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Tahkola et al. BMC Family Practice
(2020) 21:62
https://doi.org/10.1186/s12875-020-01138-5
RESEARCH ARTICLE
Open Access
Lifetime risk assessment in cholesterol
management among hypertensive patients:
observational cross-sectional study based
on electronic health record data
Aapo Tahkola1,2*, Päivi Korhonen3, Hannu Kautiainen4, Teemu Niiranen5,6 and Pekka Mäntyselkä1,7
Abstract
Background: In hypertensive patients, reducing plasma low-density lipoprotein cholesterol level (LDL-C) is one of
the main interventions for preventing chronic cardiovascular diseases (CVD). However, LDL-C control remains
generally insufficient, also in patients with hypertension. We analyzed Electronic Health Record (EHR) data of 7117
hypertensive patients to find the most potential age and sex subgroups in greatest need for improvement in real
life dyslipidemia treatment. Taking into account the current discussion on lifetime CVD risk, we focused on the age
dependence in LDL-C control.
Methods: In this observational cross-sectional study, based on routine electronic health record (EHR) data, we
investigated LDL-C control of hypertensive, non-diabetic patients without renal dysfunction or CVD, aged 30 years
or more in Finnish primary care setting.
Results: More than half (54\% of women and 53\% of men) of untreated patients did not meet the LDL-C target of < 3
mmol/l and one third (35\% of women and 33\% of men) of patients did not reach the target even with the lipidlowering medication (LLM). Furthermore, higher age was strongly associated with better LDL-C control (p < 0.001) and
lower LDL-C level (p < 0.001) in individuals with and without LLM. Higher age was also strongly associated with LLM
prescription (p < 0.001). In total, about half of the patients were on LLM (53\% of women and 51\% of men).
Conclusions: Our findings indicate that dyslipidemia treatment among Finnish primary care hypertensive patients is
generally insufficient, particularly in younger age groups who might benefit the most from CVD risk reduction over
time. Clinicians should probably rely more on the lifetime risk of CVD, especially when treating working age
hypertensive patients.
Keywords: Dyslipidemia, Hypertension, Lifetime risk, Lipid-lowering medication, LDL-C, Target
* Correspondence: aapo.tahkola@jkl.fi
1
University of Eastern Finland, Institute of Public Health and Clinical Nutrition,
Kuopio, Finland
2
Health Centre of Jyväskylä Cooperation Area, Jyväskylä, Finland
Full list of author information is available at the end of the article
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if
changes were made. The images or other third party material in this article are included in the articles Creative Commons
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licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the
data made available in this article, unless otherwise stated in a credit line to the data.
Tahkola et al. BMC Family Practice
(2020) 21:62
Background
Dyslipidemia increases the risk for cardiovascular diseases
(CVD) considerably, especially when combined with other
risk factors, such as hypertension [1, 2]. The relationship
between dyslipidemia and CVD is particularly strong with
plasma low-density lipoprotein cholesterol level (LDL-C)
as every 1 mmol/L increase in LDL-C is associated with
28\% risk increase in coronary heart disease mortality [3].
Reducing LDL-C is therefore one of the central focuses in
preventing CVD, also in hypertensive patients.
Treatment decisions should always be based on the
total risk for CVD. The majority of hypertensive patients
without CVD, diabetes or moderate to severe chronic
kidney disease (CKD; stages 3–5) have low to moderate
risk for CVD [3]. According to the 2016 European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Guidelines for the Management of
Dyslipidaemias, the target for individuals at low or moderate total CVD risk for treatment is LDL-C < 3 mmol/l
[3]. Lifestyle changes are essential as a first approach but
with hypertensive patients, who have moderate-high CV
risk, lipid-lowering therapy is justified [4–9].
Recent studies demonstrate that LDL-C control remains
quite insufficient in Finland and other European countries,
even among high CVD risk populations [10, 11].. LDL-C
control seems to be especially poor in younger age groups
in many countries and patient groups [11–14]. This is an
important signal, given the accumulating evidence on the
benefits of adequate LDL-C –control over time and growing interest on life-long prevention of CVD [15–19].
The aim of this study was to analyze routine EHR data
of hypertensive patients in order to find the most potential age and sex subgroups in greatest need for improvement in dyslipidemia treatment. We were particularly
interested on potential age dependence in LDL-C control based on the viewpoint of lifetime CVD risk.
Page 2 of 7
laboratory and medication data between between January
2011 and December 2015.
Patients
We included all hypertensive patients aged 30 years or
more. The identification of patients was based on the personal identity code. Every citizen of Finland has a personal
identity code that remains unchanged throughout person’s
lifetime. We included patients with presence of ≥1 claims
with International Classification of Diseases, Tenth Revision (ICD-10) code for essential hypertension (I10.xx)
[21]. We included diagnostic codes starting from the year
2011. Since the diagnostic criteria for hypertension has
changed from time to time and the diagnoses of hypertension for individual study patients has been made over a
relatively long time period, it is not possible to define specific diagnostic values for hypertension in our study patients. Exclusion criteria were: (1) diabetes (E10.xxE14.xx), (2) cardiovascular disease (ischemic heart disease
I20.xx – I25.xx, stroke I60.xx – I63.xx, peripheral artery
disease I70.xx – I79.xx), (3) severe renal dysfunction and
(4) age under 30 years. The presence of severe renal dysfunction was based on an estimated glomerulus filtration
rate (eGFR < 30 ml/min/1.73 m2) [22]. Patients with diabetes were excluded because our data did not allow us to
identify patients with microvascular diabetic complications and, therefore, setting the right target level for diabetics was not possible. Patients < 30 years of age were
excluded because the small amount of patients (n = 71)
made it impossible to carry out a feasible analysis. The
screening process is presented in Fig. 1. LDL-C target was
considered to be < 3 mmol/l, according to European and
Finnish treatment guidelines [3, 23].
Statistical analyses
Setting
The characteristics are presented as means with standard deviation (SD) for continuous variables and as frequencies with percentages for categorical variables,
according to gender. Statistical comparisons between
groups were done using chi-square test, t-test and generalized linear models (analysis of variance and logistic
models). Tests for interactions between LLM-group or
gender and age group were conducted by adding a
multiplicative term between group or gender and the
age group. The normality of the variables was tested by
using the Shapiro-Wilk W test. Adjustment for multiple
comparisons was considered unnecessary. The Stata
14.1, StataCorp LP (College Station, TX, USA) statistical
package was used for the analysis.
The study was conducted in Finnish public primary care
setting in Jyväskylä area. The comprehensive electronic
health record data of total population of 155,411 was
screened on 24th of May, 2016. The data included
Results
A total of 7117 hypertensive patients were identified
from the EHR data. Table 1 displays the patients’ co-
Methods
In this observational cross-sectional study using routinely collected health care data together with laboratory
data, we investigated the level of plasma LDL-C among
Finnish hypertensive patients. The most recent LDL-C
measurement available for each individual patient was
used in the analysis. Permission for this study was obtained from the research committee of Health Centre of
Jyväskylä Cooperation Area and it complies with the
Declaration of Helsinki. Ethics approval was deemed unnecessary according to Finnish legislation [20].
Tahkola et al. BMC Family Practice
(2020) 21:62
Page 3 of 7
Fig. 1 The screening process of the study. eGFR: Estimated glomerulus filtration rate; LDL-C: Low-density lipoprotein
morbidities, medication usage and LDL-C levels according to gender.
In total, 65\% of hypertensive women and 67\% of hypertensive men treated with LLM reached the LDL-C target < 3
mmol/l. Without LLM, the proportion of patients reaching
the target was even lower (46\% of women and 47\% of men).
Of all patients, 56\% of hypertensive patients reached the LDLC target. The proportions of individuals reaching treatment
target with and without medication is presented in Table 2.
The proportion of women and men reaching the LDLcholesterol target level rose statistically linearly with increasing age (p-value for linearity < 0.001). The proportion
of patients receiving LDL-C target was higher with the patients with LLM, with the exception of two subgroups:
women and men aged 30–49 years, and among men at
least 80 years of age (Fig. 2).
Accordingly, the mean plasma LDL-cholesterol level
decreased linearly with increasing age whether LLM was
prescribed or not (p-value for linearity < 0.001) (Fig. 3).
In the age group of 30–49 years, LLM was prescribed to
10.3\% of the women and 24.5\% of the men. The percentage of patients with LLM rose linearly across older age
groups being 63.1\% in women and 59.4\% in men aged
70–79 years (p-value for linearity < 0.001) (Fig. 4).
Table 1 Characteristics of study patients
Women N = 4344
Men N = 2773
P-value
70 (12)
66 (12)
< 0.001
2310 (53)
1400 (50)
0.027
Other cardiac therapy e.g. antiarrhythmics, nitrates (C01)
936 (22)
429 (15)
< 0.001
ACE-inhibitors, Angiotensin II antagonists (C09)
3531 (81)
2330 (84)
0.003
Diuretics (C03)
1370 (32)
538 (19)
< 0.001
Beta blockers (C07)
2477 (57)
1312 (47)
< 0.001
Demographics
Mean age (years), mean (SD)
Medication (ATC), n (\%)
Lipid-lowering medication (C10)
Calcium Channel Blockers (C08)
2150 (49)
1379 (50)
0.85
Other antihypertensives (C02)
114 (3)
73 (3)
0.97
Heart failure (I50)
95 (2)
31 (1)
< 0.001
Atrial fibrillation and flutter (I48)
295 (7)
207 (7)
0.28
All
2.88 (0.88)
2.85 (0.88)
< 0.001a
With LLM
2.75 (0.97)
2.68 (0.98)
< 0.001a
Without LLM
3.03 (0.73)
3.01 (0.73)
0.25a
Co-morbidity (ICD-10), n (\%)
Plasma LDL-C level, mean (SD)
Abbreviations. LLM lipid lowering medication, LDL-C low-density lipoprotein
a
Adjusted for age
Tahkola et al. BMC Family Practice
(2020) 21:62
Page 4 of 7
Table 2 Proportion of individuals reaching LDL-C target
Age 30–49
Age 50–59
Age 60–69
Age 70–79
Age 80 -
Total
119 (50.4)
132 (37.5)
250 (41.5)
235 (47.2)
192 (55.7)
928 (45.6)
15 (55.6)
75 (48.1)
436 (62.1)
595 (70.0)
383 (66.6)
1504 (65.1)
80 (41.2)
100 (36.8)
207 (46.1)
175 (54.4)
90 (66.2)
652 (47.5)
27 (42.9)
90 (54.9)
362 (68.2)
337 (71.6)
121 (70.8)
937 (66.9)
27 (10.3)
156 (30.7)
702 (53.8)
850 (63.0)
575 (62.5)
2310 (53.2)
63 (24.5)
164 (37.6)
531 (54.2)
471 (59.4)
171 (55.7)
1400 (50.5)
LDL-C TARGET REACHED
Women without LLM
Yes, n (\%)
Women with LLM
Yes, n (\%)
Men without LLM
Yes, n (\%)
Men with LLM
Yes, n (\%)
LIPID-LOWERING MEDICATION
Women
Yes, n (\%)
Men
Yes, n (\%)
Abbreviations. LDL-C low-density lipoprotein, LLM lipid-lowering medication
Discussion
Our study indicates that LDL-C control among Finnish
hypertensive patients is insufficient, especially among younger patients. Without LLM, more than half of patients did
not reach LDL-C target and even with medication, one
third of patients did not meet the target. Furthermore, the
proportion of individuals reaching LDL-C target seems to
be lowest among working age patients who might benefit
the most from CVD risk reduction over time [17, 18].
It is clear that younger patients have significantly lower
total CVD risk than older patients when assessed using
conventional short-term (generally 10-year) risk estimates.
Due to current emphasis on short-term risk estimates, clinicians often choose not to initiate effective dyslipidemia
treatment when short-term risk is low due to young age.
It is remarkable, however, that all our study patients had
at least one major CVD risk factor (treatment for hypertension), indicating that proper treatment of another
major risk factor (hypercholesterolemia) would decrease
the lifetime risk of CVD considerably [18].
Furthermore, it is challenging to rationalize why patients who are on LLM treatment are not treated to a
Fig. 2 Association between age and proportion reaching LDL-C target. LDL-C: Low-density lipoprotein; LLM: Lipid-lowering medication
Tahkola et al. BMC Family Practice
(2020) 21:62
Page 5 of 7
Fig. 3 Association between age and plasma LDL-C levels. LDL-C: Low-density lipoprotein; LLM: Lipid-lowering medication
relatively easy-to-reach LDL-C target of < 3 mmol/l, regardless of age. With these individuals, the question is not
“Should we treat cholesterol with drugs or not?” but rather:
“Should we use the chosen medication properly or not?”.
Poor medication adherence often forms a barrier for successful therapy, together with clinical inertia [3, 24, 25]. We
argue, however, that lack of sufficient, individual physician
feed-back and robust leadership engagement to overcome
clinical inertia are also major, but modifiable reasons for
this failure. Computerized decision support systems could
offer one way to drive change for the better, but feedback
alone is not sufficient for system-wide change [26, 27].
Strengths and limitations
Fig. 4 Association between age and lipid-lowering medication use.
LDL-C: Low-density lipoprotein; LLM: Lipid-lowering medication
This study has several strengths. To our knowledge, this is
the first article to focus on age dependence in LDL-C control among hypertensive patients. Furthermore, Finland has
robust public health care and majority of hypertensive patients are treated in public primary health care [28]. To
conduct the study, we were able to rely on comprehensive
public health care health records of a total population of
over 155,000 individuals living in Central Finland (http://
pxnet2.stat.fi/PXWeb/pxweb/en/StatFin/StatFin__vrm__
vaerak/010_vaerak_tau_123.px/?rxid=ada87756-a322-4f53b48e-78fdc85edfa2). Hence, the EHR database used in our
study includes the majority of all hypertensive patients
treated in this area.
Our study has also some limitations that are worth
discussion. This was an observational cross-sectional
study using routinely collected health care data together
with laboratory data. These data sources have naturally
several limitations. First, they do not provide sufficient
information to assess total individual CVD risk.
Tahkola et al. BMC Family Practice
(2020) 21:62
Therefore, we focused only in hypertensive population
without CVD, diabetes or severe renal dysfunction. It is
therefore reasonable to assume that LDL-C treatment
targets of the general population are used in these patients [3, 9, 23]. Second, these data sources lack trustworthy information on smoking and current blood
pressure status. This would be a major problem in prognostic study setting, but is not essential when studying the
treatment status of an independent risk factor, such as
LDL-C. Smoking and the blood pressure level of hypertensive patients do not change the LDL-C target levels, either.
Third, the coverage and accuracy of diagnostic codes is
never perfect, and may have resulted in misclassification
of some patients, especially diabetics. However, the EHR
data used in the study has also been a basis of a rigorous
quality measurement system for several years and the
accuracy of diagnostic codes has therefore enhanced
remarkably. When analysing the data, we were also able to
perform multiple chart reviews and found no signs of
major misclassification. It is also possible that better target
achievement in older age groups is partly due to more frequent use of health services due to increased multimorbidity, but we were not able to detect and compare our
findings with the use of health services. Furthermore, it is
probable, that some working age patients visit both primary and occupational health care and their LDL-C level
may thus be treated to target in occupational health care
after being first measured in primary health care. Finally,
the status of LLM treatment in this study was based on
up-to-date information of LLM prescription but our data
does not provide reliable information on the adherence to
medication or non-medical treatment of dyslipidemia.
Comparison with existing literature
Some previous studies have observed a similar age
dependent trend in the proportion of individuals reaching
LDL-C target [11–14]. It might seem reasonable to assume
that physiological changes of aging could explain the better
LDL-C control among older patients. However, it has been
shown that both plasma LDL-C and total cholesterol levels
increase progressively after age of 20 years [29, 30]. One explanation seems to be better LLM adherence among older
patients [31]. However, the pattern of age-dependent increase in LDL-C is different between men and women and
may thus, at least partly, explain the somewhat weaker association of age and LDL-C -levels among women [32].
Earlier, the gender differences in the proportion of
men and women reaching LDL-C target have already
raised a need to pay special attention to treatment of
dyslipidemia in women [14]. Our results suggest that it
is now time to pay more attention to younger dyslipidemia patients, as well. This is further emphasized by
earlier research findings indicating that younger age is
also associated with lower awareness and treatment rates
Page 6 of 7
of elevated blood pressure in Finland [33]. Lifetime risk
estimates of CVD are developing rapidly and open access lifetime risk calculators are already available [17,
34]. At least one on-going randomised, controlled clinical study is currently investigating 10-year benefits of
statin treatment in 35–59 year-old patients with LDLC > 1.8 mmol/L and at least one risk factor other than
dyslipidemia [16].
Conclusions
Our findings suggest that working age patients might be
the most potential subgroup to enhance LDL-C control
and CVD risk reduction among Finnish hypertensive primary health are patients. Focusing more on the lifetime
risk of CVD might help primary care physicians to make
better informed decisions on dyslipidemia treating among
younger hypertensive patients. This should, however, be
further examined in different patient populations.
Abbreviations
CVD: Cardiovascular diseases; CKD: Chronic kidney disease; EAS: European
Atherosclerosis Society; eGFR: Estimated glomerulus filtration rate (CKD-EPI
equation); EHR: Electronic health record; ESC: European Society of Cardiology;
LDL-C: Low-density lipoprotein; LLM: Lipid-lowering medication
Acknowledgements
We thank Jyväskylä Cooperation Are ...
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