Chronic kidney disease, all-cause mortality and cardiovascular mortality among Chinese patients with established cardiovascular disease.

AIM: This study was conducted to investigate the role of chronic kidney disease (CKD) in 1-year all cause mortality and cardiovascular mortality among Chinese patients who were at least 50 years old and had a history of coronary artery disease (CAD), stroke, or peripheral vascular disease (PAD), or with two or more cardiovascular risks. METHODS: Of 3,732 hospitalized patients enrolled, 3,423 patients (91.7%) with complete data were eligible for 1-year follow-up. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2). RESULTS: 1,166 (34.1%) were diagnosed with CKD. Most cases were unrecognized. Patients having an eGFR of <30 mL/min/1.73 m(2) were less likely to be prescribed beta-blockers, statins, or aspirin (all p<0.001). A powerful relationship was observed between the severity of renal dysfunction and all causes of death or cardiovascular death. Adjusted for other covariates, the hazard ratio (HR) for all causes of death and for cardiovascular death among patients with an eGFR of 30-45 mL/min/1.73 m(2) was 1.70 (95% CI, 1.18-2.45) and 1.85 (95% CI, 1.12-3.01) as compared with 2.93 (95% CI, 1.96-4.38) and 3.47 (95% CI, 1.91-6.31) for patients with an eGFR of <30 mL/min/1.73 m(2). CONCLUSIONS: One third of Chinese patients at high risk for atherosclerotic events were diagnosed with CKD. Most of these cases were unrecognized and undertreated. An eGFR of <45 mL/min/1.73 m(2) was an independent predictor of all causes of death and of cardiovascular death.

Prevalence of and risk factors for peripheral arterial disease among Chinese hypertensive patients with and without known cardiovascular disease.

INTRODUCTION: Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis.The present study was to estimate the prevalence of and risk factors for PAD in Chinese hypertensive patients with and without known cardiovascular disease (CVD) which consisted of coronary heart disease, angina, stroke, and transient ischaemic attack. MATERIAL AND METHODS: A cross-sectional study consisting of 5,186 hypertensive patients was conducted from July to November 2004 in Beijing and Shanghai, China. PAD was defined as an ankle-brachial index < or = 0.90 in either leg. RESULTS: The prevalence of PAD was 29.0% among hypertensive patients with known CVD, higher than in patients without known CVD (16.6%, P <0.0001). After multivariable logistic regression analysis, older age and current smoking were independently associated with prevalent PAD among all hypertensive patients.Among hypertensive patients without known CVD, higher total cholesterol (OR and 95% CI: 1.518, 1.162-1.984 in men and 1.460, 1.097-1.944 in women), was independently associated with prevalent PAD. Higher fasting glucose (OR and 95% CI: 1.027, 1.001-1.054 in men and 1.033, 1.006-1.061 in women) and higher uric acid (OR and 95% CI: 1.002, 1.001-1.003 in men and 1.003, 1.001-1.005 in women) were risk factors for PAD among hypertensive patients with known CVD. No association was found between obesity and PAD in hypertensive patients with and without known CVD. CONCLUSIONS: Prevalence of and risk actors for PAD among Chinese hypertensive patients with and without CVD were different. Cessation of smoking should be stressed to inhibit the progression of PAD in hypertensive patients.

Effects of sea anemone toxin anthopleurin-Q on potassium currents in rats and guinea pig ventricular myocytes / 老年心脏病学杂志（英文版）

To investigate the effect of sea anemone toxin anthopleurin-Q (AP-Q) on potassium currents in isolated rats and guinea pig ventricular myocytes.Methods The ventricular cells of guinea pigs and SD rats were obtained by enzymatic dissociation method.Whole cell patch clamp technique was used to record potassium currents (Ito,IK,and IK1).Results AP-Q 3-100 nmol/L increased Ito in a concentration-dependent manner,with an EC50 value of 12.7 nmol/L.At a potential of +50mV,AP-Q 10nmol/L increased Ito from (13.3±3.4) pA pF-1 to (19.46±4.3) pA pF-1.AP-Q 0.1-100 nmol/L increased IK and IK tail in a concentration-dependent manner with EC50 values of 4.7 nmol/L and 5.0 nmol/L,respectively.AP-Q 1 pmol/L-100 nmol/L increased IK1 in dose-dependent manner,with an EC50 of 0.2 nmol/L.Conclusions The effect of AP-Q on Ito,IK and IK1 may partly explain its mechanism in shortening APD and increasing RP.(J Geriatr Cardiol 2008;5:243-247)

Risk factors of peripheral arterial disease and relationship between low ankle - brachial index and mortality from all-cause and cardiovascular disease in Chinese patients with type 2 diabetes.

BACKGROUND: The aim of the present study was to evaluate the risk factors for peripheral arterial disease and the relationship between the ankle - brachial index (ABI) and mortality from all-cause and cardiovascular disease (CVD) in Chinese patients with type 2 diabetes mellitus (DM). METHODS AND RESULTS: ABI was identified at baseline by measuring systolic pressure in the bilateral brachial and tibial arteries. Mortality surveillance was completed from November 2004 to January 2006. Among 1,647 participants with type 2 DM at baseline, 531 (32.2%) were in the low-ABI group. Older age, female gender, higher serum level of total cholesterol, longer duration of DM and a history of smoking were associated with low ABI. During the 13-month follow-up, there were 132 deaths, of which 47 were from CVD. Low ABI was associated with mortality from all-cause and CVD, the adjusted relative risk of which was 1.851 (95% confidence interval 1.280-2.676) and 3.211 (1.703-6.053), respectively, in Cox regression models. The survival rate was significantly lower in the low-ABI group than in the normal-ABI group. CONCLUSION: Low ABI was independently associated with a high risk of all-cause and CVD mortality in Chinese patients with type 2 DM. ABI should be promoted as an ideal tool for predicting mortality in diabetic patients.

Evaluation of medical treatment for peripheral arterial disease in Chinese high-risk patients.

BACKGROUND: Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis and is associated with elevated cardiovascular morbidity and mortality. The aim of the present study was to evaluate the use of antiplatelet agents, statins and angiotensin-converting enzyme inhibitors (ACEI) in Chinese high-risk cardiovascular (CV) patients with PAD, with an emphasis on the need for aggressive medical management of all atherosclerotic manifestations. METHODS AND RESULTS: Medical records from 5,263 Chinese patients at high risk of CV were evaluated for the use of antiplatelet agents, statins and ACEI in patients with and without PAD. PAD was defined as an ankle-brachial index (ABI)<0.9 in either leg. Multivariable logistic regression analyses were performed to compare medication use in the 2 groups. A total of 5,254 patients were analyzed (52.9% male, mean age 67.3 years). The prevalence of PAD in the total patient group was 25.4%; 22.5% of them had PAD only. Overall, 5.7% had PAD only, 19.6% had PAD and coronary heart disease (CHD) or stroke or diabetes, 7.7% had CHD only, 12.6% had stroke only, and 13.6% had diabetes only. The 28.9% subjects having none of PAD, CHD, stroke or diabetes were used as the reference group. Only 65%, 37% and 47% of all patients received antiplatelet agents, statins and ACEI, respectively. Antiplatelets, statins, ACEI and all 3 medications were used less frequently in PAD only patients (58.1%, 35.9, 53.5% and 21.6%) vs CHD only (90.9%, 74.5%, 70.6% and 55.9%, p<0.001). All 3 proven efficacious therapies were prescribed for only 56% of patients with CHD only, 8% with stroke only, 13% with diabetes only and 21% with PAD only. CONCLUSION: PAD is prevalent in Chinese high-risk CV patients, equivalent to CHD, but these patients receive less intensive treatment than those with CHD. Programs to improve CV risk reduction in these high-risk patients are needed.

The relationship of ankle brachial index to all-cause and cardiovascular disease mortality in Chinese male patients with hypertension / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the risk factors for peripheral arterial disease (PAD) and the relationship of low ankle brachial index (ABI) to all-cause and cardiovascular disease (CVD) mortality in Chinese male patients with hypertension.</p><p><b>METHODS</b>The data of 1606 male participants with hypertension from the eight hospitals in Beijing and Shanghai were analyzed. ABI was ascertained at baseline by measuring the systolic pressures on bilateral brachial and tibial arteries. ABI < or = 0.9 was used as the diagnostic criteria for PAD identification. The follow-up survey was conducted from November 2005 to January 2006.</p><p><b>RESULTS</b>Of 1606 male participants with hypertension at baseline, 406 (25.3% ) were in low-ABI group and 1200 (74.7%) were in normal-ABI group. Older age, TC, history of diabetes, history of smoking and 2-grade hypertension were associated with low ABI in male patients with hypertension. During the (12.87 +/- 2.94) months follow-up, there were 153 deaths. Of which, 62 were attributable to CVD. Low ABI was associated with adjusted all-cause and CVD mortality risk of 1.728 (1.223-2.441) and 2.388 (1.409-4.046) respectively in Cox regression models. Rate of survival for the low-ABI group was significantly worse than for the normal-ABI group. The risk of all-cause and CVD mortality was increased with the decline of ABI.</p><p><b>CONCLUSION</b>Low ABI is independently associated with the high risks of all-cause and CVD mortality in Chinese male patients with hypertension. The utility of ABI as a tool for predicting mortality in the patients with hypertension should be popularized.</p>

[Study on the independent association of uric acid levels with peripheral arterial disease in Chinese patients with coronary heart disease].

OBJECTIVE: To evaluate the relationship between uric acid (UA) and peripheral arterial disease (PAD) in Chinese patients with coronary heart disease (CHD). METHODS: UA levels and PAD were evaluated in 3251 Chinese hospitalized patients with CHD (age > or = 50 years). PAD was diagnosed when the ankle-brachial index was < 0.9 but patients with an ankle-brachial index of > 1.4 were excluded because of false negative rate. Potential confounding variables with P < 0.10 were adjusted for multivariate analysis. RESULTS: In univariate analysis, UA levels were higher in patients with PAD than in those without PAD (349.80 micromol/L +/- 128.45 micromol/L vs. 323.00 micromol/L +/- 110.72 micromol/L, P < 0.001). Rate of hyperuricemia in patients with PAD and without PAD were 31.62% and 22.48% (P < 0.001) respectively. Prevalence rates of PAD for quintiles of UA level were 23.2%, 27.4%, 36.1%, 43.2% and 72.7%, respectively (P-trend < 0.05). With UA level as a continuous variable, the multivariate-adjusted odds ratio for PAD was 1.002 (95% confidence interval: 1.001 - 1.002) (P < 0.001). The optimal cut-off point for UA as determined by the receiver operating characteristic curve, was 227.2 micromol/L. The sensitivity and specificity at this cut-off point were 84.6% and 20.3%, respectively. The area under curve was 0.521 (95% confidence interval: 0.504 - 0.547) and the multivariate-adjusted odds ratio for PAD for UA above this level was 1.292 (95% confidence interval: 1.047 - 1.596) (P < 0.01). The results, however, after exclusion those cases who used diuretics, were similar. CONCLUSION: Elevated uric acid level seemed a significant and independent risk factor for PAD in Chinese hospitalized patients with CHD (age > or = 50 years).

Ankle brachial index as a marker of atherosclerosis in Chinese patients with high cardiovascular risk.

To obtain reliable data on the epidemiology, co-morbidities and risk factor profile of peripheral arterial disease (PAD), we evaluated the clinical significance of the ankle brachial index (ABI) as an indicator of PAD in Chinese patients at high cardiovascular (CV) risk. ABI was measured in 5,646 Chinese patients at high CV risk, and PAD was defined as an ABI<0.9 in either leg. Multivariable logistic regression analyses were performed to identify factors associated with PAD. A total of 5,263 patients were analyzed, 52.9% male, mean age 67.3 years, mean body mass index (BMI) 24.2 kg/m2, mean systolic/diastolic blood pressure (SBP/DBP) 139/80.7 mmHg. The prevalence of PAD in the total group of patients was 25.4%, and the prevalence was higher in females than in males (27.1% vs. 23.9%; odds ratio [OR]: 1.64). Patients with PAD were older than those without PAD (72.3+/-9.9 years vs. 65.6+/-11.7 years; OR: 1.06), and more frequently had diabetes (43.3% vs. 31.3%; OR: 2.02), coronary heart disease (CHD) (27.0% vs. 18.8%; OR: 1.67), stroke (44.4% vs. 28.3%; OR: 1.78), lipid disorders (57.2% vs. 50.7%; OR: 1.3) and a smoking habit (42.7% vs. 38.6%; OR: 1.52). The ORs for the PAD group compared with the non-PAD group demonstrated that these conditions were inversely related to ABI. Statin, angiotensin-converting enzyme-inhibitors and antiplatelet agents were only used in 40.5%, 53.6% and 69.1% of PAD patients, respectively. The data demonstrated the high prevalence and low treatment of PAD in Chinese patients at high CV risk. A lower ABI was associated with generalized atherosclerosis. Based on these findings, ABI should be a routine measurement in high risk patients. Aggressive medication was required in these patients.

A novel variable number of tandem repeat polymorphism of the renin gene and essential hypertension.

The aims of the present study were to find new genetic markers of essential hypertension (EH) and to investigate relationships between EH and polymorphisms of the renin gene. Using single strand conformation polymorphism, we discovered a new variable number of tandem repeat (VNTR) polymorphism in intron 7 that is 18 bp upstream from the boundary with exon 8. Nucleotide sequencing revealed that this VNTR polymorphism is a tandem repeat of the 4-nucleotide sequence TCTG. There were 6 alleles of this VNTR polymorphism, ranging from 7 repeats to 12 repeats. We analyzed the association between EH and this VNTR polymorphism. There was no significant difference in the overall distribution of this VNTR polymorphism between the EH and normotensive subjects. In summary, we discovered a novel VNTR polymorphism in the renin gene, and this polymorphism was not associated with EH.

Haplotype analysis of the human renin gene and essential hypertension.

The human renin gene is an attractive candidate for involvement in the underlying cause of essential hypertension (EH). Despite extensive examination, the relation between the renin gene and hypertension remains unclear. The aims of the present study were to discover new genetic markers of EH and to investigate the relations between polymorphisms of the renin gene and EH in the Japanese. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we isolated 3 novel variants of the renin gene; a single nucleotide polymorphism (SNP) in intron 4 (T+17int4G), a variable number of tandem repeats (VNTR) polymorphism in intron 7, and a missense mutation in exon 9 (G1051A). We performed an association study with these polymorphisms in 212 patients with EH and 209 age-matched normotensive (NT) subjects. The frequency of genotypes VNTR and T+17int4G did not differ significantly between the 2 groups, whereas the overall distribution of G1051A was significantly different between EH and NT. Haplotype analysis revealed that the overall distribution of haplotypes differed significantly between the EH and NT groups. PRA levels in patients with EH with the G/G genotype were significantly higher than in subjects with EH with G/A and A/A genotypes. These data suggest that the missense mutation in exon 9 may affect the enzymatic function of renin and consequently may be involved in the etiology of hypertension.

Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension.

Prostacyclin inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. The prostacyclin synthase (PGIS) gene is a candidate gene for cardiovascular disease. The purpose of this study was to locate possible mutations in the PGIS gene related to hypertension and cerebral infarction. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a T to C transition at the +2 position of the splicing donor site of intron 9 in patients with essential hypertension (EH). In vitro expression analysis of an allelic minigene consisting of exons 8-10 revealed that the nucleotide transition causes skipping of exon 9. This in turn alters the translational reading frame of exon 10 and introduces a premature stop codon (TGA). A three-dimensional model shows that the splice site mutation produces a truncated protein with a deletion in the heme-binding region. This splice site mutation was found in only one subject in 200 EH patients and 200 healthy controls. Analysis of the patient's family members revealed the mutation in two of the three siblings. The urinary excretion of prostacyclin metabolites in subjects with the mutation was significantly decreased. All subjects displaying the splice site mutation in the PGIS gene were hypertensive. In this study, we report a novel splicing mutation in the PGIS gene, which is associated with hypertension in a family. It is thought that this mechanism may involve in the pathophysiology of their hypertension.