Seasonal variation in haemodynamics and blood pressure ... - Nature

Journal of Human Hypertension (2010) 24, 410–416 & 2010 Macmillan Publishers Limited All rights reserved 0950-9240/10 $32.00 www.nature.com/jhh

ORIGINAL ARTICLE

Seasonal variation in haemodynamics and blood pressure-regulating hormones KJ Radke1,2 and JL Izzo Jr1 1

Department of Medicine, Erie County Medical Center, Buffalo, NY, USA and 2School of Nursing, and Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA

Seasonal variation in blood pressure (BP) has been described in some people, although the variation is small for both systolic and diastolic BPs. The aim of this study was to elucidate underlying haemodynamic and hormonal mechanisms that may occur to defend seasonal changes in BP. Participants were 27 men and 7 women with either normal BP or early hypertension. Measurements of haemodynamics (cardiac output by dual-gas rebreathing) and hormones (resting catecholamines, renin activity, and aldosterone by radioenzymatic assay or radioimmunoassay) were performed during the summer, fall, winter, and spring seasons. Student’s paired t-test with Bonferroni modification and regression analyses were used to examine the data with a significance level of Po0.05. Systolic and diastolic BP remained relatively constant across seasons. Cardiac output and stroke volume significantly decreased

10 and 15%, respectively, from summer to winter, whereas heart rate and systemic vascular resistance significantly increased 5 and 11%, respectively. Plasma aldosterone (PA) significantly increased 59% from summer to winter, whereas plasma norepinephrine (PNE), plasma epinephrine, and plasma renin activity (PRA) increased 19, 2, and 17%, respectively (pNS for each). Across the four seasons, mean arterial pressure significantly correlated with PRA and PA, whereas systemic vascular resistance significantly correlated with PNE and PRA. There are dramatic counterregulatory haemodynamic and hormonal adaptations to maintain a relatively constant BP. Norepinephrine, PRA, and aldosterone have a function in mediating the changes in haemodynamics. Journal of Human Hypertension (2010) 24, 410–416; doi:10.1038/jhh.2009.75; published online 24 September 2009

Keywords: seasons; blood pressure; haemodynamics; norepinephrine; plasma renin activity; aldosterone

Introduction Seasonal variation in blood pressure (BP) has been shown for normotensive and hypertensive men and women, with systolic blood pressure (SBP) and diastolic blood pressure (DBP) being higher in winter than in summer.1–7 However, in these large studies the seasonal effects were small. Summer– winter differences for SBP ranged from 2 to 7 mm Hg and for DBP from 0.3 to 5 mm Hg under the condition of recumbency, sitting, standing, or 24-h ambulatory monitoring. There is also evidence that seasonal variation occurs for BP-regulating hormones such as plasma norepinephrine (PNE)8–10 and plasma epinephrine (PE),9,10 which are higher in winter than in summer. On the other hand, there is little information regarding seasonal effects on plasma renin activity Correspondence: Dr KJ Radke, Department of Medicine, Erie County Medical Center, 462 Grider Street, Buffalo, NY 14215, USA. E-mail: [email protected] Received 17 June 2009; revised 2 August 2009; accepted 4 August 2009; published online 24 September 2009

(PRA) and plasma aldosterone (PA). Hata et al.9 reported no seasonal variation in PRA, and the data for PA are controversial.9,11 Because the BP-regulating hormones have usually been studied as entities by themselves or in isolation from cardiovascular events except for BP, the temporal relationships between these hormones and haemodynamics across the four seasons are unclear. In addition, it is unknown as to the contribution of each hormone to maintain SBP and DBP fairly constant across the seasons. One purpose of our study was to examine the effects of seasonal adaptation on multiple cardiovascular events and BP-regulating hormones within the same study. Another purpose was to determine the haemodynamic and hormonal mechanisms that prevent marked changes in BP when challenged by seasonal differences in outside temperature. Moreover, we examined the independent contribution of several factors on mean arterial pressure (MAP), cardiac output (CO), and systemic vascular resistance (SVR). Preliminary data from this study were reported earlier for seasonal adaptation of haemodynamic

Seasonal haemodynamics and hormonal responses KJ Radke and JL Izzo Jr 411

events and plasma catecholamines in a combined sample of normotensive and early hypertensive subjects.8 Since then, we increased the sample size and now report all variables studied including PRA, PA, and urinary catecholamines. In addition, we have extended our analysis to determine seasonal outcomes in subgroups of normotensive and prehypertensive subjects, and to determine the effect of increased BP on seasonal adaptation of the haemodynamic and hormonal mechanisms.

Materials and methods The University Research Subjects Review Board approved this study that was conducted in accordance with the Declaration of Helsinki. Male and female subjects who had no known history of high BP were solicited by advertisement. All participants understood the protocol and gave their informed consent. A convenience sample of subjects included those with normal BP (p120/80 mm Hg) and those with early hypertension. Early hypertension was defined as a minimum of two documented occasions where clinic or office DBP readings were greater than 90 mm Hg but did not exceed 105 mm Hg in the sitting position. Subjects also met the following criteria: declined medical therapy if newly diagnosed with early hypertension; had no other active medical problems; and were not taking any cardiovascular drugs. Subject enrolment was staggered into four seasons: summer (July and August), fall (October and November), winter (January and February), and spring (April and May). Thus, it was a longitudinal study in which each subject was studied on four occasions. Subjects refrained from caffeine and nicotine after midnight of each study day, as instructed, except for two subjects who had coffee on one occasion. On each study day, subjects reported to the Outpatient Clinic during 0830 and 1200 a.m. with a few minor variations. Screening BPs (mercury sphygmomanometer with a cuff sized to the arm and using phases 1 and 5 of the Korotkoff sounds) and heart rates (HRs) (radial pulse for 1 min) were determined after 5 min of recumbency, 5 min of quiet sitting with the back unsupported, and 2 min of upright posture. Supine and sitting BPs were the means of three determinations, whereas upright BPs were the means of two determinations. HR was measured immediately after each BP was determined. After the BP and HR screening measures, height and weight were determined with weight being determined during each season. Subjects were then escorted to the Pulmonary Laboratory. With the subject in a supine position, electrocardiogram (EKG) leads were attached and an indwelling venous catheter, which had a heparin lock, was inserted into an antecubital vein. The subject rested, undisturbed, until 15 minutes had elapsed from the

time the indwelling venous catheter was inserted. Blood was then drawn through the indwelling venous catheter and allocated into appropriate tubes to determine levels of PNE, PE, PRA, PA, and plasma creatinine. After blood sampling was completed, the BP was taken. The subject then performed duplicate acetylene–helium rebreathing manoeuvres, with a 5-min rest between runs, for determination of CO. This was followed by another BP determination. HR was determined by EKG before and after each rebreathing manoeuvre. The means of two determinations for CO and BP and of four determinations for HR were used as the final values. During the summer and winter seasons, subjects collected their urine over a 24-h period that included the second urine of the first morning to the first urine of the second morning. Creatinine, sodium (Na þ ), potassium (K þ ), norepinephrine (NE,) and epinephrine (E) were measured. NE and E were determined by a modified radioenzymatic assay that has been well established in the author’s (JLI) laboratory.12 PRA was determined by a standard radioimmunoassay (Dupont Inc., Wilmington, DE, USA) with standards in agreement with those published by the manufacturer. PA was determined using the Coat-a-Count No-Extraction Aldosterone Radioimmunoassay kit (Diagnostic Products, Los Angeles, CA, USA) with standards in agreement with those published by the manufacturer. Creatinine and electrolytes were measured by autoanalyzer. In some instances, all measurements were not obtained. If a data point was missing, all data for that variable in that subject were omitted from further analysis. Summer was considered the reference point for comparison with any other season. The average of four weights for each subject was used to calculate body mass index (BMI; kg/m2).13 To classify subjects into subgroups of normotensives and prehypertensives, values across all four seasons were averaged for SBP and DBP, and the higher mean value of either SBP or DBP was used. According to the criteria from the JNC 7 Report,14 we defined normotension as SBP in the range of 0–119 mm Hg and DBP in the range of 0–79 mm Hg. Prehypertension was defined as SBP in the range of 120–139 mm Hg and DBP in the range of 80–89 mm Hg. Hypertension was defined as SBP 4139 mm Hg and DBP489 mm Hg. All individual values for MAP (n ¼ 136) were used to calculate the grand MAP. Data collected and compared for all four seasons were analysed using Student’s paired t-test with Bonferroni modification. Differences were considered significant at Po0.017. Data collected only in the summer and winter seasons were analysed using Student’s paired t-test. Differences were considered significant at Po0.05. For multiple regression analysis (MRA), Pearson’s correlations, and linear regression analysis (LRA), a significance level of Po0.05 was used. SPSS version 13.0 was used to Journal of Human Hypertension


analyse all data. Data are expressed as the means ±s.e.m.

Results Characteristics of the subjects are presented in Table 1. Seventy-nine per cent of all subjects were male, and 21% were female. The subjects were young to middle-aged adults. Ninety-four per cent of all subjects were Caucasian. The BMI was comparable among the three groups and within the range of overweight.13 Those with hypertension were not included as a subgroup because of the small sample size (n ¼ 3). According to the US National Weather Service, the monthly average temperatures ranged from 19.6 to 23.2 1C (summer), 2.7 to 8.4 1C (fall), 5.3 to 0.9 1C (winter), and 7.2 to 15.5 1C (spring). Seasonal effects on haemodynamics and BP-regulating hormones in all subjects are shown in Table 2. Cardiovascular and hormonal responses that changed significantly from the summer season were CO (winter), HR (fall, winter), stroke volume (SV; fall, winter), SVR (winter), and PA (fall, winter). SBP, DBP, MAP, PNE, PE, and PRA did not change significantly. The patterns of responses for these data are depicted in Figure 1. The peak response for HR, PE, and PRA occurred in the fall season and preceded the peak response for SVR, PNE, and PA that occurred in the winter season. The nadir for CO and SV occurred in the winter season. Similar patterns of responses occurred in both normotensive and prehypertensive subgroups of subjects (data not shown). Renal function in terms of creatinine clearance was comparable for summer and winter seasons in all subjects and in the subgroup of those with prehypertension (Table 3). In contrast, creatinine clearance was higher in winter than in summer in those with normotension. Urinary excretion of Na þ , K þ , NE, and E was similar for the two seasons in all subjects as well as in the subgroups of normotensive and prehypertensive subjects. Seasonal effects on haemodynamics and BPregulating hormones in a subgroup of 16 subjects matched on all variables are shown in Table 4. The data are similar to those found in all subjects (Table 2). A summary of MRA done on the subgroup of 16 subjects is presented in Table 5. For MRA we had the computer enter the order of variables. The R2adj for MAP, CO, and SVR was 0.327, 0.254, and 0.477, respectively. The model was significant for MAP (F6,57 ¼ 6.093, Po0.000), CO (F6,57 ¼ 4.581, Po0.001), and SVR (F6,57 ¼ 10.564, Po0.000). For MAP, age was the most important significant predictor with PE and PNE making smaller but significant independent contributions. Age and PE had a positive effect, whereas PNE had a negative effect on MAP. Age was also the variable most significantly correlated with MAP followed by PA Journal of Human Hypertension

Table 1 Demographics Subjects

All

Normotensive

Prehypertensive

N

34

13

18

Gender Male Female Age (yr)

27 7 40±2

12 1 34±2

13 5 43±3

Race Caucasian Asian Hispanic BMI (kg/m2)

32 1 1 26±1

12 1 0 26±1

17 0 1 27±1

Values for age and BMI (body mass index) are the means±s.e.m.

and PRA. Age had a positive association, whereas PA and PRA had a negative association with MAP. For CO, age was the most important significant predictor with PA making a slightly less significant contribution. Both age and PA had a negative effect on CO. Age was the variable most significantly associated with CO followed by BMI and PA. Age and PA had a negative association, whereas BMI had a positive association with CO. For SVR, age was the only significant predictor and had a positive effect. Age also showed the most significant correlation and was positive. PNE had a significant positive association, whereas PRA and BMI had negative associations with SVR. LRA of summer–winter differences in haemodynamics and BP-regulating hormones with the grand MAP are presented in Table 6. The LRA model was significant only for PE and PA. R2 ranged from 0.1 to 15.1%. PE and PA explained 13 and 15%, respectively, of the grand MAP. PE had a significant positive relationship, and PA had a significant negative relationship with the grand MAP.

Discussion We conducted a longitudinal study on the seasonal adaptation of haemodynamic and hormonal responses with subjects at rest in the supine position, in which purposeful stimulation of the sympathetic nervous system due to positional change or ambulation was absent. Our data show that seasonal changes did not affect SBP, DBP, or MAP in healthy young and middle-aged adults in the northern United States. In contrast, HR and SVR significantly increased 5 and 11%, respectively, whereas CO and SV significantly decreased 10 and 15%, respectively, from summer to winter. The neurohormones, PNE and PE, increased 19 and 2%, respectively, from summer to winter, although these changes were not significant. Hata et al.9 also found no significant changes in PNE in 14 normotensive subjects in the supine position but


Table 2 Seaasonal effects on haemodynamics and blood pressure-regulating hormones Variables

n

Summer

Fall

Winter

Spring

Systolic pressure (mm Hg) Diastolic pressure (mm Hg) Mean arterial pressure (mm Hg) Cardiac output (l min1) Heart rate (beats per min) Stroke volume (ml) Systemic vascular resistance (dyn s cm5) Plasma norepinephrine (pg ml1) Plasma epinephrine (pg ml1) Plasma renin activity (ng ml1 h1) Plasma aldosterone (pg ml1)

34 34 34 23 34 23 23 29 29 26 32

120±3 78±2 92±2 6.9±0.3 64±1 112±6 1112±61 232±19 48±3 1.26±0.16 68.2±6.6

119±2 78±1 92±1 6.5±0.3 68±2** 100±6* 1177±63 249±18 53±3 1.81±0.32 97.9±9.5*

120±2 78±2 92±2 6.2±0.2* 67±2* 95±6** 1234±61* 276±20 49±3 1.47±0.24 108.7±10.1**

117±2 76±2 90±2 6.8±0.3 65±2 107±7 1102±61 268±18 44±3 1.25±0.18 89.3±10.1

Values are the means ±s.e.m. *Po0.017 vs summer. **Po0.0017 vs summer.

did find a significant increase in PNE in 9 patients with untreated hypertension (DBP: 91–94 mm Hg). There was no seasonal effect on PE in the two groups. Owing to the small number of early hypertensives in our study, we did not analyse them as a separate group from the normotensive subjects. On the other hand, one group of investigators10 reported that PNE and PE were higher in winter than in summer in 10 healthy subjects who were studied in the supine position. BP was not reported. We found no seasonal effects on the 24-h urinary excretion of NE or E. Likewise, Johansson and Post15 reported no change in 24-h urinary excretion of NE. In contrast, other investigators4,9,16,17 found that 24-h urinary excretion of NE was higher in winter than in summer. Most investigators4,15–17 have reported no seasonal effect on 24-h urinary excretion of E. The discrepancy in plasma and urinary catecholamine results may be due to factors such as age, gender, use of caffeine, activity level, outside temperature, and study design. In regards to the renin–angiotensin–aldosterone system, PRA increased 17% from summer to winter, although this change was not significant. Likewise Hata et al.9 reported a nonsignificant change in PRA in both normotensive and untreated hypertensive groups. In contrast, PA significantly and profoundly increased 44% from summer to fall and 59% from summer to winter. Similarly, Nicolau et al.11 found that PA was significantly higher in fall and continued to remain higher in winter than in summer. On the other hand, Hata et al.9 reported no seasonal effect on PA. However, Hata et al.9 showed a higher urinary Na þ excretion in winter than in summer and attributed this to a higher Na þ intake. In our study, the increase in PA occurred without summer to winter changes in the urinary excretion of Na þ , reflecting that dietary intake of this nutrient was probably comparable for the two seasons. The role of PA is not as well understood as that of PNE, PE, and PRA relative to changes in haemodynamic parameters. However, the seasonal patterns for PNE, PRA, and PA suggest an important interplay of these hormones relative to SVR. PNE slightly

increased from summer to fall and continued with a small increase from fall to winter. The peak response in PRA occurred in the fall season and preceded the peak response of PA in the winter season. Although PRA decreased during the winter season, there may have been sufficient stimulus along with the small increase in PNE to drive the profound increase in PA. It has been reported that angiotensin II potentiates the vasoconstrictive effect of NE in normotensive and hypertensive male subjects.18 Moreover, both angiotensin II and NE are secretagogues for aldosterone biosynthesis.19 As the increase in SVR from summer to winter was accompanied by a profound increase in PA and because of the current interest in the effects of aldosterone on the vasculature,20–22 we were interested in determining the independent contribution of PA, as well as the other hormones, age, and BMI to MAP and its haemodynamic components, CO and SVR. Thus, we proceeded to do MRA in 16 subjects matched on all variables. Age was the best predictor for MAP followed by PE and PNE, whereas age and PA were the best predictors for CO. Age was the only significant predictor for SVR. All associations that were significant between haemodynamic and hormonal variables were weak. Only age showed a significant, moderate association, which occurred with MAP and SVR. The subjects in our study were either normotensive or early hypertensive. Thus, we were interested in determining the effect of increased BP on seasonal variation of the haemodynamic and hormonal variables, using LRA. Only PE and PA showed a significant relationship with the grand MAP. However, both correlations were less than 0.4 indicating weak associations. It seems, therefore, that increased BP blunts the seasonal variation of the haemodynamic and hormonal mechanisms. Our data show that the summer to winter decreases in CO and SV are proportional to the summer–winter increase in SVR, indicating a peripheral vasodilation in the summer season and a peripheral vasoconstriction in the winter season. This seasonal change in CO is the opposite of what Journal of Human Hypertension


Table 3 Seasonal effects on urinary electrolytes and catecholamines Variables

n

Summer

Winter

A. All subjects Creatinine clearance (l per 24 h) Urinary sodium (mEq per 24 h) Urinary potassium (mEq per 24 h) Urinary norepinephrine (mg per 24 h) Urinary epinephrine (mg per 24 h)

30 171±6 180±7 34 135±10 143±8 34 68±4 75±4 34 41±2 44±3 34 16±1 17±2

B. Normotensive subjects Creatinine clearance (l per 24 h) Urinary sodium (mEq per 24 h) Urinary potassium (mEq per 24 h) Urinary norepinephrine (mg per 24 h) Urinary epinephrine (mg per 24 h)

12 176±10 193±11* 13 145±20 131±10 13 63±7 71±6 13 37±4 42±6 13 17±2 19±2

C. Prehypertensive subjects Creatinine clearance (l per 24 h) Urinary sodium (mEq per 24 h) Urinary potassium (mEq per 24 h) Urinary norepinephrine (mg per 24 h) Urinary epinephrine (mg per 24 h)

15 168±10 174±9 18 131±13 156±12 18 72±5 79±5 18 41±3 43±4 18 16±2 16±2

Values are the means±s.e.m. *Po0.05.

Figure 1 Seasonal patterns for haemodynamic and hormonal responses. SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; CO, cardiac output; HR, heart rate; SV, stroke volume; SVR, systemic vascular resistance; PNE, plasma norepinephrine; PE, plasma epinephrine; PRA, plasma renin activity; PA, plasma aldosterone. Refer to Table 2 for means, s.e.m., and P values.

would have been predicted from the observed small wintertime increase in HR. However, because PNE and PRA were significantly associated with SVR, it is likely that seasonal adaptation intrinsically requires activation of the sympathetic nervous system that directly influences SVR as well as the renin–angiotensin–aldosterone system resulting in arterial and venous constriction. We recognize that the major limitation of our study is the relatively small sample size and therefore the potential problem of both type 1 and type 2 statistical errors. Thus, we recommend caution in Journal of Human Hypertension

generalizing or extrapolating our findings. This type of detailed haemodynamic profiling is difficult and expensive. However, the integrated picture we have shown provides unique insight into seasonal cardiovascular homeostasis. Further studies must be conducted to more fully understand the individual contributions of PNE, PRA, and PA on haemodynamics, particularly SVR, when challenged by a change in seasons. Moreover, studies need to be conducted to determine the sequence of dysregulatory cardiovascular and hormonal effects that occur during the prehypertension phase. Part of the normal seasonal adaptation process is increased sympathetic nervous system activation with an accompanying increase in SVR that is offset by an equivalent decrease in CO to maintain a constant BP. From these data, it seems that seasonal expansion and contraction of the cardiovascular system is blunted and that CO remains higher than normal throughout the year. This is consistent with the early hyperdynamic phases described in the Tecumseh, Michigan population.23 In conclusion, our results show a much wider range of adaptive changes in systemic haemodynamics and hormonal control mechanisms than would be predicted from BP alone, which remains quite constant over the four seasons. This constancy of BP is due to a decrease in CO from summer to winter that is counterregulated with an increase in SVR. Similar findings occurred in the subgroups of normotensive and prehypertensive subjects. In addition, we have provided evidence that PNE, PRA, and PA have a role in mediating the seasonal changes in haemodynamics, although such changes may be blunted by an increase in BP. On the basis of our finding that aldosterone was surprisingly 59%


Table 4 Seasonal effects on haemodynamics and blood pressure-regulating hormones in subjects matched on all variables Variables

Summer

Fall

Winter

Spring

Systolic pressure (mm Hg) Diastolic pressure (mm Hg) Mean arterial pressure (mm Hg) Cardiac output (l min1) Heart rate (beats per min) Stroke volume (ml) Systemic vascular resistance (dyn s cm5) Plasma norepinephrine (pg ml1) Plasma epinephrine (pg ml1) Plasma renin activity (ng ml1 h1) Plasma aldosterone (pg ml1)

116±5 74±3 88±3 7.3±0.4 62±2 120±8 998±65 207±18 51±4 1.37±0.2 79±10

117±4 76±3 90±3 6.9±0.3 67±2* 105±7** 1080±62* 215±20 53±6 2.25±0.48 129±14*

117±4 75±3 89±3 6.2±0.2* 65±2 98±7** 1173±67** 253±21 46±5 1.65±0.34 131±13*

114±4 73±2 87±3 6.7±0.4 63±2 109±10 1092±80 250±25 44±4 1.28±0.28 100±14

N ¼ 16. Values are the means±s.e.m. *Po0.017 vs summer. **Po0.0001 vs summer.

Table 5 Multiple regression analysis of mean arterial pressure, cardiac output and systemic vascular resistance Variables

t

b

P

R

A. Mean arterial pressure Plasma norepinephrine 0.279 2.135 0.037* 0.114 Plasma epinephrine 0.281 2.389 0.020* 0.147 Plasma renin activity 0.114 0.738 0.464 0.251 Plasma aldosterone 0.264 1.861 0.068 0.310 Age 0.636 4.943 0.000* 0.517 BMI 0.031 0.251 0.803 0.020

P

0.185 0.124 0.023* 0.006* 0.000* 0.439

B. Cardiac output Plasma norepinephrine 0.129 0.937 0.353 0.206 0.051 Plasma epinephrine 0.132 1.063 0.292 0.050 0.347 Plasma renin activity 0.041 0.256 0.799 0.058 0.325 Plasma aldosterone 0.325 2.183 0.033* 0.252 0.022* Age 0.360 2.661 0.010* 0.392 0.001* BMI 0.221 1.690 0.097 0.301 0.008* C. Systemic vascular resistance Plasma norepinephrine 0.052 0.451 0.654 0.262 0.018* Plasma epinephrine 0.060 0.575 0.568 0.049 0.349 Plasma renin activity 0.007 0.048 0.962 0.261 0.019* Plasma aldosterone 0.097 0.779 0.439 0.020 0.436 Age 0.710 6.264 0.000* 0.688 0.000* BMI 0.172 1.571 0.122 0.283 0.012*

this hormone in BP regulation and seasonal adaptation. Owing to the magnitude of changes we have observed, there are implications for the pathogenesis of hypertension, the interpretation of hormone levels, and perhaps even the decision to initiate or continue pharmacologic therapy.

What is known about topic K In clinical trials, it has been observed that blood pressures are slightly higher in winter than in summer, at least in some people. K Seasonal neurohormonal and haemodynamic adaptation has been described in small groups. What this study adds K From summer to winter, cardiac output uniformly decreases whereas systemic vascular resistance increases in reciprocal manner. For the most part these changes are matched, and the net effect on blood pressure is small. K Activity of the sympathetic nervous system and the renin– angiotensin–aldosterone system increases in winter, whereas the reverse pattern occurs during the summer. K The temporal relationships between haemodynamics and blood pressure-regulating hormones across the four seasons are shown.

Abbreviation: BMI, body mass index. N ¼ 64. *Po0.05.

Table 6 Linear regression analysis of summer–winter differences for haemodynamics and blood pressure-regulating hormones with the grand mean arterial pressure Variables

n

R2

R

t

P

Cardiac output Heart rate Stroke volume Plasma norepinephrine Plasma epinephrine Plasma renin activity Plasma aldosterone

32 34 32 33 33 26 32

0.081 0.028 0.036 0.001 0.129 0.032 0.151

0.284 0.166 0.190 0.027 0.359 0.178 0.388

1.625 0.954 1.057 0.151 2.142 0.886 2.306

0.115 0.347 0.299 0.881 0.040* 0.384 0.028*

Conflict of interest Dr Radke declares no conflict of interest. Dr Izzo has potential conflict of interest in that he has been funded by Novartis, GlaxcoSmithKline, and Daiichi/ Sankyo. Moreover, he has received compensation as a consultant and/or speaker for Merck, Medical Education Consultants, Novartis, GlaxoSmithKline, SCS Healthcare, Daiichi/Sankyo, and Medplan.

Grand MAP (n ¼ 136). *Po0.05.

Acknowledgements

higher in winter than in summer, it is imperative that future studies also include the use of aldosterone antagonists to further characterize the role of

We thank Pat Larrabee, MS, RN, project coordinator, and Wu, Yow-Wu, PhD, for statistical consultation. This study was supported, in part, by a grant from Journal of Human Hypertension


the New York State Affiliate of the American Heart Association.

References 1 Brennan PJ, Greenberg G, Miall WE, Thompson SG. Seasonal variation in arterial blood pressure. Br Med J 1982; 285: 919–923. 2 Khaw K, Barrett-Connor E, Suarez L. Seasonal and secular variation in blood pressure in man. J Card Rehabil 1984; 4: 440–444. 3 Kunesˇ J, Tremblay J, Bellavance F, Hamet P. Influence of environmental temperature on the blood pressure of hypertensive patients in Montreal. Am J Hypertens 1991; 4: 422–426. 4 Winnicki M, Canali C, Accurso V, Dorigatti F, Giovinazzo P, Palatini P. On behalf of the Harvest Study Group, Italy. Relation of 24-hour ambulatory blood pressure and short-term blood pressure variability to seasonal changes in environmental temperature in stage I hypertensive subjects. Clin Exp Hypertens 1996; 18: 995–1012. 5 Mundal R, Kjeldsen SE, Sandvik L, Erikssen G, Thaulow E, Erikssen J. Seasonal covariation in physical fitness and blood pressure at rest and during exercise in healthy middle-aged men. Blood Press 1997; 6: 269–273. 6 Sega R, Cesana G, Bombelli M, Grassi G, Stella ML, Zanchetti A et al. Seasonal variations in home and ambulatory blood pressure in the PAMELA population. J Hypertens 1998; 16: 1585–1592. 7 Madsen C, Nafstad P. Associations between environmental exposre and blood pressure among participants in the Oslo Health Study (HUBRO). Eur J Epidemiol 2006; 21: 485–491. 8 Izzo Jr JL, Larrabee PS, Sander E, Lillis LM. Hemodynamics of seasonal adaptation. Am J Hypertens 1990; 3: 405–407. 9 Hata T, Ogihara T, Maruyama A, Mikami H, Nakamaru M, Naka T et al. The seasonal variation of blood pressure in patients with essential hypertension. Clin Exp Hypertens 1982; A4: 341–354. 10 Kruse HJ, Wieczorek I, Hecker H, Creutzig A, Schellong SM. Seasonal variation of endothelin-1, angiotensin II, and plasma catecholamines and their relation to outside temperature. J Lab Clin Med 2002; 140: 236–241. 11 Nicolau GY, Haus E, Bogdan C, Plinga L, Robu E, Ungureanu E et al. Circannual rhythms of systolic and diastolic blood pressure in relation to plasma aldosterone and urinary norepinephrine in elderly

Journal of Human Hypertension

12 13

14

15 16

17

18

19 20

21

22 23

subjects and in children. Rev Roum Med Endocrinol 1986; 24: 97–107. Licht MR, Izzo Jr JL. Humoral effect of norepinephrine on renin release in humans. Am J Hypertens 1989; 2: 788–791. National Heart, Lung, and Blood Institute in cooperation with The National Institute of Diabetes and Digestive and Kidney Diseases. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. NIH Publication No. 98-4083, National Institutes of Health, September 1998. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA 2003; 289: 2560–2571. Johansson G, Post B. Catecholamine output of males and females over a one-year period. Acta Physiol Scand 1974; 92: 557–565. Lakatua DJ, Nicolau GY, Bogdan C, Plinga L, Jachimowicz A, Sackett-Lundeen L et al. Chronobiology of catecholamine excretion in different age groups. Prog Clin Bio Res 1987; 227B: 31–50. Tsuchihashi T, Uezono K, Abe I, Matsuoka M, Kawasaki T. Seasonal variation in 24-h blood pressure pattern of young normotensive women. Hypertens Res 1995; 18: 209–214. Reams GP, Bauer JH. Angiotensin II potentiates the vasoconstrictive effect of norepinephrine in normotensive and hypertensive man. J Clin Hypertens 1987; 3: 610–616. Williams GH. Aldosterone biosynthesis, regulation, and classical mechanism of action. Heart Fail Rev 2005; 10: 7–13. Wehling M, Spes CH, Win N, Janson CP, Schmidt BMW, Theisen K, Christ M. Rapid cardiovascular action of aldosterone in man. J Clin Endocrinol Metab 1998; 83: 3517–3522. Schmidt BMW, Montealegre A, Janson CP, Martin N, Stein-Kemmesies C, Scherhag A et al. Short term cardiovascular effects of aldosterone in healthy male volunteers. J Clin Endocrinol Metab 1999; 84: 3528–3533. Schiffrin EL. Effects of aldosterone on the vasculature. Hypertension 2006; 47: 312–318. Julius S, Jamerson K, Meija A, Krause L, Schork N, Jones K. The association of borderline hypertension with target organ changes and higher coronary risk: Tecumseh blood pressure study. JAMA 1990; 264: 354–358.