Insulin resistance is associated with reduced nocturnal falls of blood pressure in normotensive, nonobese type 2 diabetic subjects

To assess the relationship between insulin resistance and ambulatory blood pressure (BP) pattern, we determined glucose infusion rate (GIR) as a marker of insulin resistance using a glucose clamp method, and measured 24-h BPs in 25 normotensive, nonobese type 2 diabetic subjects. They were divided into two groups: 11 dippers and 14 nondippers. Clinical characteristics were similar in the two groups except for orthostatic fall in systolic BP. The median GIR level was significantly lower in nondippers than in dippers (P < 0.05). Spearman's rank correlation revealed that the GIRs were negatively correlated with the systolic, diastolic and mean BPs during nighttime (P < 0.05 or less), but not with daytime or whole day BPs. Moreover, based on a logistic regression analysis, the GIR as well as orthostatic fall in systolic BP discriminated independently between dippers and nondippers. Thus, our results suggest that insulin resistance is associated with decreased nocturnal BP fall in type 2 diabetic subjects.     

Racial differences in nocturnal dipping status in diabetic kidney disease: Results from the STOP‐DKD (Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease) study

While racial variation in ambulatory blood pressure (BP) is known, patterns of diurnal dipping in the context of diabetic kidney disease have not been well defined. The authors sought to determine the association of race with nocturnal dipping status among participants with diabetic kidney disease enrolled in the STOP‐DKD (Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease) trial. The primary outcome was nocturnal dipping—percent decrease in average systolic BP from wake to sleep—with categories defined as reverse dippers (decrease <0%), nondippers (0%–<10%), and dippers (≥10%). Twenty‐four‐hour ambulatory BP monitoring was completed by 108 participants (54% were nondippers, 24% were dippers, and 22% were reverse dippers). In adjusted models, the common odds of reverse dippers vs nondippers/dippers and reverse dippers/nondippers vs dippers was 2.6 (95% confidence interval, 1.2–5.8) times higher in blacks than in whites. Without ambulatory BP monitoring data, interventions that target BP in black patients may be unable to improve outcomes in this high‐risk group.     

Association Between Nondipper Behavior and Serum Calcium in Hypertensive Patients with Mild-to-Moderate Chronic Renal Dysfunction

A nondipping BP pattern has been shown to be predictive of end-organ damage, cardiovascular events, and mortality. The mechanisms of blunted nocturnal BP fall are multifactorial. We assessed whether total corrected serum calcium and ionic calcium (iCa) are associated with a blunted nocturnal BP fall in both treated and untreated hypertensive patients with stages 1–3 of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI). Clinical data and 24-hour ambulatory blood pressure monitoring were obtained in a cohort of 231 essential hypertensive patients. Among the entire cohort, 107 were nondippers and 124 were dippers. Only in nondippers, we found significant correlations between iCa and 24-hour systolic blood pressure (SBP; r = 0.21, P < .03), diurnal SBP (r = 0.21, P < .03), and 24-hour pulse pressure (PP; r = 0.23, P < .02). The ambulatory arterial stiffness index (AASI) was significantly related with 24-hour PP in both dippers and nondippers after adjusting for age. Both AASI and 24-hour PP were higher in nondippers than in dippers. In addition, in nondippers, the prevalence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m² was higher than in dippers (50% vs. 33.7%, P < .02). Logistic regression showed that patients with eGFR ≥60 mL/minute/1.73 m² had lower risk of nondipper status than patients with eGFR <60 mL/minute/1.73 m² (odds ratio = 2.445; 95% confidence interval = 1.398–4.277, P < .002). In conclusion, serum iCa could participate in the pathogenesis of nondipping pattern. Increased large artery stiffness may be a mechanism of the deleterious influence of nondipping on cardiovascular outcome. Hypertensive subjects with stage 3 of NKF KDOQI had a greater loss of circadian BP rhythm than those in stages 1 and 2.     

Changes of nocturnal blood pressure dipping status in hypertensives by nighttime dosing of alpha-adrenergic blocker, doxazosin : results from the HALT study

Abnormal nocturnal blood pressure (BP) dipping status may be partly determined by nocturnal sympathetic activity. We studied the effect of nighttime dosing of an alpha(1)-adrenergic blocker, doxazosin, on the BP dipping status of 118 hypertensives, all of whom underwent 24-hour ambulatory BP monitoring before and after treatment. The mean nighttime/daytime ratio of systolic BP was increased (0.91 after therapy versus 0.89 at baseline, P<0.05). The patients were initially divided into 4 groups on the basis of their dipping status at the baseline assessment: 18 (15%) were extreme dippers, with a nighttime systolic BP fall of at least 20% of daytime BP; 46 (39%) were dippers (fall between 10% and 20%); 48 (41%) were nondippers (fall between 0% and 10%); and 6 (5%) were risers (nocturnal increase of systolic BP). A shift in dipping status toward less nocturnal BP dipping was observed after doxazosin therapy (P<0.05). Dipping status was determined by nighttime more than by daytime BP, and this was not explained by differences in the number of daytime and nighttime readings. The effects of doxazosin on the mean nocturnal systolic BP changes were an increase of 4.3 mm Hg in extreme dippers and decreases of 0.7 mm Hg in dippers, 12 mm Hg in nondippers, and 18 mm Hg in risers; the reduction was only significant in the latter 2 groups (both P<0.01). To estimate the effects of regression to the mean on the changes in dipping status, we also defined dipping status with the average of the BPs before and after doxazosin and found no difference in the degree of nighttime BP reduction among each group. The reduction of daytime BP was now significantly greater in the subgroups with less dipping: 6. 4 mm Hg for extreme dippers and 16 mm Hg for risers (P<0.05). In conclusion, nighttime dosing with doxazosin markedly affects the nocturnal BP dipping status of hypertensives, but the apparently greater reduction in nighttime pressure in nondippers and risers may be, at least partly, due to the effect of regression to the mean. The most important determinants of the effect of doxazosin were the absolute BP levels, both day and night, rather than dipping status per se.     

Role of insulin resistance in nondipper essential hypertensive patients.

In hypertensive patients, diminished nocturnal blood pressure (BP) fall is associated with poor prognosis for cardiovascular events. However, the relation of insulin resistance with the etiology of nondipper essential hypertension remains unclear. The aim of the present study was to assess the role of insulin resistance in diminished nocturnal BP fall, left ventricular hypertrophy (LVH), and increased plasma atrial (ANP) and brain natriuretic peptides (BNP) in essential hypertensive patients. One hundred and three patients with essential hypertension were divided into dippers (n = 57; age: 57 +/- 5 years, mean +/- SD) or age-matched nondippers (n = 46; 57 +/- 4 years), based on ambulatory BP (ABP) monitoring. Although the systolic and diastolic ABP values were similar during the day, those at night were higher in nondippers than in dippers ( p < 0.0001 for each). Echocardiographic findings revealed that the left ventricular mass index (LVMI) was higher in nondippers (p < 0.0001). Plasma ANP and BNP were also higher in nondippers (p < 0.0001 for each). Fasting plasma concentrations of glucose and insulin (p < 0.0001 for each) and the homeostasis model assessment (HOMA) index (p < 0.0001) were also higher in nondippers. Multivariate analysis revealed that systolic ABP at night was a significant factor for LVMI, ANP and BNP. In addition, the HOMA index was a significant factor for LVMI and BNP. These observations suggest that diminished nocturnal BP fall is closely related to the development of LVH with concomitant increase in BNP in essential hypertensive patients, and that insulin resistance may play a key role in these processes.     

The relationship between a blunted morning surge and a reversed nocturnal blood pressure dipping or “riser” pattern

The authors sought to determine the association between the blunted morning blood pressure (BP) surge and nocturnal BP dipping of the “riser” pattern in 501 patients with hypertension enrolled in the ACHIEVE‐ONE (Ambulatory Blood Pressure Control and Home Blood Pressure [Morning and Evening] Lowering by the N‐Channel Blocker Cilnidipine) trial. The patients' sleep‐trough morning BP surge and prewaking surge were calculated and then classified according to their nocturnal systolic BP reduction pattern as extreme dippers, dippers, nondippers, and risers. The prevalence of the riser pattern was significantly higher in both the lowest sleep‐trough morning BP surge decile and the prewaking surge decile (blunted surge group) compared with the remaining deciles (56.0% vs 10.4% [P<.0001] and 59.2% vs 10.2% [P<.0001], respectively). The riser pattern was a significant determinant of both blunted sleep‐trough morning BP surge (odds ratio, 73.3; P<.0001) and blunted prewaking surge (odds ratio, 14.8; P<.0001). The high prevalence of the riser pattern in patients with blunted morning BP surges may account for the cardiovascular risk previously reported in such patients.     

The majority of nondipping men do not have increased cardiovascular risk: a population-based study

OBJECTIVE : To investigate whether nondipping and diabetes are independently related to metabolic risk profile and prevalence of target organ damage in a population setting. METHODS : A population-based cohort of 70-year-old men (n = 1057) was examined with 24-h ambulatory blood pressure monitoring, euglycemic hyperinsulinemic clamp and lipid and glucose determinations. We defined nondipping as a night-day systolic blood pressure ratio >or= 1 (n = 66). Urinary albumin excretion rate and echocardiographically determined left ventricular geometry were used as indices of target organ damage. RESULTS : Nondipping was not related to hypertension, but diabetes was more common in nondippers (26%) than in dippers (14%, P < 0.05). Nondiabetic nondippers did not differ from dippers regarding insulin sensitivity, plasma glucose or lipids. However, nondipping in diabetic subjects was associated with the most pronounced impairments in body mass index, serum triglycerides and fasting plasma glucose. Measures of target organ damage did not differ between nondippers and dippers in the whole population, but an interaction (P < 0.05) between nondipping and diabetes contributed to an increased left ventricular mass in diabetic nondippers. The urinary albumin excretion rate was independently related to diabetes. CONCLUSIONS : In this population study, an interaction between diabetes and nondipping was demonstrated regarding fasting plasma glucose, lipid levels and left ventricular mass, indicating that nondipping is a marker of risk in diabetic subjects. However, in the nondiabetic majority of the population, nondipping was not associated with either metabolic disturbances or target organ damage.     

Neurohumoral characteristics of older hypertensive patients with abnormal nocturnal blood pressure dipping

Abnormal patterns of diurnal blood pressure (BP) variation have been reported to be related to advanced target organ damage and poor cardiovascular prognosis. However, the neurohumoral characteristics of patients with such variation have not been fully investigated. We measured BP and plasma levels of neurohumoral factors (norepinephrine [NE], epinephrine, renin, and arginine vasopressin [VP]) during the 70 degree head-up tilt test (10 min supine and 15 min tilting) in 120 older subjects (mean age 71 years) who had sustained hypertension as determined by ambulatory BP monitoring. They who were subclassified according to the nocturnal systolic BP fall as follows: 28 extreme dippers with >20% nocturnal BP fall; 78 dippers with >0% but <20% fall; and 14 nondippers with <0% fall. Plasma renin activity (r = 0.22, P = .02) and VP level (r = 0.36, P < .0001) after tilting were positively associated with the nocturnal systolic BP fall. Plasma NE levels were significantly higher in nondippers than in dippers in both the supine and tilting positions (supine 519 v 315 pg/mL, P = .001; tilting 803 v 550 ng/mL, P < .01), whereas the increase of NE induced by tilting was comparable in the two groups. Plasma renin activity in both the supine and tilting positions was comparable in the three groups, but the increase of this activity caused by tilting was less marked in the nondippers than in the extreme dippers (0.05 v 0.26 ng/mL/min, P = .02) and dippers (0.21 ng/mL/min, P = .07). Plasma VP was markedly increased after tilting in the extreme dippers compared with dippers (3.8 v 2.6 pg/mL, P < .001) and nondippers (v 2.0 pg/mL, P < .001), whereas the levels in the supine position were comparable in the three groups (2.0 pg/mL for extreme dippers, 1.9 pg/mL for dippers, 1.6 pg/mL for nondippers). In conclusion, diurnal BP variation in elderly hypertensive individuals was significantly associated with neurohumoral factors regulating circulating blood volume. Increased VP after tilting in extreme dippers might counteract reduced circulating blood volume, whereas nondippers appear to have alpha- and beta-adrenergic subsensitivity that may be induced by their chronic exposure to high NE levels.     

Insulin Resistance and Blood Pressure Circadian Variation in an Obese Hypertensive Population

Insulin resistance (IR) is related to arterial hypertension and target organ damage. Hypertensive individuals exhibiting a diminished nocturnal blood pressure (BP) reduction (non-dippers) have an increased incidence of cardiovascular events. The association, however, of IR with BP circadian variation has not been evaluated so far. Therefore, this study examined 226 (116 male and 110 female) overweight and obese subjects (BMI > 27kg/m²) with newly diagnosed essential hypertension who underwent clinical and laboratory evaluation, including an oral glucose tolerance test and ambulatory BP measurement (ABPM). IR was estimated using the homeostasis model assessment (HOMA-IR). The population was grouped according to HOMA-IR values > 2.75 (insulin resistance type) or < 2.75 (insulin sensitive type). Results. No significant differences were observed between dippers (n = 137) and non-dippers (n = 89) with respect to age, gender, BMI, serum cholesterol, triglycerides, LDL-C, and HDL-C levels, nor smoking habits. The proportion of IR subjects among dippers (59.1%) and non-dippers (56.7%) was similar (p = 0.833). Moreover, no significant association was found when the HOMA-IR was examined as a continuous component (p = 0.96). Conclusions. Insulin resistance is not associated with nocturnal blood pressure reduction in obese hypertensives. This may be explained by the notion that insulin secretion does not follow a circadian mode of variation.     

Insulin resistant state in type 2 diabetes is related to advanced autonomic neuropathy

To elucidate the relationships between obesity, glycemic control, dyslipidemia, hypertension, microvascular complications, and insulin resistance assessed using an euglycemic hyperinsulinemic clamp technique, we studied 54 hospitalized type 2 diabetic subjects (DM) and 10 age- and sex-matched normotensive, nonobese control subjects (C). Glucose infusion rate (GIR) derived from the clamp study was used as an index of insulin resistance. Body mass index (BMI), the prevalence of hypertension, HbA1c and serum nonesterified fatty acids (NEFA) were significantly higher, and serum high-density-lipoprotein (HDL)-cholesterol was significantly lower in DM than in C (p < 0.05 or less). The median GIR level was significantly lower inDM than in C (p = 0.038). The difference in GIR between the two groups wasstill statistically significant even after adjustment for BMI, mean BP, HbA1c, NEFA, and HDL-cholesterol. However, after simultaneous adjustment for these factors, there was no difference in GIR between the two groups. Body mass index, mean BP, HbA1c, and NEFA showed negative correlations, and serum HDL-cholesterol showed a positive correlation with GIR, but neither age nor duration of diabetes correlated with GIR. When GIR values in DM were divided according to the degree of neuropathy, retinopathy, and nephropathy, and compared to those in C, GIR levels tended to be decreased with increasing severity of each microvascular complication, but there was no difference in median GIR levels among the diabetic subgroups. Relationships between the GIR levels and confounding factors such as age, sex, BMI, mean BP, HbA1c, serum NEFA, and serum HDL-cholesterol, were examined simultaneously with a multiple regression analysis. This analysis revealed that HbA1c and serum NEFA may affect the GIR level. Furthermore, together with these two factors, the relationships between the GIR levels and the severity of each microvascular complication were explored with the same analysis. This model clearly demonstrated that both the decreased CVR-R and pronounced orthostatic fall in systolic BP were independent factors for the decreased GIR. These findings suggest that marked autonomic dysfunction, rather than other confounding factors, is related to increased insulin resistance in DM.     

Ambulatory Blood Pressure Variability Is Increased in Diabetic Hypertensives

The purpose of this study was to examine the possible difference in the 24-hr BP profile—including short-term BP variability, assessed as the standard deviation—between diabetic and non-diabetic hypertensives. We measured 24-hr ambulatory BP in 11 diabetic hypertensives (diabetic HT) and 10 non-diabetic hypertensives (non-diabetic HT) who were hospitalized for the educational program in our hospital and were under stable salt intake. Renal function and sleep apnea were also estimated. There were no significant differences in 24-hr systolic BP (141 mmHg vs. 135 mmHg, ns), daytime systolic BP (143 mmHg vs. 138 mmHg, ns), and nighttime systolic BP (135 mmHg vs. 130 mmHg, ns) between diabetic HT and non-diabetic HT. The values of 24‐hr HR (69.7 beats/min vs. 65.2 beats/min, ns) and 24-hr HR variability (9.9 beats/min vs. 10.1 beats/min, ns) were also similar between the groups. Interestingly, diabetic HT had a significantly greater 24-hr systolic and diastolic BP variability than non-diabetic HT (18.2 mmHg vs. 14.5 mmHg, p < 0.05; 11.5 mmHg vs. 9.6 mmHg, p < 0.05, respectively). The values for creatinine clearance, urinary protein excretion, and apnea-hypopnea index were similar between the groups. Bivariate linear regression analysis demonstrated that fasting blood glucose was the primary determinant of 24-hr diastolic BP variability (r = 0.661, p < 0.01). Multiple stepwise regression analysis revealed that fasting blood glucose was a significant and independent contributor to 24-hr systolic BP variability (r = 0.501, p < 0.05). Taken together, these results demonstrate that BP variability is increased in diabetic hypertensives. Furthermore, it is possible that an elevation of fasting blood glucose may contribute to the enhanced BP variability in hypertensives.     

Differential Effects of Amlodipine on Ambulatory Blood Pressure in Elderly Hypertensive Patients With Different Nocturnal Reductions in Blood Pressure

Previous studies have discovered that amlodipine given once daily can reduce blood pressure (BP) throughout the day and night. The effects of amlodipine on day and night BP have not been fully investigated in groups of hypertensives with different diurnal variations. In a prospective study, we performed 24-h ambulatory BP monitoring before and after once-daily use of amlodipine in three groups of asymptomatic elderly hypertensive patients with different nocturnal BP reductions, as follows: 10 extreme dippers with nocturnal reduction of systolic BP ≥ 20% of daytime systolic BP, 17 dippers (reduction by ≥ 10% to < 20%), and 23 nondippers (reduction by < 10%). At baseline, the office and the awake BP were similar in all three groups, whereas the nighttime BP was significantly higher in the nondippers than in the dippers and in the dippers than in the extreme dippers. After treatment, the office and the daytime BP were both equally reduced in all three groups. On the other hand, the nighttime BP was significantly reduced both in the nondippers and, to a lesser extent, in the dippers. In the extreme dippers, however, no further reductions of nocturnal BP were found. Significant positive correlations were found between baseline BP levels and the BP reduction after amlodipine therapy was begun. No BP reduction > 10 mm Hg was observed when the baseline systolic/diastolic BP was < 120/70 mm Hg. Multiple linear regression analysis disclosed that the nighttime BP reduction afforded by amlodipine was dependent on the baseline nighttime BP levels, but not on the baseline nocturnal fall of BP. Once-daily use of amlodipine reduced BP levels throughout the day and night in hypertensive patients who show minimal or mild nocturnal BP fall, but it had no effects on nocturnal BP in those who show a substantial nighttime BP reduction. Thus, when we controlled using daytime office BP, amlodipine might not further reduce nocturnal BP to the extent that it accelerates the brain ischemia in some hypertensive patients with marked nocturnal BP reduction.     

Nocturnal blood pressure patterns and cardiovascular outcomes in patients with masked hypertension

Masked hypertension (MHT) is characterized by normal clinic and above normal 24‐hour ambulatory blood pressure (BP) levels. We evaluated clinical characteristics and CV outcomes of different nocturnal patterns of MHT. We analyzed data derived from a large cohort of adult individuals, who consecutively underwent home, clinic, and ambulatory BP monitoring at our Hypertension Unit between January 2007 and December 2016. MHT was defined as clinic BP <140/90 mm Hg and 24‐hour BP ≥ 130/80 mm Hg, and stratified into three groups according to dipping status: (a) dippers, (b) nondippers, and (c) reverse dippers. From an overall sample of 6695 individuals, we selected 2628 (46.2%) adult untreated individuals, among whom 153 (5.0%) had MHT. In this group, 67 (43.8%) were nondippers, 65 (42.5%) dippers, and 21 (13.7%) reverse dippers. No significant differences were found among groups regarding demographics, clinical characteristics, and prevalence of risk factors, excluding older age in reverse dippers compared to other groups (P < 0.001). Systolic BP levels were significantly higher in reverse dippers than in other groups at both 24‐hour (135.6 ± 8.5 vs 130.4 ± 6.0 vs 128.2 ± 6.8 mm Hg, respectively; P < 0.001) and nighttime periods (138.2 ± 9.1 vs 125.0 ± 6.3 vs 114.5 ± 7.7 mm Hg; P < 0.001). Reverse dipping was associated with a significantly higher risk of stroke, even after correction for age, gender, BMI, dyslipidemia, and diabetes (OR 18.660; 95% IC [1.056‐33.813]; P = 0.046). MHT with reverse dipping status was associated with higher burden of BP and relatively high risk of stroke compared to both dipping and nondipping profiles, although a limited number of CV outcomes have been recorded during the follow‐up.     

Age-Related Differences in the Mechanism of Nondipping Among Patients with Obstructive Sleep Apnea Syndrome

The frequency of nondipper (those lacking the normal drop in nocturnal blood pressure [BP]) is high in patients with obstructive sleep apnea syndrome (OSAS). The objective of this study is to investigate age-related differences in the nocturnal BP profile of patients with OSAS. The study subjects included 214 patients with polysomnography-diagnosed OSAS. The status of dipper or nondipper was determined by 24-hour ambulatory BP measurements. We divided the subjects into three groups by age (younger, middle-aged, and elderly) and compared the frequency and sleep profiles of nondippers in the different age groups. The prevalence of nondippers was significantly higher in the elderly OSAS group than in the younger and middle-aged OSAS groups (69% vs. 45%, 47%; P < .05). In the younger OSAS group, nondippers, when compared with dippers, were characterized by higher apnea–hypopnea index (AHI, 48.2 ± 27.1 vs. 37.4 ± 23.0 times/h, P < .05), whereas in the middle-aged and elderly OSAS groups, the AHI of nondippers was almost identical to that of dippers. On the other hand, in the elderly OSAS group, nondippers, when compared with dippers, had shorter periods of slow wave sleep as measured by nonrapid eye movement stage 3–4, whereas nondippers and dippers in the other two age groups were not different in terms of slow wave sleep. These results indicate age-related differences in major mechanisms leading to nondipping. Severe apnea causes nondipping only in young OSAS patients, whereas disturbance of sleep quality plays a more important role in elderly OSAS patients.     

Impact of abnormal nocturnal blood pressure fall on vascular function

BACKGROUND: It is well known that nondipping pattern of arterial hypertension has a harmful effect on target organs such as the brain, heart, and kidneys. However, it remains uncertain whether abnormal dipping patterns of nocturnal blood pressure (BP), such as extreme and reverse dipping, influence vascular function. METHODS: This study comprised consecutive 2800 individuals (1554 men and 1246 women). All were nondiabetic and had uncomplicated, untreated essential sustained hypertension based on office measurements. After a 2-week wash-out period, 24-h ambulatory BP recordings were obtained and patients were classified by their nocturnal systolic BP fall (132 extreme dippers with >20% nocturnal systolic BP fall; 1235 dippers with >10% but <20% fall; 1146 nondippers with >0% but <10% fall; and 287 reverse dippers with <0% fall). Microalbumin, ACR (albumin/creatinine ratio), and microglobulin values were measured in all groups. RESULTS: Extreme dippers did not differ from dippers with regard to microalbumin, microglobulin excretion, or ACR. On the contrary, reverse dippers had significantly (P <.0001) higher values, compared with nondippers, for microalbumin (49.5 v 37.2 mg/dL), microglobulin (10.33 v 8.71 mg/dL), ACR (104.9 v 65.2), and percentages of abnormal values for these parameters. CONCLUSIONS: Microalbuminuria, an index of vascular function, differentiates reverse dippers from nondippers, but not extreme dippers from dippers among hypertensive patients.     

Nocturnal dipping status and the association of morning blood pressure surge with subclinical target organ damage in untreated hypertensives

The authors aimed to investigate the association between sleep‐through morning surge (MS) in blood pressure (BP) and subclinical target organ damage in untreated hypertensives with different nocturnal dipping status. This cross‐sectional study included 1252 individuals who underwent anthropometric measurements, serum biochemistry evaluation, 24‐hour ambulatory blood pressure monitoring, echocardiography, and carotid ultrasonography. Left ventricular mass index, left atrial dimension, and carotid intima‐media thickness were evaluated. Participants were grouped according to nocturnal systolic BP dipping rate (388 dippers, 10%‐20%; 674 non‐dippers, 0%‐10%; 190 reverse dippers, <0%). Twenty‐two extreme dippers were excluded. While reverse dippers exhibited the most severe signs of damage, only dippers showed significant and positive correlation between MS and hypertension‐mediated organ damage (all P < .05), with significant area under the receiver operating characteristic curve for discriminating left ventricular hypertrophy (0.662), left atrial enlargement (0.604), and carotid intima‐media thickening (left, 0.758; right, 0.726; all P < .05). MS showed significant association with subclinical organ damage on both logistic and multiple linear regression analysis adjusted for age, sex, body mass index, smoking status, and alcohol consumption status, as well as for the levels of fasting blood glucose, uric acid, serum creatinine, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol, even when 24‐hour, daytime, nocturnal, and morning systolic BP were included (odds ratio >1 and P < .01 for all types of damage). Besides race, nocturnal dipping status might affect the role of MS in subclinical target organ damage, with a significant association only in dippers, independent of other systolic BP parameters. Dipping status might account for the discrepancies across previous reports.     

The changes in blood pressure after acute stroke: abolishing the ‘white coat effect’ with 24-h ambulatory monitoring

Objectives . To assess the changes in 24-h and casual blood pressure (BP) levels following hospitalization for acute stroke. Design . Prospective study of patients admitted with acute hemispheric stroke and hospitalized controls using casual and 24-h BP monitoring. Setting . Medical wards in a large teaching hospital. Subjects . Thirty-three patients (median age 77 years, 17 male) and 21 control subjects admitted non-acutely. Interventions . All subjects underwent 24-h BP monitoring within 24 h of stroke onset (patients) or admission (controls) and again at 1 week. Casual BPs were recorded over the same period. Main outcome measures . The change in BP over the first week in each group. Eleven stroke subjects had 24-h BP monitoring repeated at 6 months. Results . In the stroke group, 24-h systolic BP (SBP) fell by 7 mmHg (95% CI, 0 to 14 mmHg; P < 0.05) and diastolic BP (DBP) by 3 mmHg (95% CI, 0 to 6 mmHg; P < 0.02) over the first week. Mean 24-h BP levels in the control group did not change during this period. However, casual BP recordings fell in both stroke (18/12 mmHg) and control (19/9 mmHg) groups. Stroke subjects followed to 6 months showed no further change in 24-h BP (day 7: 137±17/79±13 mmHg; month 6: 138 ± 16/78 ± 11 mmHg). Conclusions . Although there was a large fall in causal BPs seen in both groups there, was only a small, but a significant fall in mean 24-h BP over the first week following hemispheric stroke that was not seen in control subjects. Although the ‘white coat effect’ and admission to hospital play an important part in the high casual BP observed in the days following acute stroke they are unlikely to be the sole factors.     

Is HOMA index a predictor of nocturnal nondipping in hypertensives with newly diagnosed type 2 diabetes mellitus?

OBJECTIVE: Insulin resistance is involved in glucose intolerance, type 2 diabetes mellitus and hypertension. We aimed to analyze relationship between insulin resistance and nocturnal nondipping. METHODS: Patients underwent physical and biochemical evaluation, clinic and ambulatory blood pressure measurements. The homeostasis model assessment (HOMA) index was calculated. RESULTS: Ninety-six essential hypertensive patients, of whom 42 were dippers, with newly diagnosed type 2 diabetes mellitus were included. Nighttime average heart rate and mean arterial pressure of nondippers were higher than dippers (P<0.0001 and 0.001). Nondippers had higher fasting plasma glucose, serum insulin levels and HOMA indices than dipper patients (P=0.006, <0.0001 and <0.0001). Ten dippers and 36 nondippers were insulin resistant (P<0.0001). Clinic (r=+0.22, P=0.031), daytime average (r=+0.27, P=0.007), nighttime average (r=+0.33, P=0.001), 24-h average systolic (r=+0.25, P=0.015) and nighttime average diastolic blood pressures (r=+0.31, P=0.002) were positively correlated with homeostasis model assessment index. Nighttime mean arterial pressure and heart rates (daytime, nighttime, 24-h average) showed positive correlation with homeostasis model assessment index. In multivariate analysis, high homeostasis model assessment index was associated with increased nondipping risk (odds ratio: 1.85, confidence interval: 1.24-2.76, P=0.003). After adjustment of several factors, average nighttime systolic (P<0.0001), diastolic (P<0.0001) and 24-h diastolic blood pressure (P=0.029) and heart rate (P=0.001) measurements of insulin resistant patients were higher than nonresistant patients. CONCLUSIONS: Insulin resistance is related with diurnal blood pressure variation. The HOMA index may be a predictor of nocturnal nondipping in patients with essential hypertension and newly diagnosed type 2 diabetes mellitus.     

Metformin attenuates the postprandial fall in blood pressure in type 2 diabetes

Metformin has been shown to modulate the cardiovascular response to intraduodenal glucose in patients with type 2 diabetes (T2DM), and may have the capacity to regulate postprandial blood pressure (BP), which is often inadequately compensated in T2DM, resulting in postprandial hypotension. In the present study, we evaluated the acute effects of metformin on the BP and heart rate (HR) responses to oral glucose in patients with T2DM. Ten diet-controlled T2DM patients were evaluated on two occasions in a double-blind, randomized, crossover design. Participants received either metformin 1 g or saline (control) intraduodenally 60 minutes before ingesting a 50 g glucose drink labelled with 150 mg ¹³C-acetate. BP, HR, plasma glucagon-like peptide-1 (GLP-1) and gastric emptying (breath test) were evaluated over 180 minutes. Systolic and diastolic BP decreased and HR increased after oral glucose (P < 0.001 for all) on both days. Metformin attenuated the fall in systolic BP (P < 0.001), increased plasma GLP-1 concentrations (P < 0.05) and slowed gastric emptying (P < 0.05) without significantly affecting diastolic BP or HR. In conclusion, metformin acutely attenuates the hypotensive response to oral glucose, associated with augmented GLP-1 secretion and delayed gastric emptying, effects potentially relevant to its favourable cardiovascular profile.     

Sequelae of Acute Hypoglycaemia on 24 hour Blood Pressure and Metabolic Parameters in Normal and Type 1 (Insulin-dependent) Diabetic Individuals

This study was performed to assess possible delayed after-effects of acute hypoglycaemia on blood pressure (BP) and heart rate (HR) over a 24-h period. Eleven insulin-dependent diabetic patients and 11 sex, age, and body mass index matched non-diabetic subjects were studied. Blood pressure was measured using a non-invasive ambulatory blood pressure monitor following acutely induced hypoglycaemia in the morning. No significant differences were observed in 24-h systolic and diastolic BP and HR in either groups, between the day when hypoglycaemia was induced and the day when plasma glucose was kept normal. In diabetic patients, hypoglycaemia induced a temporary but significant fall in mean BP (-7 ± 1 mmHg vs -2 ± 2; p < 0.05). Plasma glucose levels were significantly higher in insulin-dependent diabetic patients following hypoglycaemia than in those observed during the reference test. This study demonstrates that acute hypoglycaemia in insulin-dependent diabetic subjects does not cause significant alterations in 24-h BP in either diabetic or normal subjects.