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Received: 12 January 2018 Revised: 23 February 2018 Accepted: 11 March 2018 DOI: 10.1111/jch.13283
ORIG INAL PAPER
Effects of different statin types and dosages on systolic/ diastolic blood pressure: Retrospective analysis of 24-hour ambulatory blood pressure database Vivianne Presta MD1
| Ilaria Figliuzzi MD1
| Barbara Citoni MD1 |
Francesca Miceli MD1 | Allegra Battistoni MD1 | Maria Beatrice Musumeci MD1 2
1
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1
Roberta Coluccia MD | Luciano De Biase MD | Andrea Ferrucci MD | Massimo Volpe MD1,2
| Giuliano Tocci MD, PhD1,2
1 Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant’Andrea Hospital, University of Rome Sapienza, Rome, Italy 2
IRCCS Neuromed, Pozzilli, Italy
Correspondence Giuliano Tocci, MD, PhD, Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy. Email:
[email protected]
We previously demonstrated lower diastolic blood pressure (BP) levels under statin therapy in adult individuals who consecutively underwent 24-hour ambulatory BP monitoring and compared their levels to untreated outpatients. Here we evaluated systolic/diastolic BP levels according to different statin types and dosages. 987 patients (47.5% female, age 66.0 ± 10.1 years, BMI 27.7 ± 4.6 kg/m2, clinic BP 146.9 ± 19.4/86.1 ± 12.1 mm Hg, 24-hour BP 129.2 ± 14.4/74.9 ± 9.2 mm Hg) were stratified into 4 groups: 291 (29.5%) on simvastatin 10-80 mg/d, 341 (34.5%) on atorvastatin 10-80 mg/d, 187 (18.9%) on rosuvastatin 5-40 mg/d, and 168 (17.0%) on other statins. There were no significant BP differences among patients treated by various statin types and dosages, except in lower clinic (P = .007) and daytime (P = .013) diastolic BP in patients treated with simvastatin and atorvastatin compared to other statins. Favorable effects of statins on systolic/diastolic BP levels seem to be independent of types or dosages, thus suggesting a potential class effect of these drugs.
1 | I NTRO D U C TI O N
in out of office-treated hypertensive patients, suggesting that other factors might be implied.
Essential hypertension is related to an increased risk of major car-
Hypercholesterolemia is frequently observed in hypertensive
diovascular events such as myocardial infarction, stroke, conges-
populations,7-9 further contributing to the enhancement of individ-
tive heart failure, and end-stage renal disease, making it the most
ual global cardiovascular risk profiles and enhancing individual sus-
1
common cardiovascular risk factor in the global adult population.
ceptibility to major cardiovascular complications, especially coronary
Risk related to hypertension can be reduced by achieving the rec-
artery disease.10 An integrated pharmacological approach based on
2
ommended clinic blood pressure (BP) targets and evidence show
the concomitant use of BP and total cholesterol-lowering drugs has
that to reduce the burden of hypertension-related cardiovascular
been shown to reduce the risk of major cardiovascular complications
morbidity and mortality, effective and sustained (24-hour period)
in large randomized controlled clinical trials performed in high-risk
BP control should be pursued in a clinical practice setting.3,4 For this
individuals11-16 and diabetic patients.17-20 However, these trials were
reason, closer scrutiny has been progressively devoted to out-of-
based on the assessment of clinic BP levels; thus, the effects of com-
office BP measurements and antihypertensive strategies aimed at
bined pharmacological interventions on 24-hour BP levels (mostly
maintaining BP reductions and control over an entire 24-hour pe-
during nighttime) and their potential implications on the risk of car-
riod.5,6 This is because cardiovascular risk often remains elevated
diovascular diseases remain to be clarified.
J Clin Hypertens. 2018;20:967–975.
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In this latter regard, we have recently demonstrated that use of
rosuvastatin 5 mg, (2) medium dose: simvastatin 20 mg, atorvastatin
statin therapy is associated with significantly lower diastolic BP lev-
20 mg, rosuvastatin 10 mg, (3) full dose: simvastatin 40-8 0 mg, ator-
els during 24-hour ambulatory BP monitoring, independent of the
vastatin 40-8 0 mg, rosuvastatin 20-4 0 mg. 24
presence or absence of antihypertensive therapy or any number of
The study conformed to the Declaration of Helsinki and its sub-
antihypertensive drug classes. 21 Of note, the favorable effects of
sequent modifications. The confidentiality of the data of each patient
statin therapy on diastolic BP was consistently observed during both
included in the present study was carefully and strictly protected.
clinic and ambulatory BP measurements, particularly so during the
Informed consent was obtained from all individuals included in the
nighttime period, when no significant differences were observed
present study, which was approved by the local ethics committee.
with regard to the clinic and 24-hour ambulatory systolic BP levels. 21 The latter may have potential clinical implications, due to the well- known correlation between nighttime BP levels and increased risk of cardiovascular and cerebrovascular events. 22,23
2.2 | Home, clinic, and 24-hour ambulatory blood pressure measurements
In this predefined analysis, we focused our attention on the sub-
As applied in the previous analysis, 21 all BP measurements were per-
groups of patients under statin therapy with the aim of identifying
formed according to recommendations by European guidelines. 25
potential differences among drugs and molecules with regard to
In particular, clinic BP measurements were performed in the hy-
systolic/diastolic BP levels by analyzing data derived from the same
pertension clinic during the morning section (8:00 am to 10:00 am).
database of adult patients undergoing 24-hour ambulatory BP mon-
Sequential BP measurements were performed after 10 minutes of
itoring at our hypertension unit.
rest on the same arm with the participant in the sitting position in a quiet room using an automated oscillometric device (Omron 705 IT).
2 | M E TH O DS 2.1 | Study population
The average of 3 consecutive BP measurements and heart rate was considered as clinic systolic/diastolic BP levels. 25 ABPM was performed using an oscillometric device (Spacelabs 90207) in the hypertension unit after completion of the clinic BP
As applied in the previous analysis, 21 we extracted data from the
measurements and started at approximately 10:00 am. Automatic BP
same medical database, which included clinical records derived from
readings were obtained every 15 minutes during the daytime period
adult individuals who were consecutively evaluated for full BP as-
(6:00 am to 22:00 pm) and every 30 minutes during the nighttime pe-
sessment (home, clinic, and 24- hour ambulatory BP monitoring)
riod (from 22:00 pm to 6:00 am) over the 24 hours. 25 Each patient
at the outpatient service of our hypertension unit at Sant’Andrea
was instructed not to alter her/his usual schedule during the mon-
Hospital between January 2007 and December 2016. 24-hour am-
itoring period, to avoid unusual physical activities, and to maintain
bulatory BP monitoring is a common practice at our unit and applied
stillness of the arm during the BP measurements. Average values
for both diagnostic and therapeutic purposes to either hypertensive
for the 24-hour, daytime and nighttime systolic and diastolic BP
outpatients or high-risk individuals. To be included in the study pro-
levels, and heart rate were reported. Also, BP load, defined as the
tocol, participants had to present the following inclusion criteria: (1)
number of BP measurements above the normal BP thresholds, was
individuals aged more than 30 years and (2) signature of informed
reported for each time period (24-hour, daytime, and nighttime) in
consent for study participation. In addition, the following exclusion
each participant. 25
criteria were considered: (1) recent (< 6 months) history of acute cardiovascular disease, including at least one of the following: coronary artery disease, stroke, congestive heart failure, severe valve disease, or peripheral artery disease; (2) any neurological or psychiatric dis-
2.3 | Definition of cardiovascular risk factors and comorbidities
ease which may at least, in part, affect the BP assessment or the
Diagnosis of hypertension was made in the presence of clinic sys-
signature of the informed consent.
tolic/diastolic BP levels ≥ 140/90 mm Hg or in the presence of stable
Once included in the analysis, patients were initially stratified
(>6 months) antihypertensive drug treatment in subsequent visits. 25
into 2 groups, depending on the presence or the absence of statin
Diagnosis of hypercholesterolemia was made in the presence of total
therapy. 21 In this regard, time for drug assumption was indicated in
cholesterol levels ≥ 190 mg/dL or LDL cholesterol levels ≥ 130 mg/
patients’ diary and then reported in the database for the analysis.
dL, while hypertriglyceridemia for triglyceride levels ≥ 150 mg/dL or
Thus, in our population sample, all statins have been assumed be-
stable lipid-lowering drug treatment in both conditions. 26 Diabetes
tween 20.00 and 22.00.
was defined in the presence of plasma glucose levels ≥ 126 mg/dL or
In the present analysis, only patients on statin therapy were
in the presence of glucose-lowering therapy. 27
considered and stratified into different groups, depending on type
Coronary artery disease (CAD), including non-fatal myocardial
(simvastatin 10-8 0 mg daily, atorvastatin 10-8 0 mg daily, rosuvas-
infarction (MI), was defined as the presence of the 2 of the follow-
tatin 5-4 0 mg daily, others) and dosages (low, medium, full dose)
ing 3 items: (1) symptoms (eg, chest pain) lasting longer than 15 min,
of statins. In particular, daily dosages of statins were considered
(2) transient increase in serum concentrations of enzymes indicating
as follows: (1) low dose: simvastatin 10 mg, atorvastatin 10 mg,
cardiac damage (more than twice the upper limit of normal), and (3)
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PRESTA et al.
electrocardiographic changes typical of myocardial ischemia (new
2 groups). Differences for systolic/diastolic BP levels among various
persistent ST-segment elevation or pathological Q waves in 2 con-
statin groups were also adjusted for potential confounding factors,
tiguous leads). 28,29 The diagnosis of CAD may also include other cor-
including age, gender, BMI, diabetes, and presence of antihyperten-
onary events, including acute coronary syndrome, recurrent angina,
sive therapy, by adopting univariate general linear model with least
and coronary revascularization.30
square deviation for multiple comparisons. Categorical variables
Non-fatal stroke was defined as a neurological deficit with sud-
were compared among groups by the chi-squared test. All tests were
den onset and persistence of symptoms for more than 24 hours or
two-sided, and a P value of less than .05 was considered statistically
leading to death with no apparent causes other than vascular ones.31
significant. All calculations were generated using SPSS, version 20.0.
Transient ischemic attack (TIA) was defined as a neurological event with the signs and symptoms of stroke that go away within a short period (typically lasting 2-30 minutes).32
3 | R E S U LT S 3.1 | Study population
2.4 | Statistical analysis
Flowchart for selecting the study population is illustrated in Figure
All data were entered into Microsoft Access for Windows (Microsoft
S1. From an overall population sample of 7216 adult outpatients who
Office). Given the retrospective, descriptive nature of the study, no
underwent full BP assessment at our hypertension unit, 415 (5.7%)
calculation sample analysis was made, and all patients included in the
individuals aged less than 30 years were excluded, and 301 (4.2%)
medical database were initially considered. Baseline characteristics
items were omitted due to partial or missing BP data, thus leading to
of patients are presented as number and percentage for dichotomous
a remaining sample of 6500 adult outpatients aged 30 years or more,
variables and mean ± standard deviation of the mean for continuous
which represents the 90.1% of the initial population. This popula-
variables. Normal distribution of data was assessed using histograms
tion was initially stratified into 2 groups, depending on the presence
and Kolmogorov-Smirnov test. Differences between continuous
(n = 987; 15.2%) or absence (n = 5,513; 84.8%) of statin therapy. In
variables were assessed using either Student’s t-test (comparison
the present analysis, we considered only patients under statin ther-
between 2 samples) or ANOVA test (comparisons among more than
apy, who were further stratified into 4 groups, depending on drug
TA B L E 1 General characteristics of the patients treated with different statin types
Parameters
Simvastatin
Atorvastatin
Rosuvastatin
Other statins
P value
Individuals (%)
291 (29.5)
341 (34.5)
187 (18.9)
168 (17.0)
-
Female (%)
133 (45.7)
144 (42.2)
99 (58.9)
.004
Age (y)
67.2 ± 9.0*
67.1 ± 10.3*
65.1 ± 9.9
93 (49.7)
62.7 ± 11.1
