1094 American Journal of Hypertension 29(9) September 2016
ORIGINAL ARTICLE
Ambulatory blood pressure (BP) monitoring provides more
information than conventional BP measurements mainly
because it records nighttime BP values. In most healthy indi-
viduals, nighttime BP dips by 10%–20% compared to day-
time BP values.
1
People with a less than 10% BP decline are
referred as “nondippers” and individuals with normal diur-
nal BP variation are termed “dippers.” A nondipping profle
is associated with target organ damage including renal dis-
ease and cardiovascular (CV) complications.
2,3
Te mecha-
nisms responsible for individual diferences between dipping
patterns are still not completely understood. However, data
from previous studies suggest that a nondipping profle of
diurnal BP variability is associated with coronary heart dis-
ease (CHD).
4
One of the possible mechanisms accounting
for an impaired diurnal BP pattern is autonomic nervous
system imbalance.
5
Impaired autonomic nervous system
activity has been observed in patients with CHD.
6
In addi-
tion, some studies have revealed that patients with a blunted
nocturnal decline in BP display the highest risk because this
pattern exposes these individuals to a greater CV load each
day.
2,7
Given the importance of a nondipping profle of BP as
a risk factor for CV complications, the infuence of genetic
variation on the diurnal BP pattern may be pivotal in CV
risk assessment in patients with CHD. However, despite the
signifcance of BP fall, little is known about its heritability. In
previously performed studies, the heritability of nocturnal
BP fall was estimated as 38% for systolic dipping and 9% for
diastolic dipping.
8
Although some studies have confrmed
heredity of blunted nighttime BP dip in the general popula-
tion, no study has addressed heredity of nighttime BP dip
in patients with confrmed CHD. In the present study that
includes patients with CHD, we aim to determine which sin-
gle-nucleotide polymorphisms (SNPs) are related to blunted
nighttime BP fall.
METHODS
Subjects
Te present study recruited 1,345 CHD individuals con-
secutively admitted to Department of Cardiology, Medical
University of Gdansk (between August 2003 and August
The Relationship Between Gene Polymorphisms and
Dipping Profle in Patients With Coronary Heart Disease
Marcin Wirtwein,
1
Olle Melander,
2
Marketa Sjőgren,
2
Michal Hofmann,
3
Krzysztof Narkiewicz,
3
Marcin Gruchala,
4
and Wojciech Sobiczewski
4
BACKGROUND
The aim of this study is to report the relationship between certain
single-nucleotide polymorphisms (SNPs) and blunted nighttime blood
pressure (BP) fall in patients with coronary artery disease confrmed by
coronary angiography.
METHODS
According to the percentage decrease in mean systolic BP (SBP)
and diastolic BP (DBP) during the nighttime period, subjects were
classified as dippers or nondippers (nighttime relative SBP or DBP
decline ≥10% and <10%, respectively). Genetic risk score (GRS18)
was constructed to evaluate additive effect of 18 SNPs for nondip-
ping status.
RESULTS
In the present study, 1,345 subjects with coronary heart disease (CHD)
were included. During follow-up period (median 8.3 years, interquartile
range 5.3–9.0 years), there were 245 all-cause deaths (18.2%) includ-
ing 114 cardiovascular deaths (8.5%). There were signifcant diferences
in the number of revascularizations between nondippers SBP and DBP
and dippers SBP and DBP (48.0% vs. 36.4%, P < 0.01). SNPs of the genes,
MIA3, MRAS, PCSK9, SMG6, and ZC3HC1, were related to a higher risk of
nondipping SBP and DBP status.
CONCLUSIONS
In the present study, polymorphisms of genes related to CHD (MIA3,
MRAS, PCSK9, SMG6, and ZC3HC1) were associated with nondipping SBP
and DBP profle, and GRS18 was associated with nondipping status. In
addition, this profle was related to a higher risk of revascularization.
Keywords: blood pressure; coronary artery disease; dipping; DNA poly-
morphisms; hypertension.
doi:10.1093/ajh/hpw040
Correspondence: Marcin Wirtwein (marwirt@interia.pl).
Initially submitted November 24, 2015; date of frst revision December
12, 2015; accepted for publication February 29, 2016; online publication
May 17, 2016.
© American Journal of Hypertension, Ltd 2016. All rights reserved.
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1
Department of Pharmacology, Medical University of Gdansk, Gdansk,
Poland;
2
Department of Clinical Sciences, Lund University, Malmö,
Sweden;
3
Department of Hypertension and Diabetology, Medical
University of Gdansk, Gdansk, Poland;
4
Department of Cardiology,
Medical University of Gdansk, Gdansk, Poland.
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