (TOD) in patients with type 2 diabetes mellitus (DM). Two-hundred-and-eleven patients with type 2 DM were recruited. Data on left ventricular mass index (LVMI), diabetic retinopathy, carotid intima–media thickness/carotid plaque, micro-albuminuria, and serum creatinine levels were collected to determine whether TOD occurred in patients with type 2 DM. Age, body mass index, waist-hip ratio, a history of DM, Framingham Score, and 10-year risk were used to assess cardiovascular disease risk. Patients were divided into four groups: zero TOD (group I, n = 50), one TOD marker (group II, n = 76), two TOD markers (group III, n = 51), and at least three TOD markers (group IV, n = 34). Using multivariate regression analyses, age, body mass index, waist-hip ratio, a history of DM, Framingham Score, and 10-year risk were significantly associated with LAD. LAD was associated with an increased number of markers for TOD. Univariate analyses demonstrated significant relationships between LAD and TOD in the context of serum creatinine and urinary albumin creatinine ratio (r = 0.292, p < 0.001), creatinine (r = 0.346, p < 0.001), carotid intima–media thickness (r = 0.128, p = 0.032), and LVMI (r = 0.399, p < 0.001). Multivariate regression analyses also determined that LVMI and creatinine were independent predictors of LAD enlargement. LAD may be associated with cardiovascular disease risk. LAD enlargement could be an effective indicator of TOD, particularly renal impairment and left ventricular hypertrophy. Screening for LAD may offer a new and rapid approach for evaluating the severity of DM.

Aim: to evaluate the efficiency of starting fixed-dose combination therapy with eprosartan and hydrochlorothiazide on the clinical and subclinical parameters of target organ damage in patients with hypertensive disease (HD) irrespective of baseline blood pressure (BP) and cardiovascular risk. Subjects and methods. The study consisted of two parallel substudies. Substudy 1 that screened 3536 workers from industrial enterprises identified 395 (13%) hypertensive patients. Among them, there were 50 (12,7%) untreated patients with HD who had three-component target organ damages: left ventricular hypertrophy, hypertensive nephropathy, peripheral artery lesion. Sixty (15,2%) untreated patients with Stage 1 HD without clinical signs of organ changes were recorded among the same cohort in Substudy 2. In both substudies, Group 1 received a fixed-dose combination of eprosartan mesylate 600 mg once daily and hydrochlorothiazide 12,5 once daily regardless of baseline BP at the onset of the study. Group 2 had monotherapy with enalapril and/or its combination with hydrochlorothiazide depending on the degree of BP elevation and the group of a cardiovascular risk. Results. Starting fixed-dose combination antihypertensive therapy (eprosartan + hydrochlorothiazide) irrespective of baseline BP and cardiovascular risk versus monotherapy with enalapril and/or its free combination with hydrochlorothiazide, which was used in terms of BP level and cardiovascular risk ensured a more significant regression of both clinical and subclinical target organ damages during 6-month therapy according to the changes in left ventricular mass (LVM), LVM index, and tissue inhibitor of type 1 matrix metalloproteinases, microalbuminuria and glomerular filtration rate, intima-media complex thickness during carotid Doppler ultrasound study, and pulse wave velocity in different segments, as evidenced by volumetric sphygmoplethysmography. Conclusions. The use of a fixed-dose combination of eprosartan and hydrochlorothiazide in untreated patients of able-bodied age regardless of baseline BP and cardiovascular risk ensures the regression of target organ damages and the prevention of their development in the absence of organ changes.

BACKGROUND: It is unclear about the association between vitamin D level and target organ damage in elderly patients with type 2 diabetes in China. Aim of this study was to investigate the relationship between vitamin D level and target organ damage in elderly patients with type 2 diabetes of Chinese population. &#x0D; &#x0D; METHODS: A retrospective study was performed on 254 elderly patients with type 2 diabetes (148 males and 106 females). According to assay of 25-hydroxy vitamin D [25(OH)D], the participants were divided into a deficiency group (n=129), an insufficiency group (n=77) and a sufficiency group (n=48). The clinical indicators of target organ damages among these groups were analyzed, and multivariate logistic regression analysis was performed to predict the target organ damage. &#x0D; &#x0D; RESULTS: Approximately 81.1% of patients were the low level of 25(OH)D with mean 25(OH)D below 30ng/ml. When compared with those in the sufficiency group, the level of left ventricular absolute mass index (LVMI), the morning urine albumin/uric creatinine ratio (ACR) and carotid intimal medial thickness (cIMT) increased significantly and creatinine clearance rate (CcR) decreased significantly in the deficiency group (P&amp;lt;0.05). The level of ACR and cIMT in the insufficiency group also increased significantly (P&amp;lt;0.05). There was a higher proportion in kidney, brain, artery and total target organ damage in the deficiency group or insufficiency group than those in the sufficiency group (P&amp;lt;0.05). Logistic regression analysis showed that low-level 25(OH)D&amp;nbsp; (&amp;lt; 30ng/ml) was independently associated with total target organ damage in patients with elderly type 2 diabetes (OR = 3.58; 95%CI: 1.60-8.02,P =0.002)&#x0D; &#x0D; CONCLUSIONS: A condition of hypovitaminosis D is commonly present in Chinese patients with elderly type 2 diabetes. The low level of 25(OH)D may contribute to aggravate target organ damage of elderly type 2 diabetes.

BackgroundHypertension is a major risk factor for cardiovascular mortality, as it acts through its effects on target organs, such as the heart and kidneys. Hyperuricemia increases cardiovascular risk in patients with hypertension.ObjectiveTo assess the relationship between serum uric acid and target organ damage (left ventricular hypertrophy and microalbuminuria) in untreated patients with essential hypertension.Patients and methods: A cross-sectional study was carried out in 130 (85 females, 45 males) newly diagnosed, untreated patients with essential hypertension. Sixty-five healthy age- and sex-matched non-hypertensive individuals served as controls for comparison. Left ventricular hypertrophy was evaluated by cardiac ultrasound scan, and microalbuminuria was assessed in an early morning midstream urine sample by immunoturbidimetry. Blood samples were collected for assessing uric acid levels.ResultsMean serum uric acid was significantly higher among the patients with hypertension (379.7±109.2 μmol/L) than in the controls (296.9±89.8 μmol/L; P<0.001), and the prevalence of hyperuricemia was 46.9% among the hypertensive patients and 16.9% among the controls (P<0.001). Among the hypertensive patients, microalbuminuria was present in 54.1% of those with hyperuricemia and in 24.6% of those with normal uric acid levels (P=0.001). Similarly, left ventricular hypertrophy was more common in the hypertensive patients with hyperuricemia (70.5% versus 42.0%, respectively; P=0.001). There was a significant linear relationship between mean uric acid levels and the number of target organ damage (none versus one versus two: P=0.012).ConclusionThese results indicate that serum uric acid is associated with target organ damage in patients with hypertension, even at the time of diagnosis; thus, it is a reliable marker of cardiovascular damage in our patient population.

Fibulin-1, an extracellular matrix protein, is a potential biomarker for cardiovascular disease, but its association with target organ damage (TOD) in high-risk patients remains unclear. We prospectively analysed 330 patients undergoing invasive coronary angiography (ICA) (mean age, 64.7 ± 10.7 years; female, 37.9%). Blood samples obtained just before invasive coronary angiography (ICA) were stored for subsequent measurement of fibulin-1 levels using an enzyme-linked immunosorbent assay. During index admission, eight TOD parameters (obstructive coronary artery disease, impaired kidney function, increased arterial stiffness, left ventricular hypertrophy, left ventricular diastolic dysfunction and arterial occlusive disease of peripheral arteries) were assessed. Long-term clinical follow-up data on major adverse cardiovascular events (MACE) were also collected. Fibulin-1 levels were significantly higher in patients with multiple TOD compared to those without (506 ± 229 vs. 354 ± 148 mcg/mL; p < .001). Serum fibulin-1 levels increased proportionally with the number of TODs (p < .001). Multivariable analyses identified that each 100 mcg/mL increase in serum fibulin-1 level was significantly associated with an increased risk of multiple TOD, even after adjustment for potential confounders (odds ratio: 1.29-1.45; p < .05). Similarly, each 100 mcg/mL increase in serum fibulin-1 level was associated with a 29% higher incidence of MACE (95% confidence interval, 1.14-1.46; p < .001). Fibulin-1 is strongly associated with the extent of TOD and may serve as a useful biomarker for risk stratification in high-risk patients.

Objectives: To determine the association between morning hypertension and target organ damage (TOD) in patients with chronic kidney disease (CKD) and hypertension.Methods: In this cross-sectional study, 447 patients with CKD and hypertension from two centers were enrolled. Ambulatory blood pressure monitoring was conducted in all patients. Linear regression and logistic regression analysis were used to determine the association between morning hypertension and TOD in patients with CKD and hypertension, including assessments of estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), urine protein/creatinine ratio (UPCR), and left ventricular hypertrophy (LVH).Results: Overall, 194 (43.4%) participants had morning hypertension. Morning hypertension was strongly correlated with LVH [odds ratio (OR), 2.14; 95% confidence interval (CI), 1.3–3.51; p < 0.01], lower level of eGFR (β = −0.51; 95%CI, −0.95–−0.08; p < 0.05), higher LVMI (β = 0.06; 95%CI, 0.04–0.08, p < 0.001), and UPCR (β = 0.22; 95%CI, 0.06–0.38, p < 0.01), independent of nocturnal hypertension and elevated morning blood pressure surge. As a continuous variable, both morning systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found to be associated with LVH and higher level of UPCR and LVMI (p < 0.05), whereas only morning SBP was negatively correlated with eGFR (p < 0.01).Conclusion: Morning hypertension was strongly correlated with cardiac damage and impaired kidney function in CKD patients with hypertension, independent of nocturnal hypertension and morning surge in blood pressure. Morning hypertension in CKD patients warrants further attention.

BackgroundIt is unclear whether short-term blood pressure variability (BPV) is associated with target organ damage in patients with non-dialysis chronic kidney disease (CKD).MethodsA cross-sectional, single-center study was conducted among 3442 non-dialysis CKD patients hospitalized in the department of Nephrology of the Fifth Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2022 and collected the demographic, laboratory, clinic blood pressure, ambulatory blood pressure data, and short-term BPV assessed by the weighted standard deviation (wSD) derived from ambulatory blood pressure monitoring (ABPM). Multivariate logistic analyses were used to evaluate the independent effects between short-term BPV and subclinical target organ damage, including left ventricular hypertrophy (LVH), abnormal carotid intima-media thickness (CIMT), low estimated glomerular filtration rate (eGFR), and albuminuria.ResultsThe average age of the participants was 47.53 ± 14.06 years and 56% of participants were male. The baseline eGFR was 69 mL/min/1.73 m2. Based on the tertile distribution of wSD according to equal numbers, patients were divided into three categories with T1(< 9.66 mmHg), T2(9.66–12.23 mmHg), and T3(> 12.23 mmHg) of SBPV; T1(< 8.17 mmHg), T2(8.17–9.93 mmHg), and T3(> 9.93 mmHg) of DBPV. The participants with the higher wSD group had a higher prevalence of target organ damage than their counterparts (P-trend < 0.05). An increasing trend in short-term variability was present with advancing CKD stages (P-trend < 0.001). Multivariate logistic analyses results showed that the odds ratio (OR) of SBP wSD was (1.07 [1.03,1.11], P < 0.001) for LVH, (1.04 [1.01,1.07, P = 0.029) for abnormal CIMT, (1.05 [1.02,1.08], P = 0.002) for low eGFR, and (1.06 [1.02,1.09], P = 0.002) for albuminuria; The OR of DBP wSD was (1.07 [1.02,1.12], P = 0.005) for LVH, (1.05 [1.01,1.09], P = 0.028) for abnormal CIMT, (1.05 [1.01,1.09], P = 0.022) for low eGFR, and (1.05 [1.01,1.10], P = 0.025) for albuminuria when adjusted for confounding factors and mean BP.ConclusionsIn conclusion, short-term BPV is associated with target organ damage, and irresponsible of average blood pressure levels, in Chinese non-dialysis CKD participants.

Background:Essential hypertension is a multifactorial disease, which is affected by genetic and environmental factors, and can cause diseases such as cerebrovascular disease, heart failure, coronary heart disease, and chronic renal failure. High salt intake is a risk factor for hypertension, stroke, and cardiovascular disease. Blood pressure variability (BPV) is a reliable independent predictor of cardiovascular events and death. At present, there are few studies about the correlation among high salt intake, BPV, and target organ damage (TOD) in patients with hypertension.Objective:The purpose of this study is to compare 24-hour urine sodium excretion, BPV, carotid intima–media thickness, left ventricular mass index, and serum creatinine or endogenous creatinine clearance rate. To clarify the relationship between high salt load and BPV and TOD in patients with hypertension.This study is a cross-sectional study. It will recruit 600 patients with essential hypertension in the outpatient and inpatient department of cardiovascular medicine of Chengdu Fifth People's Hospital. Researchers will obtain blood and urine samples with the patient's informed consent. In addition, we will measure patient's blood pressure and target organ-related information.Trial registry:The study protocol was approved by the Chengdu Fifth People's Hospital. Written informed consent will be obtained from all the participants. The trial was registered in the Chinese Clinical trial registry, ChiCTR2000029243. This trial will provide for the correlation among high salt intake, BPV, and TOD in patients with essential hypertension.

Objective: The metabolic syndrome (MS) and arterial hypertension (AH) is associated with a 2-fold increase in cardiovascular diseases and outcomes. Although many patients may not have symptoms at first. The aims of this study were to assess the target organ damage in patients with MS and AH first degree. Design and method: The study included 60 untreated patients with abdominal obesity, AH first degree and dyslipidemia and 20 healthy participants (control group). 56% of patients had newly diagnosed hypertension. Office blood pressure (BP), 24-hour ambulatory blood pressure monitoring), blood sampling and measurements of fasting and postprandial blood glucose, lipids levels, endothelial vasoactive mediators (NO metabolite, endothelin-1, thromboxane B2 and 6-keto-prostaglandin F1alpha), carotid ultrasonography and echocardiography had performed at baseline. Results: The majority of patients with MS and AH 1 degree had metabolic abnormalities: 13% the increased fasting glucose level and 40% increased postprandial glucose level. The overall prevalence rates of circadian BP pattern were as follows: 15% riser; 50% no dipper and only 35% with normal BP falling. The levels of vasoconstrictive mediators were significantly higher in comparison with control group (figure). Part of patients had lesions of carotid arteries: carotid artery plaques were presented in 30% and increase intima medial thickness in 35% of patients. 40% of patients with MS and AH 1 degree had left ventricular hypertrophy and 85% diastolic dysfunction.Conclusions: The results showed high prevalence of target organ damage in untreated patients with MS and AH first degree. The majority of patients had impaired nocturnal blood pressure decline associates to higher incidence on stroke, chronic kidney disease, and other cardiovascular diseases.

Hyperhomocysteinemia (HHcy) is recognized as a risk factor for cardiovascular disease. However, the prevalence of HHcy and its role in association with target organ damage in patients with chronickidney disease (CKD) are not well understood. This cross-sectional study included 1042 CKD patients who were admitted to our hospital. Patients were divided into two groups: hyperhomocysteinemia and normohomocysteinemia. Multivariable linear regression analyses were used to evaluate the association between plasma homocysteine and renal/cardiovascular parameters. The prevalence of HHcy in patients with CKD was 52.78%, and the prevalence in CKD stage 1, stage 2, stage 3, stage 4 and stage 5 patients was 10.73%, 29.22%, 58.71%, 75.23% and 83.75%, respectively. Patients with HHcy had higher incidences of renal damage, left ventricular hypertrophy, left ventricular diastolic dysfunction and abnormal carotid intima-media thickness compared with patients with normohomocysteinemia (p < 0.05), while multivariable linear regression analyses showed plasma homocysteine was only associated with the estimated glomerular filtration rate (eGFR). eGFR, uric acid, albumin, gender, hemoglobin and calcium×phosphate were associated with levels of plasma homocysteine in these CKD patients. The prevalence of HHcy in Chinese patients with CKD was high, and serum homocysteine levels were associated with impaired renal function in these patients.

The aim of this study was to determine the proportion of isolated clinical hypertension (ICH) in newly diagnosed hypertensive patients, and to compare the incidence of target organ damage (TOD) in ICH and sustained hypertension patients. Participants. In a multi‐centre study involving 14 primary care centres in Girona, Spain, 140 researchers recruited 214 newly diagnosed hypertensive patients 15–75 years of age, without history of cardiovascular events. Period of study. 2004–6. Method. Self‐blood pressure monitoring (SBPM) and ambulatory blood pressure monitoring (ABPM). Evaluation. Anamnesis including blood pressure, physical examination and analysis (creatinine, albumin/creatinine index), electrocardiogram (left ventricular hypertrophy) and retinography (fundus damage). Results. In 129 (60.3%) subjects with sustained hypertension and 85 (39.7%) with ICH, no significant differences were found relative to gender, age, body mass index or blood pressure (155/90 vs 154/90 mmHg, respectively). Cholesterol levels were significant differences between both groups (5.97 mmol/l in sustained hypertension vs 5.64 mmol/l in ICH, p = 0.029). The proportion of ICH was approximately 40%. TOD incidence in sustained hypertensives was similar to that of ICH patients.