[Update on Current Care Guideline. Diabetes]. / Diabetes.

About 500,000 people suffer from diabetes in Finland, a number which is predicted to increase within the next decades. At the moment, diabetes can neither be prevented nor cured. Diabetes is associated with microvascular (kidney, eye and peripheral nerves) and macrovascular complications (coronary heart disease, stroke). These complications affect the quality of life of patients and account for a substantial proportion of healthcare costs in Finland. The.current guidelines offer recommendations for the diagnosis, screening, prevention and treatment of diabetes and its complications.

[Life after cardiac infarction]. / Elämä(ä) sydäninfarktin jälkeen.

Many of those having had cardiac infarction suffer only a minor myocardial injury and are discharged after balloon angioplasty with open coronary arteries and well-pumping cardiac muscle. Returning to normal life may, however, be tough. On the other hand, after a few days of hospital care the discharged person does not always even note having fallen ill. At and between both extremes the affected person needs guidance, support, encouraging and appropriate medication. Living habits have an essential effect on both short-term and long-term prognosis, and sensible living also results in a better well-being.

Heart rate variability associates with asymptomatic coronary atherosclerosis.

PURPOSE: Heart rate variability (HRV) becomes impaired in symptomatic coronary artery disease (CAD), particularly, after myocardial infarction. The mechanism how CAD results in impairment of cardiac autonomic regulation is not known. Whether it results rather from coronary atherosclerosis itself than myocardial ischemia and myocardial injury has remained elusive. METHODS: Quantitative coronary angiography was performed in 30 subjects without history of myocardial ischemia, but with high familial risk for CAD. HRV was measured from 24-h ambulatory ECG recordings in time and frequency domain and also non-linear HRV variables SD1 and SD2 in Poincare plot were calculated. Myocardial ischemia was excluded by Tc-99m sestamibi scintigraphy at rest and during exercise. RESULTS: Coronary angiography revealed mean diameter stenosis of 32 ± 19 % in left anterior descending coronary artery, 26 ± 16 % in left circumflex coronary artery and 25 ± 20 % in right coronary artery. An inverse correlation was found between pNN50 and global severity of coronary artery diameter stenosis (r = -0.415, p < 0.05). Correspondingly, power of HF spectral component correlated negatively with global extent of coronary atherosclerosis (r = -0.366, p < 0.05). In Poincare plot, SD1/SD2 ratio correlated with global extent (r = -0.394, p < 0.05) and global burden (r = -0.388, p < 0.05) of coronary arteries. CONCLUSIONS: The severity and extent of coronary atherosclerosis were related to a shift of cardiac autonomic regulation towards sympathetic predominance in asymptomatic subjects without evidence of myocardial ischemia.

[Prevention of arterial diseases in the 2010s: the European treatment guideline]. / Valtimosairauksien ehkäisy 2010-luvulla: eurooppalainen hoitosuositus.

Reduction of risk factors at the population level forms the basis of the European recommendation of 2012 for the prevention of arterial diseases. Actions at the individual level arise from risk assessment. The risk of arterial disease is graded into four categories, the uppermost ones comprising patients who have already developed the disease, diabetics, those suffering from renal insufficiency and those carrying a serious gene defect. In Finland the risk among healthy people is assessed by using the FINRISKI tool. Non-smoking, healthy diet and regular exercise are suitable for all. Statins are an effective and safe means of prevention for those at high risk regardless of lipid values.

[Statin therapy--for whom?]. / Kenelle aloitan statiinilääkityksen?

For patients with cardiovascular disease, statins belong to routine medical treatment irrespective of blood lipid levels. In primary prevention also, statins have been found to prevent cardiovascular diseases, associated deaths and decrease overall mortality. In previously healthy persons the use of statins should be based on the assessment of total risk--mere cholesterol level does not usually constitute an indication for treatment. The use of statins may lead to adverse effects, the major one being myopathy, for which an elevated risk is associated with increasing statin dosages.

Predicting the culprit artery in acute ST-elevation myocardial infarction and introducing a new algorithm to predict infarct-related artery in inferior ST-elevation myocardial infarction: correlation with coronary anatomy in the HAAMU Trial.

AIMS: The objective of this study is to predict the culprit artery from the electrocardiogram (ECG) by predefined criteria and to compare a new algorithm with a previous one for predicting the culprit artery in inferior ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: In "all-comers" (n = 187) with acute STEMI, with ECG and angiography from the acute phase, the positive and negative predictive values for the prediction of the left anterior descending coronary artery, left circumflex coronary artery, or right coronary artery as the infarct-related artery were 96% and 96%, 65% and 95%, 92% and 97%, respectively. In inferior STEMI (n = 98), positive and negative predictive values to predict the right coronary artery or the left circumflex coronary artery as the culprit artery were 92% and 75% and 75% and 94%, respectively. CONCLUSIONS: In "all-comers" with STEMI, the culprit artery could be predicted by ECG criteria with high predictive values. In inferior STEMI, a new algorithm for culprit artery prediction was successfully tested.

Apolipoprotein E polymorphism is associated with both carotid and coronary atherosclerosis in patients with coronary artery disease.

BACKGROUND AND AIMS: Apolipoprotein E (apoE) polymorphism plays a significant role in the development of atherosclerosis and cardiovascular disease. Therefore, the aim of the present study was to examine the association between apoE polymorphism and carotid intima-media thickness (IMT), and severity and extent of coronary artery disease (CAD). METHODS AND RESULTS: B-mode ultrasound and quantitative coronary angiography (QCA) were used to assess carotid, and coronary artery atherosclerosis in 91 patients with clinically suspected CAD referred for cardiac catheterization. Two apoE phenotype groups were defined: apoE3 (E3/E3) and apoE4 (including E4/E3, E4/E4 phenotypes). Maximum IMT was higher in the apoE4 group than in the apoE3 group (p=0.022). The global atheroma burden index was similarly higher in the apoE4 group than in the apoE3 group (p=0.033). ApoE4 subjects had higher levels of apolipoprotein B (apoB) (p=0.008), triglycerides (p=0.006), remnant lipoprotein-cholesterol (RLP-C) (p=0.023), and lipoprotein(a) [(Lp(a)] (p=0.041) than apoE3 subjects. The mean LDL particle size was smaller in the apoE4 group than in the apoE3 group (p=0.041). CONCLUSIONS: ApoE polymorphism was associated with both carotid and coronary atherosclerosis. Patients with the apoE4 isoform had an increased carotid IMT and a more severe and extensive CAD than patients with the apoE3 isoform.

Attitudes and actions: A survey to assess statin use among Finnish patients with increased risk for cardiovascular events.

BACKGROUND: Statins are the first-line treatment for lowering serum cholesterol and preventing coronary artery disease (CAD). Patients who fail to comply with the prescribed statin treatment face a markedly increased risk for cardiovascular events. OBJECTIVE: The aim of the article was to study the subjective factors, which modulate persistence with and adherence to statin therapy among Finnish patients at high risk for cardiovascular events. METHODS: A total of 1022 Finnish adults diagnosed with CAD, diabetes, hypertension, or severe hereditary dyslipidemia completed an electronic questionnaire survey during a visit in 1 of the 84 community pharmacies participating in the study. RESULTS: Thirty-four percent of the survey respondents were diagnosed with CAD or severe hereditary dyslipidemia and 82% were current or former statin users. Prevalence of nonpersistence with statin therapy was 15% among CAD patients and 17% among respondents without the diagnosis. Most of the nonpersistent statin users had discontinued the medication without consultation of a physician. None of the studied sociodemographic background factors were associated with persistence with statin therapy. Instead, experienced adverse effects, fear of adverse effects, perceived lack of need, and difficulties in use of a statin emerged as powerful predictors of nonpersistence. Awareness of treatment goals was low, and strikingly, public discussion about adverse effects of statins had induced nearly every third discontinuation of statin treatment. CONCLUSION: Several subjective, potentially modifiable reasons for nonpersistence were identified from the patient perspective. Improved utilization of patient-centered approaches in pharmacologic management of cardiovascular risks is necessary to improve adherence, and ultimately, treatment outcomes.

Association of carotid intima-media thickness with angiographic severity and extent of coronary artery disease.

The present study examined the association between carotid intima-media thickness (IMT) and severity and extent of coronary artery disease (CAD). B-mode ultrasound and quantitative coronary angiography were used to assess carotid and coronary artery atherosclerosis in 108 patients with known or suspected CAD who had been referred for cardiac catheterization. Maximum and mean IMT values of carotid arteries were measured and expressed as mean aggregate values. To evaluate anatomic severity and extent of CAD, several quantitative coronary angiographically derived parameters were incorporated into indexes. These quantitative coronary angiographic measurements reflected CAD severity, extent, and overall "atheroma burden" and were calculated for the entire coronary tree and separately for different coronary segments (i.e., left main, proximal, mid, and distal segments). Maximum and mean IMT values were significantly correlated with CAD severity (p = 0.004 and 0.005, respectively), extent (p = 0.022 and 0.016, respectively), and atheroma burden (p = 0.008 for the 2 values). Further, carotid IMT was correlated with quantitative angiographic indexes for mid and distal segments but not with the proximal segments of coronary vessels. In conclusion, our study shows an association between carotid IMT and severity and extent of CAD as assessed by quantitative coronary angiography. Carotid IMT seems to be a weaker predictor of coronary atherosclerosis in the proximal parts of the coronary tree than in the mid and distal parts.

Prasugrel versus clopidogrel in acute coronary syndromes treated with PCI: Effects on clinical outcome according to culprit artery location.

BACKGROUND: Acute coronary syndrome (ACS) mortality increases when the culprit lesion is in the left anterior descending (LAD) artery. We investigated the effects of prasugrel versus clopidogrel according to site of culprit lesion causing ACS treated with percutaneous coronary intervention (PCI) in the TRITON-TIMI 38 study. METHODS: Patients were divided into three groups based on the native coronary artery culprit lesion location. The LAD artery group included also patients with the culprit lesion in the left main (LM) artery. RESULTS: In the whole ACS population, prasugrel recipients had lower rates of the primary endpoint that included cardiovascular (CV) death, non-fatal myocardial infarction (MI) or non-fatal stroke without significant differences across vessel groups. CV death was significantly decreased with prasugrel in the whole ACS population (p=0.03) and in ST-elevation MI (STEMI) patients undergoing primary PCI (p=0.04), with pronounced differences in favour of prasugrel versus clopidogrel when the LAD-LM was the culprit vessel (relative risk reduction 50% in the whole ACS population, 57% in STEMI treated with primary PCI, p for interaction 0.07 and 0.08 respectively). CONCLUSIONS: Prasugrel effects were particularly favourable when LAD-LM was the culprit vessel, resulting in CV mortality reduction in the whole ACS population and in STEMI patients when treated with primary PCI.

Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio Angiogenesis Trial (KAT).

BACKGROUND: Catheter-based intracoronary vascular endothelial growth factor (VEGF) gene transfer is a potential treatment for coronary heart disease. However, only limited data are available about local VEGF gene transfer given during angioplasty (PTCA) and stenting. METHODS AND RESULTS: Patients with coronary heart disease (n=103; Canadian Cardiovascular Society class II to III; mean age, 58+/-6 years) were recruited in this randomized, placebo-controlled, double-blind phase II study. PTCA was performed with standard methods, followed by gene transfer with a perfusion-infusion catheter. Ninety percent of the patients were given stents; 37 patients received VEGF adenovirus (VEGF-Adv, 2x10(10) pfu), 28 patients received VEGF plasmid liposome (VEGF-P/L; 2000 microg of DNA with 2000 microL of DOTMA:DOPE [1:1 wt/wt]), and 38 control patients received Ringer's lactate. Follow-up time was 6 months. Gene transfer to coronary arteries was feasible and well tolerated. The overall clinical restenosis rate was 6%. In quantitative coronary angiography analysis, the minimal lumen diameter and percent of diameter stenosis did not significantly differ between the study groups. However, myocardial perfusion showed a significant improvement in the VEGF-Adv-treated patients after the 6-month follow-up. Some inflammatory responses were transiently present in the VEGF-Adv group, but no increases were detected in the incidences of serious adverse events in any of the study groups. CONCLUSIONS: Gene transfer with VEGF-Adv or VEGF-P/L during PTCA and stenting shows that (1) intracoronary gene transfer can be performed safely (no major gene transfer-related adverse effects were detected), (2) no differences in clinical restenosis rate or minimal lumen diameter were present after the 6-month follow-up, and (3) a significant increase was detected in myocardial perfusion in the VEGF-Adv-treated patients.

Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease.

BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of genes involved in lipid metabolism and inflammation, making it a candidate gene for atherosclerosis and ischemic heart disease (IHD). METHODS AND RESULTS: We investigated the association between the leucine 162 to valine (L162V) polymorphism and a G to C transversion in intron 7 of the PPARalpha gene and progression of atherosclerosis in the Lopid Coronary Angiography Trial (LOCAT), a trial examining the effect of gemfibrozil treatment on progression of atherosclerosis after bypass surgery and on risk of IHD in the second Northwick Park Heart Study (NPHS2), a prospective study of healthy middle-aged men in the United Kingdom. There was no association with plasma lipid concentrations in either study. Both polymorphisms influenced progression of atherosclerosis and risk of IHD. V162 allele carriers had less progression of diffuse atherosclerosis than did L162 allele homozygotes with a similar trend for focal atherosclerosis. Intron 7 C allele carriers had greater progression of atherosclerosis than did G allele homozygotes. The V162 allele attenuated the proatherosclerotic effect of the intron 7 C allele. Homozygotes for the intron 7 C allele had increased risk of IHD, an effect modulated by the L162V polymorphism CONCLUSIONS: The PPARalpha gene affects progression of atherosclerosis and risk of IHD. Absence of association with plasma lipid concentrations suggests that PPARalpha affects atherosclerotic progression directly in the vessel wall.

Progression of atherosclerosis is associated with variation in the alpha1-antitrypsin gene.

OBJECTIVE: Alpha1-Antitrypsin (AAT) protects elastic tissue and may play a role in atherogenesis. The association of atherosclerosis progression with common AAT variants was considered in 2 clinical trials. METHODS AND RESULTS: We examined the association of AAT V213A, S and Z deficiency alleles, and the functional 3' UTR 11478G>A with change in minimal luminal diameter, a measure of focal disease, in the Lopid Coronary Angiography Trial gemfibrozil study of post-bypass men. S or Z carriers (n=14) showed strong progression of disease on placebo (11.5%) but responded well to treatment (3% regression). 11478A carriers treated with placebo or gemfibrozil showed significantly more disease progression (n=8, -14.5% and n=16, -4.0%, respectively) than 11478GG men (n=107, -7.0% and n=108, -1.4%, respectively; overall, P=0.003). VV213 men treated with gemfibrozil (n=68) showed -4.8% progression, whereas A213 carriers (n=55) showed +1.4% regression of disease (P=0.001). No V213A effect was seen on placebo (P=0.11). In the Diabetes Atherosclerosis Intervention Study fenofibrate trial of angiographic progression in type 2 diabetes, the association of 11478A with increased disease progression was confirmed in the treatment group, but not the gemfibrozil-treated A213 association with regression, suggesting a pharmacogenetic difference. CONCLUSIONS: Disease progression is associated with variation in AAT, and low AAT levels promote atherogenesis.

Carotid artery intima-media thickness in Finnish families with familial combined hyperlipidemia.

BACKGROUND: Familial combined hyperlipidemia (FCHL) is the most common hereditary lipid disorder that predisposes the patients to premature coronary heart disease. Members of FCHL families are categorised as affected or unaffected according to serum lipid levels. This study is aimed to evaluate whether there is a difference in carotid artery wall thickness between asymptomatic FCHL family members who are affected and those who are unaffected according to the currently used lipid criteria. METHODS AND RESULTS: Carotid artery ultrasonography with intima-media thickness (IMT) measurements was performed for 148 members of 39 Finnish FCHL families. Study subjects who had no history of coronary heart disease or stroke were divided into two groups according to their serum total cholesterol and/or triglyceride levels. The average carotid IMT of the affected subjects (0.75+/-0.15 mm) was not significantly different from that of their unaffected relatives (0.73+/-0.13 mm), P=0.90. In multivariate analysis, age, gender, and pulse pressure, but no lipid variables, contributed significantly to the variation of carotid IMT. CONCLUSIONS: The IMT findings in FCHL family members indicate that the current lipid criteria alone are of limited value in predicting long-term risk of cardiovascular disease in asymptomatic members of FCHL families.

Serum homocysteine concentrations, gemfibrozil treatment, and progression of coronary atherosclerosis.

The present study aimed to assess the effect of gemfibrozil on serum total homocysteine (tHcy) concentration and to evaluate the influence of tHcy on the angiographically determined progression of coronary atherosclerosis in a randomised, placebo-controlled trial of 395 post-coronary bypass men with low HDL cholesterol levels. The baseline levels of tHcy and those after 16 months of randomised therapy were measured by high-pressure liquid chromatography. Patients were genotyped for the thermolabile variant of N5,N10-methylenetetrahydrofolate reductase (MTHFR) (677C > T substitution). Gemfibrozil therapy was associated with a median 18% increase in tHcy levels (P < 0.01). In the gemfibrozil group increases in tHcy and HDL cholesterol were related (r = 0.217, P = 0.004), but changes in tHcy and triglycerides were not. Levels of tHCy were not associated with baseline extent or progression of coronary-artery disease. Subjects homozygous for the rare MTHFR T allele had 34% higher median tHcy concentrations than CC homozygotes or CT heterozygotes, but responses to gemfibrozil did not differ significantly among genotypes. The MTHFR genotype was not associated with extent or progression of coronary atherosclerosis. We conclude that gemfibrozil causes a significant elevation in tHcy levels, but the clinical relevance of this is unknown at present.

R643G polymorphism in PECAM-1 influences transendothelial migration of monocytes and is associated with progression of CHD and CHD events.

The 643R allele of R643G polymorphism (also known as R670G in the premature protein) in PECAM-1 has been associated with risk of myocardial infarction (MI), while the 643G allele has been associated with risk of coronary artery stenosis (CAS). The aim of this study was to investigate this apparently conflicting association. The association of R643G with risk of MI was determined in the second Northwick Park Heart study (2037 men with 138 CHD events; mean age: 56 years). Smokers homozygous for the 643R allele showed increased risk of MI with a hazard ratio of 2.47 (95% CI: 1.23-4.97; P=0.01) compared to smokers homozygous for the 643G allele. Progression of disease was determined in the Lopid Coronary Angiography Trial (279 men; mean age: 58.9 years). The 643G homozygotes showed greater focal (-0.08 +/- 0.02 mm) and diffuse (-0.01 +/- 0.01 mm) progression of CAS compared to 643R homozygotes (-0.02 +/- 0.02 mm and 0.001 +/- 0.01 mm, respectively; P=0.04). While there was no genotype effect on platelet aggregation, PECAM-1 tyrosine phosphorylation in HUVECs of GG genotype was 2.4-fold greater (P <0.01) than cells of RR genotype, and the level of transendothelial migration of monocytes of GG genotype was greater than that of monocytes of RR genotype following stimulation with either IL-1beta (12% higher, P <0.01) or TNF-alpha (10% higher, P=0.05). These data confirm the association of the R643G polymorphism with MI and CAS and suggest that greater influx of monocytes in individuals homozygous for the 643G may explain the association with CAS.

A novel functional polymorphism in the PECAM-1 gene (53G>A) is associated with progression of atherosclerosis in the LOCAT and REGRESS studies.

A 53G>A polymorphism identified in the 5' untranslated region (5'UTR) of the platelet endothelial cell adhesion molecule-1 (PECAM-1) gene alters a putative shear stress responsive element (SSRE). PECAM-1 was shown to be responsive to shear stress and transient transfection of human umbilical vein endothelial cell (HUVECs) with two luciferase reporter constructs driven by the PECAM-1 promoter and 5'UTR showed a response of the 53G allele, not the 53A allele, to shear stress. Association between the 53G>A, and the previously published L125V polymorphism, and coronary atherosclerosis was examined in two angiographic studies. The frequencies of the rare alleles of the 53G>A and L125V polymorphisms were 0.01 and 0.49, respectively, in the Lopid Coronary Angiography Trial (LOCAT) study and 0.02 and 0.49, respectively, in the Regression Growth Evaluation Statin Study (REGRESS) study. Compared with 53G homozygotes, carriers of the 53A allele showed less focal progression of disease in the LOCAT study and a similar trend in the diffuse progression of disease in the REGRESS study, whereas no association between L125V and coronary atherosclerosis was observed in either study. These data demonstrate that the PECAM-1 gene is responsive to shear stress in vitro and that decreased PECAM-1 gene expression in 53A carriers may influence reduced progression of vessel stenosis in patients with coronary artery disease.

Cardiac adrenergic innervation is affected in asymptomatic subjects with very early stage of coronary artery disease.

UNLABELLED: The aim of this study was to investigate whether, in subjects with a very early stage of coronary artery disease without hemodynamically significant coronary artery stenoses, cardiac adrenergic innervation is already affected. METHODS: Quantitative coronary angiography and dual-isotope SPECT with 123I-metaiodobenzylguanidine (MIBG) and 99mTc-sestamibi (MIBI) were conducted to assess the function of cardiac adrenergic innervation and myocardial perfusion, respectively, in 30 asymptomatic volunteers with a high familial risk for coronary artery disease. Regional quantitative analysis of MIBG uptake and washout rates was performed using the SPECT data from the anteroseptal, lateral, and inferior myocardial regions, which represented vascular supply by the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and right coronary artery (RCA), respectively. RESULTS: The average severity of stenoses was 33% +/- 11% in the LAD, 29% +/- 14% in the LCX, and 26% +/- 19% in the RCA. The severity of stenosis was not related to MIBI uptake in any corresponding myocardial region at rest or during exercise. However, the degree of LAD stenosis correlated directly with delayed MIBG uptake (r = 0.43; P < 0.05) and inversely with MIBG washout (r = -0.34; P = 0.06) of the anteroseptal myocardium. When subjects were divided into tertiles according to the separate severity of stenosis for each coronary artery, delayed MIBG uptake in the anteroseptal region was significantly lower in the lowest LAD tertile (0.34 +/- 0.05) than in the middle (0.41 +/- 0.06; P < 0.01) or highest (0.43 +/- 0.05; P < 0.001) LAD tertile. Correspondingly, delayed MIBG uptake in the lateral region was also lower in the lowest LCX tertile than in the middle tertile (0.34 +/- 0.04 vs. 0.41 +/- 0.06, respectively; P < 0.01). Washout rate was also higher in the lowest LAD tertile (44% +/- 7%) than in the middle (36% +/- 10%; P < 0.05) or highest LAD tertile (34% +/- 8%; P < 0.01). CONCLUSION: The degree of coronary artery stenosis was associated directly with MIBG uptake and inversely with MIBG washout. This finding suggests that the function of cardiac adrenergic nerve endings is modified even in mild coronary artery disease before denervation occurs.