Increased erythrocyte sodium-lithium countertransport activity in essential hypertension is due to an increased affinity for extracellular sodium

1. Sodium-lithium countertransport activity in a standard assay, its sodium affinity constant and maximum velocity were measured in erythrocytes from normal subjects and from essential hypertensive patients with and without a family history of hypertension. 2. In normal subjects the sodium concentration used in the standard assay was similar to the sodium affinity constant so that the activity measured in this assay was less than the maximum velocity. 3. In patients with essential hypertension and a positive family history, 33% had a sodium-lithium countertransport activity greater than the upper limit of the normal control range (0.4 mmol of Li+ h-1 l-1 of cells). 4. The reason for the raised sodium-lithium countertransport activity was an increased sodium affinity (lower sodium affinity constant) at the outside ion-binding site. 5. Of the patients with essential hypertension and a positive family history but sodium-lithium countertransport activity within the normal range in the standard assay, 30% also had a low sodium affinity constant. 6. A low sodium affinity constant at the outside site of the sodium-lithium countertransporter may be a more specific indicator for a group of patients with inherited hypertension than the standard sodium-lithium countertransport activity assay.     

Abnormal thiol group modulation of sodium-lithium countertransport and membrane fluidity is associated with a disturbed relationship between serum triacylglycerols and membrane function in type II diabetes

In essential hypertension and diabetic nephropathy, sodium-lithium countertransport (Na-Li CT) is an inherited marker, subject to metabolic influences, of cardiovascular risk. Studies in Type II diabetes, taking clinical phenotypes as their starting point, are conflicting. We sought to identify Na-Li CT kinetic abnormalities in Type II diabetes, and only subsequently to seek relationships with clinical variables. Na-Li CT kinetics, membrane fluidity and their modulation by thiol proteins were measured in erythrocytes from 38 patients with Type II diabetes and in 16 normal control subjects. In untreated erythrocytes, Na-Li CT kinetics were similar. Thiol protein alkylation with N-ethylmaleimide generally caused both V(max) and K(m) to fall, but caused K(m) to rise in erythrocytes from 13 out of 38 diabetic subjects, whose native K(m) was low (P=0. 0013 compared with control). V(max) and serum triacylglycerol levels were related in normal controls (r(s)=0.54, P=0.038) and in diabetic subjects whose K(m) fell after N-ethylmaleimide (n=25, r(s)=0.62, P=0.001). Where the K(m) rose after N-ethylmaleimide, V(max) and triacylglycerol levels were not related (n=13, r(s)=-0.39, P=0.183) and membrane fluidity did not increase after N-ethylmaleimide. However, these subgroups were indistinguishable in terms of blood pressure, albuminuria, glycaemia or lipid profiles. Thus abnormalities in the regulation of Na-Li CT and membrane fluidity by key thiol proteins, resembling those seen in essential hypertension and diabetic nephropathy, were apparent in one-third of subjects with Type II diabetes. Membrane abnormalities may indicate a common pathological mechanism. The prognostic significance of Na-Li CT kinetic abnormalities in Type II diabetes must now be confirmed.     

Prevalence of peripheral arterial disease in high‐risk patients using ankle‐brachial index in general practice: a cross‐sectional study

Aims: The deleterious nature of peripheral arterial disease (PAD) is compounded by a status of underdiagnosed and undertreated disease. We evaluated the prevalence and predictive factors of PAD in high‐risk patients using the ankle‐brachial index (ABI). Methods: The ABI was measured by general practitioners in France (May 2005–February 2006) in 5679 adults aged 55 years or older and considered at high risk. The primary outcome was prevalence of PAD (ABI strictly below 0.90). Results: In all, 21.3% patients had signs or symptoms suggestive of PAD, 42.1% had previous history of atherothrombotic disease and 36.6% had two or more cardiovascular risk factors. Prevalence of PAD was 27.8% overall, ranging from 10.4% in patients with cardiovascular risk factors only to approximately 38% in each other subgroup. Prevalence differed depending on the localization of atherothrombotic events: it was 57.1–75.0% in patients with past history of symptomatic PAD; 24.6–31.1% in those who had experienced cerebrovascular and/or coronary events. Regarding the classical cardiovascular risk factors, PAD was more frequent when smoking and hypercholesterolemia history were reported. PAD prevalence was also higher in patients with history of abdominal aortic aneurysm, renal hypertension or atherothrombotic event. Intermittent claudication, lack of one pulse in the lower limbs, smoking, diabetes and renovascular hypertension were the main factors predictive of low ABI. Conclusions: Given the elevated prevalence of PAD in high‐risk patients and easiness of diagnosis using ABI in primary care, undoubtedly better awareness would help preserve individual cardiovascular health and achieve public health goals.     

Diabetic nephropathy. Future avenue.

Diabetes mellitus has become the leading cause of ESRF in the United States. Patients with diabetic nephropathy suffer high cardiovascular morbidity and mortality. Because only 40% of diabetic patients eventually develop diabetic kidney disease, it may be possible to devise primary prevention measures targeted at the subset of patients at risk. Recently, a predisposition to hypertension, a family history of diabetic nephropathy, and a family history of CVD disease each have been associated independently with the development of diabetic renal complication in IDDM. Risk factors for macrovascular damage, including raised arterial BP, dyslipidemia, and insulin resistance, can be detected early in the course of progression to diabetic nephropathy. These risk indicators recently have been shown to be already present at the stage of normoalbuminuria in those patients who eventually will progress to microalbuminuria. Treatment of established renal disease can only delay the onset of ESRF, and lowering of microalbuminuria has been shown to retard the onset of persistent proteinuria. However, no study to date has demonstrated prevention of renal disease in these patients. The ultimate aim should, therefore, be the prevention of the transition from normoalbuminuria to microalbuminuria in individuals who are at higher risk of diabetic renal disease and CVD.     

心血管疾病患者合并抑郁的临床调查

目的调查常见心血管疾病住院患者合并抑郁的发病率及相关因素。方法用汉密尔顿抑郁量表(HAMD)对619例常见心血管疾病患者进行抑郁评分;用单因素及多元逐步回归分析其影响因素。结果①619例常见心血管疾病住院患者中合并抑郁196例,发病率为31.7%;冠心病、原发性高血压、高血压合并冠心病、慢性充血性心力衰竭(CHF)合并抑郁的发病率分别为29.1%、24.3%、37.7%、41.8%。②常见心血管疾病住院患者合并抑郁的发生与性别、家庭成员人数、负性生活事件、住院次数、病情程度及病程有关。结论常见心血管疾病住院患者易合并抑郁,其中CHF组发病率最高;女性、家庭成员少、有负性生活事件、住院次数多和病程长的患者更易发生。     

Impact of genetic defects on atherosclerosis in patients suspected of familial hypercholesterolaemia

BACKGROUND: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, we assessed whether patients with mutations of low-density lipoprotein (LDL) receptor and apolipoprotein B genes related to familial hypercholesterolaemia (FH) have a different degree of atherosclerosis than those without such mutations. METHOD: In our lipid clinics, 273 patients were selected on the basis of a severe hypercholesterolaemia (cholesterol above 95th percentile) and a family history of early cardiovascular disease. By molecular genetic test, 122 patients were classified as FH. Atherosclerosis was evaluated by the ultrasonographic measurement of intima-media thickness (IMT) in the carotid and femoral arteries. RESULT: Despite the fact that non-FH individuals had a higher prevalence of obesity, hypertension, diabetes and hypertriglyceridaemia, FH individuals had significantly greater carotid and femoral IMT than non-FH patients: difference between carotid and femoral IMT, respectively, 0.19 mm (95% CI, 0.08-0.29; P < 0.001) and 0.20 mm (95% CI, 0.09-0.35; P = 0.001), respectively. These differences remained statistically significant after adjustment for the various risk factors as well as in sub-analysis restricted to the patients with LDL-cholesterol between 240 and 300 mg dL-1 (range with similar distribution in the two groups). When classified according to the severity of their mutations, FH individuals with null LDL receptor allele tended to have thicker carotid IMT than FH individuals carrying the LDL receptor-defective allele. CONCLUSION: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher degree of atherosclerosis. This suggests that molecular genetic identification of FH may be helpful to evaluate better the coronary heart disease risk in these patients.     

The Detection of Renovascular Hypertension: A Study of 490 Patients by Renal Angiography

Four hundred and ninety patients with hypertension were studiedto determine those clinical characteristics or simple investigationsthat predict the presence of operable renal artery stenosison renal angiography. One hundred and fifty two of the 490 patientswere below the age of 40, had a good response to treatment,a normal physical examination, normal renal function, and normalintravenous pyelogram. Only one of the 152 patients had an operablerenal artery lesion. Of the remaining 338 patients, 168 hadnormal angiograms, 50 had surgically correctable renal arterystenosis, 75 had renal artery narrowing of less than 70 percent and 45 patients had significant parenchymal renal disease.Abnormal renal angiograms were found significantly (p < 0.05)more often in patients with poor control of blood pressure,impaired renal function or a history of antipyretic analgesicabuse. Our experience in hypertensive patients suggests that renalarteriography is unlikely to provide useful information in patientsunder 40 years old, but may well demonstrate a remediable abnormalityin older patients with poor control of hypertension associatedwith a history of antipyretic analgesic abuse and/or impairedrenal function.     

Urine Dipstick as a Screening Test for Serum Creatinine Elevation in Emergency Department Patients with Severe Hypertension

OBJECTIVE: Patients presenting to the emergency department (ED) with severe hypertension require assessment for acute end-organ damage. Serum creatinine (SCr) measurement is routinely recommended to detect renal dysfunction. The authors assessed the utility of the urine dipstick test in screening for acute SCr elevation in this population. METHODS: The authors performed a prospective study of adult ED patients with diastolic blood pressures > or = 115 mm Hg that persisted for > or = 30 minutes or necessitated emergent treatment. Excluded were menstruating and pregnant women and patients with urinary infection, trauma, or dialysis dependence. Patients reporting a history of renal disease were excluded if the SCr was abnormal and no baseline value was available. Each subject had an SCr and urine dipstick test. The authors examined the performance of the dipstick in identifying an elevated SCr, defined as SCr > 1.2 mg/dL or > 25% above baseline. RESULTS: Of 143 patients, 42 had SCr > 1.2 mg/dL. Eighteen reported prior renal disease but had an SCr that was normal or < or = 25% above baseline. The remaining 24 subjects comprised the elevated SCr group. The presence of either proteinuria or hematuria on dipstick identified these patients with 100% sensitivity and 29.7% specificity. Specificity rose to 42.4% without loss of sensitivity when an abnormal dipstick was defined as hematuria or > or = 1+ proteinuria. CONCLUSIONS: The urine dipstick may be an effective screening test for SCr elevation in patients with severe hypertension. A restrictive definition of an abnormal dipstick would identify all patients with elevated SCr and substantially reduce the number of SCr assays necessary.     

Association of serum lipoprotein(a) concentration with other cardiovascular risk factors in a Chinese population.

The association between serum Lp(a) concentration, a risk factor for atherothrombotic disease, and other cardiovascular risk factors such as smoking, alcohol intake, hypertension, obesity, and indices of glycemic control is examined in a cohort of 313 elderly Chinese subjects (M = 160, mean age +/- SD = 68 +/- 11 year; F = 153, mean age +/- SD = 73 +/- 11). Although associations existed for the above risk factors and other serum lipid levels, there was no association with serum Lp(a) concentration in the overall population. Men with Lp(a) greater than or equal to 30 mg/dl had a higher mean age and blood pressure. A higher percentage of subjects with Lp(a) greater than or equal to 30 mg/dl had a family history of stroke, although the total number of those with a family history was too small to reach statistical significance. The lack of association with known modifiable cardiovascular risk factors is compatible with the conclusion that Lp(a) concentration is primarily under genetic control and therefore unlikely to be a modifiable risk factor.     

Abdominal sonographic study of autosomal dominant polycystic kidney disease

PURPOSE: The purpose of this study was to determine whether kidney size in patients who have autosomal dominant polycystic kidney disease (ADPKD) is related to renal function, hypertension, or extrarenal manifestations of the disease and to sonographically evaluate the abdominal manifestations of ADPKD. METHODS: Between 1994 and 1998, 400 individuals from 85 families with a history of ADPKD were examined. There were 213 persons with ADPKD and 187 unaffected family members; there were 182 males and 218 females, 1-82 years old (mean, 39.3 years). We obtained a complete medical history, performed a physical examination, measured the arterial blood pressure and serum creatinine levels, and performed abdominal sonography on each subject. The sonographic features that were studied were renal length and the presence and number of cysts on the kidneys, liver, and pancreas. RESULTS: There was a relationship between kidney size and age (p < 0.05), kidney size and renal function (p < 0.001), and kidney size and hypertension (p < 0.001). The overall prevalence of hepatic cysts in patients with ADPKD was 67%, and the prevalence increased with age. The presence of hepatic cysts was related to the severity of renal disease. Females had more severe polycystic liver disease, and massive polycystic liver disease (ie, hepatomegaly with innumerable cysts) was seen only in females. The prevalence of pancreatic cysts in the 187 persons in whom the pancreas was well evaluated sonographically was 5%. CONCLUSIONS: Kidney size in patients with ADPKD is related to renal function, hypertension, and extrarenal involvement and can be used to predict the outcome of the disease. Hepatic cysts are very common in patients with ADPKD and are related to age and renal function; pancreatic cysts are infrequent in these patients.     

广东家族性原发性高血压遗传方式分析:多中心调查

背景:原发性高血压的发病机制与遗传有关且多数人认为其遗传方式为多基因遗传.作者在广东多年的遗传病临床实习带教中,观察到许多高血压家系特征与常染色体显性遗传极为相似.目的:探讨家族性高血压的遗传方式.方法:采用家系分析、Smith无偏差校正法、多基因分析法对广东药学院4个附属医院以及广东地区8所县医院的高血压有关专科就诊的具有家族史、24～88岁的高血压患者及家系进行遗传方式分析.结果与结论:调查的215个核心家系的1326人中,总同胞数为914人,男483人,女431人,其中患者442例,男230例,女212例.亲属的患病率为442/914=0.483 6,与常染色体显性遗传的理论值0.5接近(P>0 05).男性患病率为230/442=0.520 4,女性患病率为212/442=0.479 6,符合常染色体显性遗传男女发病机会均等这一理论假设.215个核心家系中的211个核心家系其高血压的遗传方式支持常染色体显性遗传.由多基因分析可知本研究中家族性原发性高血压家系的观察值为63.63,与常染色体显性遗传的期望值65.79最接近,并与多基因遗传的期望值11.47相差甚远.因此,多基因分析结果表明,家族性高血压遗传方式支持常染色体显性遗传.调查结果提示家族性原发性高血压有单基因的常染色体显性遗传方式,又有单基因的常染色体隐性遗传方式.提示有家族史的原发性高血压患者可为高危人群,注意预测亲属的发病风险,对预防原发性高血压有一定的指导意义.美键词:家族性高血压;多基因检验;Smith无偏差校正法;常染色体显性遗传     

Mild hypertension in children

Essential hypertension (EHT) is found in 0.1 to 1% of Japanese school children. HT remains one of the major risk factors for the development of atherosclerosis and subsequent cardiovascular disease. EHT during childhood is usually mild, however, associated with end-organ damage such as left ventricular hypertrophy. In addition, it develops into adult hypertension. EHT is often seen in obese children. Furthermore, low birth weight has been reported to be closely associated with future EHT. Obese children are increasing and birth weight has a tendency of decreasing in Japan, it is, therefore, important to establish proper life-style from childhood throughout life.     

Impact of genetic defects on coronary atherosclerosis in patients suspected of having familial hypercholesterolaemia

BACKGROUND: In the present study we assessed whether the presence of genetic mutations typical of familial hypercholesterolaemia (FH) was associated with greater atherosclerosis in the coronary vessels in patients with severe hypercholesterolaemia and a family history of early cardiovascular disease. MATERIALS AND METHODS: Two hundred and thirty-five patients selected for having severe hypercholesterolaemia and a family history of cardiovascular disease were classified as FH (57 men and 38 women) or non-FH (84 men and 56 women) according to a genetic analysis of the LDL-R or ApoB genes. Coronary atherosclerosis was evaluated by performing a thoracic CT scan and exercise stress testing. RESULTS: Familial hypercholesterolaemia individuals had a significantly higher prevalence of coronary calcification than the non-FH patients from among both the men (OR = 3.90; 95% CI 1.86-8.19; P < 0.001) and the women (OR = 2.34; 95% CI 1.01-5.48; P = 0.05). In exercise stress testing, ECG abnormalities suggestive of cardiac ischaemia were found with a higher prevalence in the FH patients than the non-FH patients from among both the men (OR 6.15; 95% CI 2.16-17.5; P < 0.001) and the women (OR 4.76; 95% CI 0.91-24.6; P = 0.06). All differences were statistically significant after adjusting for age and cholesterol and for most classical risk factors that differed between the FH and non-FH groups. CONCLUSION: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher prevalence of coronary artery calcifications and a positive exercise stress test. These results suggest that despite a similar phenotype, patients carrying mutations suggestive of FH may have a greater cardiovascular risk than patients without these mutations.     

Effects of Baseline Left Ventricular Hypertrophy and Decreased Renal Function on Cardiovascular and Renal Outcomes in Patients with Fabry Disease Treated with Agalsidase Alfa: A Fabry Outcome Survey Study

PurposeThe initiation of enzyme-replacement therapy prior to the occurrence of substantial and irreversible organ damage in patients with Fabry disease is of critical importance. The Fabry Outcome Survey is an international disease registry of patients with a confirmed diagnosis of Fabry disease. In this study, data from the Fabry Outcome Survey were used for the assessment of the risks for cardiovascular and renal events in patients who received agalsidase alfa treatment.MethodsEligible patients were males and females aged ≥18 years with Fabry disease treated with agalsidase alfa. Cardiovascular events included myocardial infarction, left ventricular hypertrophy (LVH), heart failure, arrhythmia, conduction abnormality, and cardiac surgery. Renal events included dialysis, transplantation, and renal failure. Kaplan–Meier curves and log-rank tests were used for comparing event-free probabilities and time to first cardiovascular or renal event, from agalsidase alfa initiation to a maximum of 120 months, in patients with LVH versus normal left ventricular mass index (LVMI; ≤50 g/m^2.7 in males and ≤48 g/m^2.7 in females) at treatment initiation (baseline), and in patients with a low estimated glomerular filtration rate (eGFR; <90 mL/min/1.73 m²) versus normal eGFR at baseline. Multivariate Cox regression analysis was used for examining the association between key study variables and the risks for cardiovascular and renal events.FindingsAmong the 560 patients (269 males; 291 females) with available LVMI data, 306 (55%) had LVH and 254 (45%) had normal LVMI at baseline. The risk for a cardiovascular event was higher in the subgroup with LVH versus normal LVMI at baseline (hazard ratio [HR] = 1.57; 95% CI, 1.21–2.05; P < 0.001), but the risk for a renal event was similar between the 2 subgroups (HR = 1.90; 95% CI, 0.94–3.85; P = 0.074). Among the 1093 patients (551 males; 542 females) with available eGFR data, 433 (40%) had a low eGFR and 660 (60%) had a normal eGFR at baseline. The subgroup with a low eGFR at baseline had a significantly higher risk for a cardiovascular event (HR = 1.33; 95% CI, 1.04–1.70; P = 0.021) or a renal event (HR = 5.88; 95% CI, 2.73–12.68; P < 0.001) compared with patients with a normal eGFR at baseline.ImplicationsIn the present study, the presence of LVH and/or reduced renal function at agalsidase alfa initiation was associated with a significantly higher risk for a cardiovascular or renal event, indicating that cardiovascular and renal pathologies in Fabry disease may be inter-related. Early initiation of agalsidase alfa treatment prior to the onset of severe organ damage may improve outcomes. ClinicalTrials.gov identifier: NCT03289065.     

Plasma Renin in Hypertensive Patients: Significance in Relation to Clinical and Other Biochemical Features

Presenting features of 221 hypertensive patients were examinedin relation to plasma renin. One hundred and seventy-six patientshad essential hypertension, of these 47 had high plasma reninactivity (PRA), 80 had normal PRA and 49 low PRA. When the groupswith high and low PRA were compared with age and sex matchedpatients with normal PRA there was no difference with respectto clinical, radiological, electrocardio graphic and biochemicalcharacteristics. Twenty-five patients had radiological evidenceof unilateral renal or renovascular disease and twenty patientshad accelerated hypertension with advanced fundal changes: boththese groups had more severe hypertension, a higher plasma reninand evidence of greater cardiovascular morbidity than patientswith essential hypertension. Morbidity was equally high in patientswith accelerated hypertension whether PRA was high or normal.There is therefore no evidence to support the view that reninis an important factor in assessing risk in hypertension. If,on the other hand, specially referred patients with renovascularand accelerated hypertension are pooled with other hypertensivepatients, a spurious association between renin and cardiovascularmorbidity will be created.     

Sudden Death as a Presenting Symptom of Hypertrophic Cardiomyopathy: Treatment with an Implantable Cardioverter Defibrillator

Aborted sudden death as the presenting manifestation of hypertrophic Cardiomyopathy in a 14-year-old child is reported. Documented ventricular fibrillation was the cause of cardiac arrest. No ventricular arrhythmia was induced during programmed electrical stimulation. An implantable cardioverter-defibrillator was indicated. As the patient had a family history of myocardial disease, he had undergone a cardiovascular evaluation 4 years before the major event, and was found normal. It is suggested that normal physical examination, ECG, echocardiogram should not rule out the diagnosis of hypertrophic Cardiomyopathy when a family history is present. Left ventricular hypertrophy may develop during childhood in patients with hypertrophic Cardiomyopathy.     

肾小球疾病患者颈动脉粥样硬化的危险因素分析

目的 探讨肾小球疾病患者颈动脉粥样硬化(AS)的危险因素.方法 选择251例有肾内血管病变(IAL)患者(病变组)并随机选择与之年龄、血压和肾小球滤过率(eGFR)相匹配无IAL的肾小球疾病患者129例(无病变组),检测2组颈动脉内中膜厚度(IMT);并比较有、无AS患者临床、实验室检查和肾病理特点.结果 ①AS检出率:病变组38.2%高于无病变组20.2%;年龄≥40岁AS检出率51.3%高于＜40岁13.1%(均P＜0.05).②AS患者年龄、BMI、空腹血糖(FBG)、吸烟、高血压程度、已知高血压时间和高血压家族史、肾小球疾病病程、IAL、肾脏病变程度均高或长于无AS患者,eGFR低于无AS患者(均P＜0.05).回归分析示:IAL和年龄是颈AS的独立危险因素(OR=1.826,1.129;P=0.001,0.003).结论 IAL是肾小球疾病患者颈AS的独立危险因素.控制血糖、血压、体重,戒烟及延缓肾脏病进展对减轻或预防肾小球疾病患者IAL和AS有重要意义.     

Minor abnormalities of renal function: a situation requiring integrated management of cardiovascular risk

Changes in renal function related with essential hypertension are associated with an elevated cardiovascular morbidity and mortality. Indices of altered renal function (e.g. microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. The Framingham Heart Study documented the relevance of proteinuria for cardiovascular prognosis in the community. The Intervention as a Goal in Hypertension Treatment (INSIGHT) Study assessed the role of proteinuria as a very powerful risk factor. It has also been shown that microalbuminuria along with primary hypertension poses a high risk for cardiovascular diseases. Recent data indicate that even minor derangements of renal function are associated with the clustering of cardiovascular risk factors observed in metabolic syndrome, that promote progression of atherosclerosis. All these parameters should be routinely evaluated in clinical practice, and considered in any stratification of cardiovascular risk in hypertensive patients. The high prevalence of chronic kidney disease in the general and in the hypertensive populations implies the need for an integrative therapeutic approach to fully protect renal and cardiovascular systems simultaneously.