The association between circulating endostatin and a disturbed circadian blood pressure pattern in patients with type 2 diabetes.

BACKGROUND: Endostatin, cleaved from collagen XVIII in the extracellular matrix, is a promising circulating biomarker for cardiovascular damage. It possesses anti-angiogenic and anti-fibrotic functions and has even been suggested to be involved in blood pressure regulation. Less is known if endostatin levels relate to circadian blood pressure patterns. In the present paper we studied the association between circulating levels of endostatin and nocturnal dipping in blood pressure. METHODS: We used the CARDIPP-study, a cohort of middle aged, type 2 diabetics (n = 593, 32% women), with data on both 24-hour and office blood pressure, serum-endostatin, cardiovascular risk factors, and incident major cardiovascular events. Nocturnal dipping was defined as a >10% difference between day- and night-time blood pressures. RESULTS: Two-hundred four participants (34%) were classified as non-dippers. The mean endostatin levels were significantly higher in non-dippers compared to dippers (mean ± standard deviation: 62.6 ± 1.8 µg/l vs. 58.7 ± 1.6 µg/l, respectively, p = .007). Higher serum levels of endostatin were associated with a diminished decline in nocturnal blood pressure adjusted for age, sex, HbA1c, mean systolic day blood pressure, hypertension treatment, glomerular filtration rate, and prevalent cardiovascular disease (regression coefficient per SD increase of endostatin -0.01, 95% CI, -0.02-(-0.001), p = .03). Structural equation modelling analyses suggest that endostatin mediates 7% of the association between non-dipping and major cardiovascular events. CONCLUSION: We found an independent association between higher circulating levels of endostatin and a reduced difference between day- and night-time systolic blood pressure in patients with type 2 diabetes. Yet endostatin mediated only a small portion of the association between non-dipping and cardiovascular events arguing against a clinical utility of our findings.

Independent association between age and circadian systolic blood pressure patterns in adults with hypertension.

Previous studies indicate a preliminary association between age and circadian blood pressure (BP) variation. This association would be affected by confounding factors in real-world populations. The authors investigated whether this is a convincingly independent association in a real-world population of adults with hypertension. Clinical data and findings of 24-hour ambulatory BP monitoring were obtained from 297 consecutive adults with hypertension (60.19±0.77 years). BP dipping patterns were categorized based on the percentage of nocturnal BP drop. Multivariate linear regression analysis identified an independent correlation between age and percentage of nocturnal systolic BPdrop (ß=-7.296; 95% CI, -10.430 to -4.162 [P<.001]). Reverse dippers were the oldest and extreme dippers were the youngest. A significant age difference was noted among patients grouped into four BP dipping patterns with and without adjustments for sex, body mass index, drugs, diabetes mellitus, smoking, 24-hour mean heart rate, and 24-hour mean systolic and diastolic BP.

Plasma Homocysteine Levels Are Associated With Circadian Blood Pressure Variation in Chinese Hypertensive Adults.

BACKGROUND: Homocysteine-lowering intervention with folate was recently shown to be able to increase day-night difference of blood pressure (BP) in humans indicating a potential relationship between homocysteine and circadian BP variation. We thus sought to investigate the association between plasma total homocysteine level (tHcy) and circadian BP variation in hypertensive adults. METHODS: We enrolled 244 eligible dipping and 249 nondipping BP status adults from 560 adults who were randomly sampled from 5,233 Chinese hypertensive adults who received ambulatory BP monitoring (ABPM). We further enrolled 390 adults with CC/CT genotypes of the methylenetetrahydrofolate reductase (MTHFR) and 79 TT genotype who received ABPM at the same time from 1858 hypertensive adults with MTHFR polymorphisms detection. RESULTS: Plasma tHcy in nondippers was significantly higher than dippers (P < 0.001). Simple linear analysis revealed that tHcy significantly correlated with nocturnal systolic BP fall (r = -0.145, P = 0.001) and diastolic BP fall (r = -0.141, P = 0.002). Multivariate logistic regression analysis further identified tHcy as an independent factor correlated with the presence of nondipping BP status in hypertensive adults (odds ratio: 1.873, 95% confidence interval: 1.171-2.996, P = 0.009). The percentage of dipping BP status was 19.49% or 8.86% and the percentage of nondipping BP status was 80.51% or 91.14% in CC/CT or TT genotypes, respectively. The above different between CC/CT and TT genotypes was significant (P = 0.024). CONCLUSIONS: These results indicated that high homocysteine levels associate with disturbed circadian BP variation in Chinese hypertensive adults.

Impact of night-time blood pressure on cerebral white matter hyperintensity in elderly hypertensive patients.

AIM: Cerebral white matter hyperintensity (WMH) is highly prevalent in the elderly population, and increases the risk of dementia and stroke. We investigated the relationship between ambulatory blood pressure monitoring levels and quantitatively measured WMH volumes among elderly hypertensive patients with well-controlled blood pressure (BP) to re-evaluated effective hypertension management methods to prevent the progression of WMH. METHODS: Participants comprised 84 hypertensive patients aged between 65 and 75 years without symptomatic heart failure, ischemic heart disease, atrial fibrillation, stroke or cognitive dysfunction. RESULTS: Linear regression analysis showed that office BP was not associated with WMH volume increases. Raised night-time systolic BP (P = 0.013) were associated with greater WMH volumes during ambulatory blood pressure monitoring. To clarify the effect of asleep systolic BP on WML volume, we then classified patients into two systolic BP groups as follows: <125 mmHg (n = 47) and ≥125 mmHg (n = 37). Baseline characteristics were almost similar in both groups, except the dipper type of circadian BP variation was significantly common in the group with night-time systolic BP <125 mmHg. However, WMH volume was greater in the group with night-time systolic BP ≥125 mmHg than that in the <125 mmHg group (9.0 ± 8.4 mL vs 4.1 ± 4.3 mL, P = 0.015). CONCLUSION: Higher night-time systolic BP levels were observed to contribute greater WMH volumes in elderly hypertensive patients. To prevent the progression of WMH, controlling BP on the basis of ambulatory blood pressure monitoring is important.

Effect of Highly Concentrated Carbon Dioxide-Bathing on Circadian Blood Pressure Variations in Drug-refractory Hypertensive, Specially Non-dipper Patients / 日本温泉気候物理医学会雑誌

Using a highly concentrated CO₂-bathing, authors studied an effect of the bathing (CO₂: 1, 000ppm, for 10min at 40°C) on circadian blood pressure in six cases of antihypertensive drug-refractory hypertension. The patients were females, ranging from 62 to 70 years old (mean age: 65.8±2.6). All of the patients were diagnosed as the III stage of essential hypertension (according to WHO criteria) and have been treated with captopril, nifedipine or α-methyl DOPA since three to ten years ago. Out of six cases five showed non-dipper pattern in circadian blood pressure. All bathings were done at 16:30 and comparative study of circadian blood pressure between plain water and CO₂-bathing was carried out.<br>The results obtained were as follows.<br>1) In five cases of non-dippers CO₂-bathing exerted the therapeutic effect upon the high blood pressure at night and resulted in the significant decrease in hyperbaric indici of systolic, mean and diastolic blood pressure, comparing with plain water-bathing. However, no significant difference of heart rate was observed between plain water and CO₂-bathing.<br>2) In a case of good responder to antihypertensive drug, a relatively low blood pressure continued all day after CO₂-bathing.<br>From these results it is expected that a highly concentrated CO₂-bathing is useful as supportive therapy to essential hypertension, specially to non-dipper.