Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes

Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes. We studied the hemodynamic effects of chronic oral supplementation in this condition. Thirty patients, 45 to 70 years of age, with type 2 diabetes, were randomly assigned in a double-blind manner to receive 500 mg ascorbic acid daily by mouth or placebo. Patients were studied at baseline and after 4 weeks of assigned treatment. The central aortic augmentation index (AgIx) and the time to wave reflection (Tr) were derived from radial artery pulse wave analysis data. AgIx and Tr were used as measures of systemic arterial stiffness and aortic stiffness, respectively. Ascorbic acid decreased brachial systolic blood pressure from 142.1+/-12.6 (SD) to 132.3+/-12.1 mm Hg (difference [95% CI] 9.9 [4.7, 15.0]; P<0.01), brachial diastolic pressure from 83.9+/-4.8 to 79.5+/-6.0 mm Hg (4.4 [1.8, 7.0]; P<0.01), and AgIx from 26.8+/-5.5% to 22.5+/-6.8% (4.3 [1.5, 7.1]; P<0.01). Tr increased from 137.1+/-12.6 to 143.4+/-9.2 ms (-6.3 [-10.1, -2.5]; P<0.01). Placebo had no hemodynamic effects, and this difference between treatments was significant (P<0.01 for blood pressure and Tr, P=0.03 for AgIx). We have therefore shown that after 1 month, oral ascorbic acid lowered arterial blood pressure and improved arterial stiffness in patients with type 2 diabetes. As strict control of blood pressure reduces cardiovascular risk in diabetes, ascorbic acid supplementation may potentially be a useful and inexpensive adjunctive therapy. Larger and longer studies now need to be performed.     

Plasma homocysteine and folate are related to arterial blood pressure in type 2 diabetes mellitus

The aim of this study was to assess the relationship between homocysteine (tHcy), folate and vitamin B₁₂ levels, urinary albumin excretion, and arterial blood pressure in patients with non–insulin-dependent diabetes mellitus (NIDDM). Our study was carried out in 33 NIDDM patients (16 men, 17 women) and 16 healthy volunteers as controls (seven men, nine women). Fasting and postmethionine load plasma tHcy levels were assessed, together with folate, vitamin B₁₂, and urinary albumin excretion levels. In NIDDM patients, there were correlations between folate and mean arterial pressure (r = −0.352, P = .046), folate and systolic blood pressure (r = −0.437, P = .013), folate and vitamin B₁₂ (r = 0.499, P = .004), tHcy and vitamin B₁₂ (r = −0.348, P = .04), ln tHcy and ln folate (r = −0.404, P = .01), and, lastly, between tHcy, either fasting or postload, and urinary albumin excretion. Patients with elevated tHcy levels had significantly higher diastolic blood pressure (P = .04) and mean arterial pressure (P = .03). Otherwise, higher folate values were associated with lower systolic blood pressure (P = .004) and mean arterial pressure (P = .02). In addition, NIDDM patients with complications presented higher tHcy basal values than the group without complications (P = .003). A particular propensity of such patients towards endothelial dysfunction could explain the presence of correlations between these metabolic parameters and arterial blood pressure.     

Impact of mean arterial blood pressure on higher arterial stiffness indices in South Asians compared to white Europeans

BACKGROUND: The pathophysiology of excessive premature coronary heart disease mortality among South Asians living in Britain remains unclear. We hypothesized that higher measures of arterial stiffness among South Asians compared with their white European counterparts would reflect an earlier progression of atherosclerosis, even in the absence of established coronary heart disease risk indices. METHODS: Arterial stiffness was measured by digital volume pulse photoplethysmography in 90 healthy South Asians and compared with 62 matched white Europeans in a temperature-controlled environment using a direct, standardized approach. RESULTS: Both ethnic groups were comparable for coronary heart disease risk profiles and had similar 10-year coronary heart disease risk estimates, but South Asians had a greater mean (SD) stiffness index compared with white Europeans [9.39 (0.22) vs. 8.43 (0.23) m/s; P = 0.007]. On linear regression analysis, mean arterial blood pressure (beta = 0.06; P = 0.03) and age (beta = 0.11; P = 0.002) were independent predictors of arterial stiffness in South Asians. Among white Europeans, age was an independent predictor of arterial stiffness (beta = 0.05; P = 0.01). CONCLUSION: Healthy South Asians have increased systemic arterial stiffness measured by stiffness index compared with white Europeans. There was an adverse and disproportional impact of age and mean arterial pressure on the vascular system in South Asians. Increased indices of arterial stiffness may explain their increased susceptibility to coronary heart disease.     

Assessment of toe blood pressure is an effective screening method to identify diabetes patients with lower extremity arterial disease

The authors evaluated a screening program for lower extremity arterial disease (LEAD) in diabetic patients and focused on the value of toe blood pressure assessment. They recruited 437 subjects, ages 30-70 years (134 healthy controls, 166 type 1 and 137 type 2 diabetic patients; control [Ctr], DM1, and DM2) with no previous history of LEAD. They were enrolled in a longitudinal study with a planned follow-up of 10 years. Patients were consecutively enrolled from outpatient diabetes units of 2 university hospitals. Subjects were screened with respect to peripheral circulation by use of established noninvasive techniques. These included arm, ankle (AP), and toe (TP) blood pressure measurements; evaluation of peripheral neuropathy; and a standardized physical examination. Results from the baseline examination are presented in this report. The number of patients who presented peripheral pressures or indices below normal (< mean -2 SD for controls) was higher among diabetic patients; 24% of DM1 and 31% of DM2, as compared to 6% of Ctr, had at least 1 lower limb with a low TP, AP, toe/arm index (TI), or ankle/arm index (AI), and these subjects were mainly identified by using the toe/arm index. TI was independently and negatively associated with fasting blood glucose in both patient groups, and with smoking, age, and diabetes duration in DM1. The mean AP was higher in the DM1 and DM2 groups compared to Ctr, whereas overall TP, TI, and AI were similar in the groups. It was also shown that abnormally low TI was significantly more common than low AI among diabetics (p<0.001), and this was true for TP vs AP as well (p<0.05). It is beneficial to include assessment of toe blood pressure and toe/arm blood pressure index to detect early LEAD in diabetic patients. Ankle blood pressure and indices alone are less efficient, owing probably to medial sclerosis in diabetic patients. Up to 30% of diabetic patients with no ischemic symptoms may have signs of impaired arterial circulation.     

Valsartan improves arterial stiffness in type 2 diabetes independently of blood pressure lowering

Increased arterial stiffness, as estimated from aortic pulse wave velocity (Ao-PWV), and albuminuria are independent predictors for cardiovascular disease in type 2 diabetes mellitus (T2DM). Whether angiotensin receptor blockers (ARBs), drugs with cardio-renal protective effects, improve Ao-PWV to a greater extent than other equipotent antihypertensive medications remains unclear. After a 4-week washout phase, we compared the effects of valsartan (n=66), an ARB, with that of amlodipine (n=65), a calcium channel blocker on Ao-PWV in 131 T2DM patients with pulse pressure (PP) >or=60 mm Hg and raised albumin excretion rate (AER) in a 24-week randomized, double-blind, parallel group study. Hydrochlorothiazide (HCTZ) 25 mg/d was added to valsartan 160 mg and amlodipine 5 mg/od uptitrated to 10 mg/od after 4 weeks to ensure equivalent BP control. After 24 weeks brachial and central aortic PP had fallen to a similar extent with attained mean (SD) brachial and central PP of 61.6 (13.6) and 47.3 (14.1) mm Hg in the valsartan/HCTZ group and 61.5 (12.2) and 47.3 (9.9) mm Hg in the amlodipine group, respectively. Ao-PWV showed a significantly greater reduction, mean (95% CI), -0.9 m/s (-1.4 to -0.3) for valsartan/HCTZ compared to amlodipine (P=0.002). AER fell significantly only with Val/HCTZ from 30.8(20.4, 46.5) to 18.2(12.5, 26.3) mcg/min, (P=0.01) with between treatment difference in favor of Val/HCTZ of -15.3mcg/min (P<0.001). Changes in AER and Ao-PWV were not correlated. Valsartan/HCTZ improves arterial stiffness and AER to a significantly greater extent than amlodipine despite similar central and brachial BP control. These 2 effects, which appear independent of each other, may explain the specific cardio-renal protective properties of ARBs.     

Higher systemic arterial compliance is associated with greater exercise time and lower blood pressure in a young older population.

OBJECTIVES: Arterial compliance is an important therapeutic target in older individuals in whom stiffening of the proximal arterial circulation is thought to underlie systolic hypertension and increased cardiac work. We have shown previously that arterial compliance is related to aerobic fitness and that it is increased in young (20 to 35 years old), previously sedentary individuals by a 4-week period of moderate aerobic training. The extent to which compliance relates to exercise performance in a random selection of young older patients has not been reported previously. Therefore, we examined the interrelationship between systemic arterial compliance (SAC) and time to cessation of exercise during a standard treadmill exercise test in an older population. DESIGN: A cross-sectional survey. METHODS: SAC was estimated at rest using simultaneous recordings of ascending aortic flow and carotid applanation tonometry in 43 subjects aged 67 +/- 7 years (mean +/- SD; 24 men and 19 women). Treadmill exercise testing was performed using a modified Bruce protocol. Aerobic capacity was assessed as Heart Rate-Blood Pressure product and exercise tolerance as total treadmill time. RESULTS: SAC and exercise tolerance were related to gender, with men exhibiting greater exercise reserve and higher SAC than women. There was a significant positive correlation between SAC and time to cessation of exercise (r = .34; P = .03), with a negative correlation between SAC and resting heart rate-blood pressure product (r = -.66; P < .001). SAC was correlated with height and blood pressure. Exercise tolerance was related to height (P < .02). CONCLUSIONS: These data indicate a positive association between SAC and fitness level in healthy older people and an inverse association between SAC and systolic blood pressure. Our findings are consistent with either (1) acquisition of a more compliant circulation and lower blood pressure through more physical activity or (2) that a more compliant arterial circulation and lower blood pressure permit greater athletic performance.     

Systolic blood pressure response to exercise in type 1 diabetes families compared with healthy control individuals

OBJECTIVE: Oxidative stress is increased in type 1 diabetes families. Since oxidative damage is a mediator of vascular injury and familial predisposition to hypertension increases the risk of hypertension and diabetic nephropathy, we studied blood pressure responses to exercise and cardiovascular risk factors in type 1 diabetes families. METHODS: Thirty-five type 1 patients, 74 first-degree relatives, and 95 healthy individuals without established coronary heart disease underwent a cycle ergometer test. Examination included medical history, lifestyle questionnaire, body weight, blood pressure, and laboratory tests [fasting plasma glucose and insulin, haemoglobin A1c (HbA1c), plasma lipids, C-reactive protein, fibrinogen, folate, plasma thiols, and albumin excretion rate]. RESULTS: Diabetic patients had higher plasma glucose, HbA1c, folate, and albuminuria, while lower plasma thiols than controls; relatives differed from controls in higher plasma total cholesterol and albuminuria, lower plasma thiols. No patient presented exercised-induced angina. Diabetic patients achieved a higher maximal exercise systolic blood pressure (similar workload); systolic pressure remained high during recovery. Relatives showed higher values of systolic pressure at peak exercise (same workload). The following were associated with an abnormal blood pressure response to exercise: diastolic blood pressure and HbA1c in the control sample; disease duration and fibrinogen in the diabetic group; plasma low-density lipoprotein (LDL) cholesterol, body mass index (BMI), housework, and plasma thiols among relatives. CONCLUSION: An abnormal blood pressure response to exercise testing has been identified for the first time in asymptomatic normotensive non-diabetic relatives of type 1 diabetics, which was associated with indices of metabolic syndrome and oxidative damage. Moreover, in healthy normotensive non-diabetic control individuals (without a family history of type 1 diabetes), the systolic blood pressure response to exercise was significantly correlated with HbA1c levels.     

Limb venous compliance responses to lower body negative pressure in humans with high blood pressure

This study tested the hypothesis that limb venous responses to baroreceptor unloading are altered in individuals with high blood pressure (HBP) compared with normotensive (NT) controls. Calf venous compliance was assessed in 20 subjects with prehypertension and stage-1 hypertension (mean arterial pressure, MAP: 104±1?mm?Hg) and 13 NT controls (MAP: 86±2?mm?Hg) at baseline and during lower body negative pressure (LBNP), using venous occlusion plethysmography. Baroreflex sensitivity (BRS) was measured using the sequence technique and total peripheral resistance (TPR) was estimated from finger plethysmography. Baseline venous compliance was not different between groups, but the HBP group had lower baseline lnBRS (2.22±0.14 vs 2.7±0.18?ms?mm?Hg(-1)) and greater baseline TPR (3828±138 vs 3250±111?dyn?sec(-1)?cm(-5)?m(2), P<0.05). Calf venous compliance was reduced in response to LBNP only in the NT group (P<0.05). The HBP group had a greater increase in TPR (ΔTPR) compared with the NT group (+1649±335 vs +718±196?dyn?sec(-1)?cm(-5)?m(2), P<0.05). In conclusion, the early stages of hypertension are characterized by an attenuated venoconstrictor response to baroreceptor unloading, which may compensate for an exaggerated vasoconstrictor response and protect against further increases in blood pressure.     

血压正常高值者动态血压变化与动脉顺应性的相关性研究

目的探讨血压正常高值者24 h动态血压变化与颈桡动脉脉搏波传导速度(crPWV)、颈动脉内膜中层厚度(IMT)的相关性。方法入选受试对象286例,其中理想血压组(血压<120/80 mm Hg,1 mm Hg=0.1 33 kPa)90例,血压正常高值组196例,对所有入选对象进行24 h动态血压监测,根据监测参数将血压正常高值组又分为杓型组103例,非杓型组93例,同时进行crPWV及颈动脉IMT检测。结果非杓型组24h收缩压均值较杓型组升高[(122.00)±9.74)mm Hg vs(11 6.74±8.66)mm Hg,P<0.05]。非杓型组夜间血压各指标均较杓型组明显升高(P<0.01),非杓型组crPWV较杓型组升高[(9.53±1.14)m/s vs(8.38±0.88)m/s.P<0.05],非杓型组IMT较杓型组升高[(0.93±0.11)mm vs(0.81±0.1 2)mm,P<0.05],多元回归分析显示,夜间收缩压均值、夜间收缩压下降率、夜间舒张压均值等是crPWV的影响因素,夜间舒张压下降率、24 h收缩压均值、甘油三酯是IMT的影响因素。结论血压昼夜节律异常与crPWV及IMT密切相关,血压正常高值者已出现血管结构与弹性功能异常。     

Uncontrolled home blood pressure in the morning is associated with nephropathy in Japanese type 2 diabetes

The purposes of this study were to investigate the state of blood pressure control level and to investigate the relationship between blood pressure control level and nephropathy in Japanese type 2 diabetes. We measured clinic and home blood pressure in 923 type 2 diabetic patients. According to the criteria for hypertension in the Japanese Society of Hypertension Guidelines 2009, patients were classified into four groups by clinic systolic blood pressure (130 mmHg) and morning systolic blood pressure (125 mmHg), as follows: controlled hypertension (CH), white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH). Of all patients, 13.9, 12.6, 13.3, and 60.2% were identified as having CH, WCH, MH, and SH, respectively. The average number of drugs prescribed was 1.8. We assessed the association between blood pressure control level and nephropathy in diabetic patients. The degree of urinary albumin excretion and the prevalence of nephropathy in diabetic patients were higher in MH and SH groups than those in the CH group. The majority of patients had poor blood pressure control, regardless of ongoing conventional antihypertensive therapy, and diabetic patients with MH and SH were associated with nephropathy. It is suggested that more aggressive antihypertensive treatment is recommended to prevent nephropathy in diabetic patients.     

Assosiation of angiopoietin-like protein 2with lower extremity arterial disease in type 2 diabetes mellitus

<正>Objective To study the assosiation of angiopoietinlike protein 2(ANGPTL2)with lower extremity arterial disease in type 2 diabetes mellitus.Methods A total of360 type 2 diabetic patients were divided into three groups:without(group A),with mild to moderate(group B),and severe(group C)lower extremity arterial disease according to the ankle brachial index.And,120     

Sex-influenced association of metabolic syndrome with lower extremity arterial disease in type 2 diabetes

AimThe present study is undertaken to investigate the relationship between metabolic syndrome (MS) and lower extremity arterial disease (LEAD) in type 2 diabetes mellitus (T2DM) patients.MethodsA multi-center cross-sectional study was conducted on 8374 T2DM patients (4521 males and 3853 females) from 30 hospitals across China from June 2016 to January 2017. The odds ratios (ORs) and 95% confidence intervals (CIs) were presented to show the association between MS and LEAD. The univariate and multiple logistic analyses were performed to examine the association between MS and the prevalence of LEAD. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on the number and individual of MS components.ResultsFinally, 1809(21.60%) T2DM patients meet the diagnostic criteria of LEAD. Of the 3853 female subjects, 841(21.83%) patients were in the LEAD group and of the 4521 male subjects, 968(21.41%) patients were in the LEAD group. When adjusting for confounding variables, MS was significantly associated with the prevalence of LEAD in all enrolled T2DM patients (OR = 1.22, 95%CI: 1.09–1.37, P = 0.001). However, upon analyzing LEAD in different sex groups, the significant association remained in females (OR = 1.33, 95%CI: 1.12–1.58, P < 0.001), but not in males (OR = 1.11, 95%CI: 0.95–1.29, P = 0.202).ConclusionsOur results suggest that MS is specifically associated with an increased risk of LEAD in female T2DM patients. However, MS may not be a significant factor in the prevalence of LEAD in male T2DM patients.     

Androgen deprivation in males is associated with decreased central arterial compliance and reduced central systolic blood pressure

The higher incidence of coronary artery disease in men is often attributed to androgens. Arterial compliance or 'stiffness' is increasingly regarded as a modifiable risk factor for cardiovascular disease. We wanted to look at the effects of complete androgen withdrawal, on arterial compliance in men. We performed arterial compliance studies on 12 men with complete androgen deprivation as treatment for prostate cancer, and on 12 age-matched healthy controls. Central pulse wave velocities were significantly higher in the androgen-deprived men (14.2 +/- 2.7 vs 11.8 +/- 1.6 m/sec, P = 0. 02). The cases tended to have higher brachial systolic pressures than controls though this difference was not significant (P = 0.2). We conclude that androgen withdrawal is associated with a reduction in central arterial compliance. Conversely androgen withdrawal does not affect peripheral arterial compliance. It is unlikely that the presence of normal concentrations of androgens can explain the sex difference in mortality rates. Longitudinal studies are needed for further evaluation. Journal of Human Hypertension (2000) 14, 395-397