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<article article-type="editorial" dtd-version="1.0" xml:lang="en" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">CC</journal-id>
<journal-id journal-id-type="nlm-ta">Cardiol Croat</journal-id>
<journal-title-group>
<journal-title>Cardiologia Croatica</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Cardiol. Croat.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="ppub">1848-543X</issn>
<issn pub-type="epub">1848-5448</issn>
<publisher><publisher-name>Croatian Cardiac Society</publisher-name></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">CC_11(7)_215-217</article-id>
<article-id pub-id-type="doi">10.15836/ccar2016.215</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Editorial</subject></subj-group>
</article-categories>
<title-group>
<article-title>Prevention of Cardiovascular Diseases in 2015</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-2776-9675</contrib-id><name><surname>Kne&#x017E;evi&#x0107;</surname><given-names>Aleksandar</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib>
<aff id="aff1"><label>1</label>Working Group on Clinical Cardiovascular Pharmacology, Croatian Cardiac Society, <country>Croatia</country></aff>
<aff id="aff2"><label>2</label>Zadar General Hospital, Zadar, <country>Croatia</country></aff>
</contrib-group>
<author-notes>
<corresp id="cor1">Address for correspondence: Aleksandar Kne&#x017E;evi&#x0107;, Op&#x0107;a bolnica Zadar, Bo&#x017E;e Peri&#x010D;i&#x0107;a 5, HR-23000 Zadar, Croatia. / Phone: +385-23-505-505 / E-mail: <email xlink:href="aleksandar.knezevic@zd.t-com.hr">aleksandar.knezevic@zd.t-com.hr</email></corresp></author-notes>
<pub-date pub-type="ppub"><month>07</month><year>2016</year></pub-date>
<volume>11</volume>
<issue>7</issue>
<fpage>215</fpage>
<lpage>217</lpage>
<history>
<date date-type="received"><day>05</day><month>06</month><year>2016</year></date><date date-type="accepted"><day>21</day><month>06</month><year>2016</year></date>
</history>
<permissions>
<copyright-year>2016</copyright-year>
<copyright-holder>Croatian Cardiac Societly</copyright-holder>
</permissions>
</article-meta>
</front>
<body>
<p>Cardiovascular diseases (CVD) are still the leading cause of mortality in Croatia. According to the latest data for 2014, they were the cause of 47% of total deaths (coronary heart disease 21%, cerebrovascular disease 14%, and heart failure 3%). The mortality rate for these diseases is much higher in Croatian when compared with more developed European countries (from the EU15 group), but it is better than the average for other countries in the European region of the World Health Organization composed of the so-called transitional countries (340/100,000 inhabitants in Croatia; 160 for EU15 countries; 630 for transitional countries) (<xref ref-type="bibr" rid="r1"><italic>1</italic></xref>). Although there have been advancements in CVD treatment in comparison with earlier times, they are still the leading public health problem, and it is crucial to ensure the availability of all existing treatment approaches that we can provide, given our conditions.</p>
<p>Of course, CVD prevention is even more important than treatment because it allows us to achieve greater results with fewer resources. According to studies performed in various populations, as much as 44-76% of coronary heart disease mortality reduction is ascribed to prevention and changes in health-risk behavior, while 23-47% of mortality reduction is a result of treatment interventions. Prevention results in Croatia have so far been unsatisfactory (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>).</p>
<p>Significant advances in CVD prevention have been achieved over the last year. This is a result of:</p>
<list id="L1" list-type="bullet"><list-item><p>Reducing cardiovascular events in high-risk patients though diet and modification of unhealthy lifestyles.</p></list-item>
<list-item><p>Introducing new imaging methods that allow earlier detection of subclinical atherosclerosis, which leads to better CVD prevention.</p></list-item>
<list-item><p>New clinical evidence that plaque rupture at the culprit lesion happens in only 50-77% of patients with acute coronary syndrome.</p></list-item>
<list-item><p>Evidence from clinical trials on the effectiveness of treatment based on monoclonal antibodies targeting PCSK9, which leads to significant reduction in LDL cholesterol and consequently a reduction in CV events.</p></list-item>
<list-item><p>Significant reduction of cardiovascular and total mortality in patients with diabetes treated with empagliflozin (a SGLAT-2 inhibitor), demonstrated in the EMPA-REG OUTCOME clinical trial.</p></list-item>
<list-item><p>Improved management of arterial hypertension, especially resistant hypertension, through the application of spironolactone in the PATHWAY-2 and PATHWAY-3 clinical trials, and the application of the combination of amiloride and hydrochlorothiazide treatment in patients using diuretics to treat hypertension.</p></list-item>
<list-item><p>Reduced mortality in patients with arterial hypertension with target systolic blood pressure values of 120 mmHg in the SPRINT clinical trial.</p></list-item></list>
<p>All of the above has led to better control of: dyslipidemia, hyperglycemia, and hypertension, resulting in progressive reduction of atherosclerotic vascular disease and cardiovascular events in high-risk patients.</p>
<p>In a review article on the state of CVD prevention in 2015, Chapman et al. (<xref ref-type="bibr" rid="r3"><italic>3</italic></xref>) attributed the greatest significance for cardiovascular prevention to good regulation of LDL cholesterol, citing the registration of two drugs that act on the inhibition of PCSK9 in the plasma, and consequently on the reduction of LDL cholesterol values, as an important advancement in cardiovascular prevention (especially in patients with a family hypercholesterolemia). These two drugs (monoclonal antibodies) under the trade names Praluent<sup>&#x00AE;</sup> (alirocumab) and Repatha<sup>&#x00AE;</sup> (evolocumab) have been registered in the European Union in 2015 and thus automatically in Croatia as well. It is not yet know when they will be placed on the medication List of the Croatian Health Insurance Fund, given the current price of monthly treatment of approx. 5,000 HRK.</p>
<p>The importance assigned to hypolipidemic therapy in our country is demonstrated by the expenditure of medication for the regulation of dyslipidemia (mostly statins), which has grown sharply over the last decade (2004-2014) in DDD/100 inhabitants from 28.13 to 61.79, which is more than double. (<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>) However, since CVD are the leading cause of mortality and morbidity in Croatia, this increase in the use of hypolipidemic agents should definitely be larger, especially since elevated cholesterol values are also, along with smoking, the most important risk factor in our country. Thus, one trial on &quot;healthy&quot; participants found a prevalence of cholesterol levels above 5.5 mmol/L in 67% of the participants5 (<xref ref-type="bibr" rid="r5"><italic>5</italic></xref>)</p>
<p>In addition to dyslipidemia regulation, adequate regulation of blood pressure (BP) is still very significant and still not satisfactory in Croatia. A recent study found that only a quarter of patients have well-regulated BP values (<xref ref-type="bibr" rid="r6"><italic>6</italic></xref>). Chapman et al. (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>) cite two studies regarding arterial hypertension regulation: PATHWAY 2 and PATHWAY 3. (<xref ref-type="bibr" rid="r7"><italic>7</italic></xref>, <xref ref-type="bibr" rid="r8"><italic>8</italic></xref>) The PATHWAY 2 study examined the role of spironolactone in the treatment of resistant arterial hypertension (AH), where it showed good results. (<xref ref-type="bibr" rid="r7"><italic>7</italic></xref>) The results of the PATHWAY 3 study showed that the combination of amiloride and hydrochlorothiazide treatment was the preferred diuretic in the treatment of hypertensive patients due to its neutral metabolic effects. (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>) This drug, which had been available under the name Moduretic<sup>&#x00AE;</sup> in Croatia for many years, has unfortunately been withdrawn from the market last year, most likely due to commercial reasons. It remains to be seen how the guideline authors for AH treatment will receive the results of this study, but it will likely result in this drug once again becoming available in Croatia.</p>
<p>According to the latest European and American guidelines, AH management was less strict than before. However, this relaxation in the recommended target AP values has been brought into question by the recently published results of the SPRINT study in which patients that achieved AT values from 120/80 mmHg had 25% better cardiovascular outcomes (myocardial infarction, stroke, heart failure, acute coronary syndrome, cardiovascular death) than those with AP values at 140/90 mmHg. This was accompanied with an increase in the number of side-effects (hypotension, syncope, electrolyte imbalance, renal failure) in patients from the group with intensive pressure control (4.7 vs. 2.5%) (<xref ref-type="bibr" rid="r9"><italic>9</italic></xref>). The authors also cite this study as significant for cardiovascular prevention.</p>
<p>A significant achievement from the field of cardiovascular prevention in the last year was the EMP-REG OUTCOME clinical study which demonstrated a significant reduction of cardiovascular and total mortality in patients with type 2 diabetes and high cardiovascular risk that used empagliflozin, a selective SGLAT-2 inhibitor. Since all new antidiabetics must pass cardiovascular safety studies after the &quot;rosiglitazone affair&quot;, i.e. must be proven not to increase cardiovascular morbidity and mortality, the results of this study show that one of them in fact reduces them (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>).</p>
<p>In conclusion, the Chapman et al. article on the news in cardiovascular prevention in 2015 once again stressed good risk factor management (dyslipidemia, hyperglycemia, and arterial hypertension), which saw dramatic advancements in the past year, according to the authors. It is significant that most medications that have achieved this are available in Croatia, so there should be no obstacles to significantly improving the prevention of cardiovascular diseases.</p>
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<ref-list>
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