ABSTRACT—Diabetes may develop in nondiabetic hypertensive subjects during treatment, but the long-term cardiovascular implications of this phenomenon are not clear. We determined the prognostic value ...of new diabetes in hypertensive subjects. In a long-term cohort study, 795 initially untreated hypertensive subjects, 6.5% of whom with type 2 diabetes, underwent diagnostic procedures including 24-hour ambulatory blood pressure (BP) monitoring and electrocardiography (ECG). Procedures were repeated after a median of 3.1 years in the absence of cardiovascular events. Follow-up duration was 1 to 16 years (median 6.0). New diabetes occurred in 5.8% of subjects initially without diabetes. Antihypertensive treatment included a diuretic in 53.5% of these subjects, versus 30.4% of those in whom diabetes did not develop (P =0.002). Plasma glucose at entry (P =0.0001) and diuretic treatment on follow-up (P =0.004) were independent predictors of new diabetes. Subsequent to the follow-up visit, a first cardiovascular event occurred in 63 subjects. Event rate in nondiabetic subjects at both visits, new diabetes, and diabetes at entry were 0.97, 3.90, and 4.70×100 person-years, respectively (P =0.0001). After adjustment for several confounders, including 24-hour ambulatory BP, the relative risk of events was 2.92 (95% CI1.33 to 6.41; P =0.007) in the group with new diabetes and 3.57 (95% CI1.65 to 7.73; P =0.001) in the group with previous diabetes, when compared with the group persistently free of diabetes. In treated hypertensive subjects, occurrence of new diabetes portends a risk for subsequent cardiovascular disease that is not dissimilar from that of previously known diabetes.
Sleep deprivation induced by cuff inflations during overnight blood pressure (BP) monitoring might interfere with the prognostic significance of nighttime BP. In 2934 initially untreated hypertensive ...subjects, we assessed the perceived quantity of sleep during overnight BP monitoring. Overall, 58.7%, 27.7%, 9.7%, and 4.0% of subjects reported a sleep duration perceived as usual (group A), <2 hours less than usual (group B), 2 to 4 hours less than usual (group C), and >4 hours less than usual (group D). Daytime BP did not differ across the groups (all Ps not significant). Nighttime BP increased from group A to D (124/75, 126/76, 128/77, and 129/79 mm Hg, respectively; all Ps for trend <0.01). Over a median follow-up period of 7 years there were 356 major cardiovascular events and 176 all-cause deaths. Incidence of total cardiovascular events and deaths was higher in the subjects with a night/day ratio in systolic BP >10% compared with those with a greater day–night BP drop in the group with perceived sleep duration as usual or <2 hours less than usual (both P<0.01), not in the group with duration of sleep ≥2 hours less than usual (all Ps not significant). In a Cox model, the independent prognostic value of nighttime BP for total cardiovascular end points and all-cause mortality disappeared in the subjects with perceived sleep deprivation ≥2 hours. In conclusion, nighttime BP rises and loses its prognostic significance in the hypertensive subjects who perceive a sleep deprivation by ≥2 hours during overnight monitoring.
It is uncertain whether left ventricular hypertrophy (LVH) confers an increased risk for cerebrovascular disease in apparently healthy patients with essential hypertension.
A total of 2363 initially ...untreated hypertensive patients (mean age 51+/-12 years, 47% women) free of previous cardiovascular disease were followed up for up to 14 years (mean 5 years). At entry, all patients underwent diagnostic tests, including ECG, echocardiography, and 24-hour ambulatory blood pressure (BP) monitoring. At entry, the prevalence of LVH was 17.6% by ECG (Perugia score) and 23.7% by echocardiography (LVM >125 g/m(2)). Over the subsequent years, 105 patients experienced a first stroke or transient ischemic attack. The cerebrovascular event rate was higher among patients with LVH at entry, diagnosed by either ECG or echocardiography, than among those without hypertrophy (both P<0.01). After control for the significant influence of age, sex, diabetes, and 24-hour mean ambulatory BP, LVH by ECG conferred an increased risk for cerebrovascular events (relative risk RR 1.79; 95% CI 1.17 to 2.76). LVH by echocardiography also conferred a higher risk for cerebrovascular events (RR 1.64; 95% CI 1.07 to 2.68). For each increase in LV mass of 1 SD (29 g/m(2)), there was a significant independent increase in the risk for cerebrovascular events (RR 1.31; 95% CI 1.09 to 1.58).
In apparently healthy patients with essential hypertension, LVH diagnosed by ECG or echocardiography confers an excess risk for stroke and transient ischemic attack independently of BP and other individual risk factors.
Increased left ventricular (LV) mass predicts an adverse outcome in patients with essential hypertension. The purpose of this study was to determine the relation between changes in LV mass during ...antihypertensive treatment and subsequent prognosis.
Procedures including echocardiography and 24-hour ambulatory blood pressure (BP) monitoring were performed in 430 patients with essential hypertension before therapy and after 1217 patient-years. Months or years after the follow-up visit, 31 patients suffered a first cardiovascular morbid event. The patients with a decrease in LV mass from the baseline to follow-up visit were compared with those with an increase in LV mass. There were 15 events (1.78 per 100 person-years) in the group with a decrease in LV mass and 16 events (3.03 per 100 person-years) in the group with an increase in LV mass (P=.029). In a Cox model, the lesser cardiovascular risk in the group with a decrease in LV mass (hazard ratio HR, 0.46; 95% CI, 0.22 to 0.99) remained significant (P=.04) after adjustment for age (HR, 1.06; 95% CI, 1.03 to 1.10; P=.0008) and baseline LVH at ECG (HR, 3.85; 95% CI, 1.52 to 9.78; P=.012). In that model, baseline LV mass bordered on statistical significance (HR, 1.01; 95% CI, 1.00 to 1.03; P=.06). In the subset with LV mass > 125 g/m2 at the baseline visit (26% of subjects), the event rate was lower among the subjects who achieved regression of LVH than in those who did not (1.58 versus 6.27 events per 100 person-years; P=.002). This difference held in the multivariate analysis (HR, 0.18; 95% CI, 0.05 to 0.68).
In essential hypertension, a reduction in LV mass during treatment is a favorable prognostic marker that predicts a lesser risk for subsequent cardiovascular morbid events. Such an association is independent of baseline LV mass, baseline clinic and ambulatory BP, and degree of BP reduction.
It is unclear whether insulin and insulin-like growth factor-1 (IGF-1) are independent determinants of left ventricular (LV) mass in essential hypertension.
We studied 101 never-treated nondiabetic ...subjects with essential hypertension. All had 24-hour noninvasive ambulatory blood pressure (ABP) monitoring and a 75-g oral glucose tolerance test. We determined fasting glucose, insulin, and IGF-1 and postload glucose and insulin 2 hours after glucose. Insulin resistance was estimated by the homeostasis model assessment (HOMA(IR)) formula. LV mass showed an association with body mass index (BMI) (r=0.47; P<0.01), postload insulin (r=0.54; P<0.01), HOMA(IR) (r=0.39; P<0.01), and IGF-1 (r=0. 43; P<0.01) and a weaker association with average 24-hour systolic and diastolic ABPs (r=0.29 and r=0.26; P<0.05) and basal insulin (r=0.31; P<0.05). Relative wall thickness was positively related to IGF-1 (r=0.39; P<0.01) but not to fasting or 2-hour postload insulin, HOMA(IR), and glucose. In a multiple regression analysis, the final LV mass model (R(2)=0.64) included IGF-1, postload insulin, average 24-hour systolic ABP, sex, and BMI. IGF-1 and postload insulin accounted for >40% of variability of LV mass. The final model (R(2)=0.36) for relative wall thickness included IGF-1 (16% total explained variability), average 24-hour systolic ABP, sex, BMI, and age but not insulin and HOMA(IR).
These data indicate that insulin and IGF-1 are powerful independent determinants of LV mass and geometry in untreated subjects with essential hypertension and normal glucose tolerance.
Objectives. We tested the prognostic value of a new electrocardiographic (ECG) method (Perugia score) for diagnosis of left ventricular hypertrophy (LVH) in essential hypertension and compared it ...with five standard methods (Cornell voltage, Framingham criterion, Romhilt-Estes point score, left ventricular strain, Sokolow-Lyon voltage).
Background. Several standard ECG methods for assessment of LVH are used in the clinical setting, but a comparative prognostic assessment is lacking.
Methods. A total of 1,717 white hypertensive subjects (mean age 52 years; 51% men) were prospectively followed up for up to 10 years (mean 3.3).
Results. At entry, the prevalence of LVH was 17.8% (Perugia score), 9.1% (Cornell), 3.9% (Framingham), 5.2% (Romhilt-Estes), 6.4% (strain) and 13.1% (Sokolow-Lyon). During follow-up there were 159 major cardiovascular morbid events (33 fatal). The event rate was higher in the subjects with than in those without LVH (all p < 0.001) according to all methods except the Sokolow-Lyon method. By multivariate analysis, an independent association between LVH and cardiovascular disease risk was maintained by the Perugia score (hazard ratio HR 2.04, 95% confidence interval CI 1.5 to 2.8) and the Framingham (HR 1.91, 95% CI 1.1 to 3.2), Romhilt-Estes (HR 2.63, 95% CI 1.7 to 4.1) and strain methods (HR 2.11, 95% CI 1.4 to 3.2). The Perugia score showed the highest population-attributable risk for cardiovascular events, accounting for 15.6% of all cases, whereas the Framingham, Romhilt-Estes and strain methods accounted for 3.0%, 7.4% and 6.8% of all events, respectively. LVH diagnosed by the Perugia score was also associated with an increased risk of cardiovascular mortality (HR 4.21, 95% CI 2.1 to 8.7), with a population-attributable risk of 37.0%.
Conclusions. The Perugia score carried the highest population-attributable risk for cardiovascular morbidity and mortality compared with classic methods for detection of LVH. Traditional interpretation of standard electrocardiography maintains an important role for cardiovascular risk stratification in essential hypertension.
Prognostic Significance of the White Coat Effect Verdecchia, Paolo; Schillaci, Giuseppe; Borgioni, Claudia ...
Hypertension (Dallas, Tex. 1979),
1997-June, Letnik:
29, Številka:
6
Journal Article
Recenzirano
The difference between clinic and ambulatory blood pressure (BP) has been used to quantify the pressure reactivity to the doctor's visit (white coat effect). We investigated the prognostic ...significance of the clinic-ambulatory BP difference in the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study. A total of 1522 subjects contributed 6371 person-years of observation. All subjects had an initial off-therapy diagnostic workup including 24-hour noninvasive ambulatory BP monitoring. The predicted values of ambulatory BP progressively diverged from the identity line (white coat effect of 0 mm Hg) with increasing clinic BP, but the predicted values of clinic BP tended toward the identity line with increasing ambulatory BP. Hence, the clinic-ambulatory BP difference showed a direct association with clinic BP and an inverse association with ambulatory BP. Consequently, a high clinic-ambulatory BP difference predicted both a high clinic and a low ambulatory BP, whereas a low clinic-ambulatory BP difference predicted both a low clinic and a high ambulatory BP. The clinic-ambulatory BP difference showed also a direct association with age. During up to 9 years of follow-up (mean, 4.2 years), there were 157 major cardiovascular morbid events (125 nonfatal and 32 fatal). The rate of total cardiovascular morbid events did not differ (log-rank test) among the four quartiles of the distribution of the clinic-ambulatory BP difference (2.13, 2.92, 2.10, and 2.83 events per 100 patient-years for systolic BP and 2.94, 2.14, 2.58, and 2.16 events per 100 patient-years for diastolic BP). Also, the rate of fatal cardiovascular events did not differ among the four quartiles of the distribution of the clinic-ambulatory BP difference. The clinic-ambulatory BP difference, taken as a measure of the white coat effect, does not predict cardiovascular morbidity and mortality in subjects with essential hypertension. (Hypertension. 1997;29:1218-1224.)
The mechanisms underlying the increased cardiovascular risk after menopause are incompletely known. To investigate whether menopause may induce left ventricular structural and functional adaptations ...in normotensive and hypertensive women, we compared in a case-control setting (1) 76 untreated hypertensive premenopausal women with 76 postmenopausal women and (2) 30 normotensive premenopausal women with 30 postmenopausal women. Subjects were individually matched by age (+/- 5 years; range, 45 to 55), clinic systolic blood pressure (+/- 5 mm Hg), and body mass index (+/- 2 kgxm). All subjects underwent 24-hour blood pressure monitoring and M-mode echocardiography. Age, clinic and daytime blood pressure, body mass index, and smoking habits did not differ between the paired groups. After menopause, blood pressure fall from day to night was lower in both normotensives (10/15% versus 16/21%) and hypertensives (12/17% versus 16/21%) (all P<0.01). Menopause was also associated with a greater left ventricular relative wall thickness (38.8% versus 35.1% in normotensives, 40.2% versus 37.5% in hypertensives) and a reduced midwall fractional shortening (17.3% versus 18.6% in normotensives, 16.6% versus 17.9% in hypertensives) (all P<0.05). We conclude that menopause is associated with blunted day-night blood pressure reduction, impaired left ventricular systolic performance, and concentric left ventricular geometric pattern. These finding are independent of presence or absence of high blood pressure. (Hypertension. 1998;32:764-769.)
The rise in blood pressure (BP) associated with clinical visit (white coat effect) may be one basic mechanism of white coat hypertension (persistently raised clinic BP together with a normal BP ...outside the clinic), but the relations between white coat hypertension, white coat effect, and target organ damage have not yet been assessed on large populations. Thus, we performed 24-h noninvasive ambulatory BP monitoring and 2D-guided M-mode echocardiography in 1,333 untreated subjects with essential hypertension and 178 control normotensive subjects. White coat hypertension was defined by an average daytime ambulatory BP < 131/86 mm Hg in women and < 136/87 mm Hg in men and its prevalence was 18.9% (n = 252). The white coat effect was calculated for systolic and diastolic BP as the difference between clinic BP and average daytime ambulatory BP. Echocardiographic left ventricular mass was slightly but not significantly greater in the group with white coat hypertension than in the normotensive group (93
v 87 g/m
2,
P = NS), and increased in the group with ambulatory hypertension (112 g/m
2,
P < .01). The prevalence of white coat hypertension markedly decreased from the first to the fourth Joint National Committee V (JNC V) stage of severity of hypertension (186/559 subjects (33%) in I; 59/501 (11%) in II 7/230 (3%) in III; 0/43 (0%) in IV;
P < .001). The magnitude of the white coat effect, which was greater (all
P < .01) in the group with white coat hypertension (19.7/12.5 mm Hg) than in that with ambulatory hypertension (12.5/4.2 mm Hg), increased with the JNC V stage (7/4 mm Hg in I, 16/6 mm Hg in II, 23/8 mm Hg in III, 29/12 mm Hg in IV). Furthermore, the magnitude of the white coat effect did not show any association with echocardiographic LV mass, both in the group with white coat hypertension (r = −0.02/-0.06) and in that with ambulatory hypertension (r = 0.008/−0.05). We conclude that the magnitude of the white coat effect, expressed as the difference between clinic BP and daytime ambulatory BP, may not be a clinically relevant finding, failing to reflect the severity of hypertension and the degree of associated left ventricular structural changes. The actual levels of ambulatory BP, rather than the magnitude of white coat effect, should then be used to identify the subjects with normal BP outside the clinic and potentially low cardiovascular risk.
BACKGROUNDPrevious studies revealed a direct association between resting heart rate and risk of mortality in essential hypertension. However, resting heart rate is a highly variable measure since it ...is affected by the alerting reaction to the visit.
OBJECTIVETo investigate whether the heart rate values recorded during the 24 h of ambulatory blood pressure monitoring are independent predictors of survival of uncomplicated subjects with essential hypertension.
METHODSWe followed up 1942 initially untreated and uncomplicated subjects with essential hypertension (mean age 51.7 years, 52% men) for an average of 3.6 years (range 0–10 years). All subjects underwent baseline procedures including 24 h non-invasive blood pressure monitoring with simultaneous assessment of heart rate, one reading every 15 min for 24 h.
MAIN OUTCOME MEASURESAll-cause mortality and cardiovascular morbidity.
RESULTSDuring follow-up there were 74 deaths from all causes (1.06 per 100 person-years) and 182 total (fatal plus non-fatal) cardiovascular morbid events (2.66 per 100 person-years). Clinic, average 24 h, daytime and night-time heart rates exhibited no association with total mortality. However, the subjects who subsequently died had had a blunted reduction of heart rate on going from day to night during the baseline examination. After adjustment for age (P < 0.001), diabetes (P < 0.001) and average 24 h systolic blood pressure (SBP, P = 0.002) in a Cox model, for each 10% less reduction in the heart rate from day to night the relative risk of mortality was 1.30 (95% confidence interval 1.02-1.65, P = 0.04). Rates of death were 0.38, 0.71, 0.94 and 2.0 per 100 person years among subjects in the four quartiles of the distribution of the percentage reduction in heart rate from day to night. The baseline day-night changes in the heart rate exhibited an inverse correlation to age and to clinic and ambulatory SBP and a direct association with the day-night changes in blood pressure. The degree of reduction of heart rate from day to night also had an independent inverse association with total cardiovascular morbidity after adjustment for age, diabetes and left ventricular hypertrophy, but this association did not remain significant when average 24 h SBP and the degree of day-night reduction in SBP were entered into the equation.
CONCLUSIONSA flattened diurnal rhythm of heart rate in uncomplicated subjects with essential hypertension is a marker of risk for subsequent all-cause mortality and this association persists after adjustment for several risk factors. For assessing these subjects, a limited and uniformly distributed period of ambulatory heart rate recording during the 24 h is clinically valuable.
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