Cardiovascular disease is a taking cause of morbidity and mortality. Is responsible for more than 17 million deceases worldwide every twelvemonth 31 of entire mortality, while in Europe this per centum rises up to 42 % ( 1,2 ) . It ‘s a chronic upset and normally by the clip that symptoms occurred it ‘s in advanced phase. CV disease is strongly related to life manner ( smoke, physical inaction, unhealthy diet wonts and emphasis ) ( 3 ) every bit good as with several hazard factors such as high blood pressure, diabetes, dyslipidaemia, fleshiness, and other conditions that present increased CV morbidity and mortality and tacked into consideration such as age, household history of premature coronary bosom disease and endothelial disfunction ( 2 ) . Prevention and confrontation of these hazard factors represents the basis of CVD intervention. Normally, different hazard factors are presented in the same patient. Although high blood pressure represents likely the most of import and frequent hazard factor, merely 23 % of those patients is free from extra hazard factors ( 4 ) . The bulk of patients present overlapping hazard factors ( 4 ) . The coexistence of different hazard factors increases exponentially the hazard for CV morbidity and mortality. This phenomenon is good represented in patients with metabolic syndrome since they present a bunch of different hazard factors were the hazard of CVD is greater than the amount of its single constituents ( 5,6 ) . This led the Scientific Community to present the term of entire ( or planetary ) CV hazard factor with the intent to measure and pull off all the hazard factors that every patient presents. This was accomplished with the debut of different theoretical accounts, tonss or charts that practically estimates the CV hazard of every patient under probe. The European Society of Hypertension use a theoretical account that takes into consideration the degree of blood force per unit area, the presence of different hazard factors, Diabetes, diagnostic Cardiovascular disease and mark organ harm, in order to sort those patients in to low, moderate, high and really high hazard harmonizing their opportunity to hold a CV event over 10 old ages ( 7 ) Fig 1.

Classical Hazard factors

Although pulse force per unit area, unnatural glucose tolerance trial and diabetes mellitus, metabolic syndrome, fleshiness and clogging slumber apnea are established risk factors impacting CV morbidity and mortality, are discussed in other chapters of this manual. All classical hazard factors portions common tracts advancing oxidative and mechanical emphasis redness bring oning endothelial disfunction, atherogenesis and atherothrombosis taking to weave hurt and CV disease with increased morbidity and mortality ( Fig 2 ) .


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There is overpowering grounds showing the cardiovascular jeopardies of smoke or inactive smoke and the benefits obtained with smoking surcease. Smoking practically triggers the atherogenic cascade through the activation of endogenous beginning of free groups ( Xanthine oxidace, uncoupled NOS, NADPH oxidace ) or other oxidizers that

coffin nail fume contains in copiousness ( 8 ) . Furthermore promotes the inflammatory response ( indispensable constituent for the induction and patterned advance of coronary artery disease ) , bring oning vasomotor and endothelial disfunction, smooth musculus proliferation, thrombocyte and thrombohemostatic disfunction taking to atherogenesis ( 8 ) . Smoking and inactive smoke modificates the lipid profile. Increases oxidative alteration of LDL ( 9 ) , decreases plasma high lipoprotein degrees ( HDL ) and alters the HDL/LDL, HDL and entire cholesterin every bit good as HDL/triglycerides ratios ( 10,11 ) . Furthermore, smoking induces disconnected additions of blood force per unit area every bit good as bosom rate and stimulates sympathetic activity ( 12,13 ) . Smoking surcease lessening significantly the hazard of CV morbidity and mortality and within 10-15 old ages the hazard attack that of ne’er tobacco users ( 2 ) .


In the Framingham survey cholesterin every bit good as lipoproteins ( LDL, HDL ) are proven to be first-class forecasters of cardiovascular morbidity and mortality ( 14 ) . Harmonizing this survey, for every 1 % addition of plasma cholesterin the hazard of coronary disease rose from 2 to 3 % while for every 1 % lessening of cholesterin, there was a 2 % lessening of hazard for coronary disease. The construct of lipid take downing scheme is good known since several surveies proved the benefits obtained from the control of lipid profile. Reducing LDL cholesterin more than 50 % , seems to halt the patterned advance or even taking to arrested development of coronary coronary artery disease ( 15 ) . In patients with type 2 diabetes, take downing of LDL by 2-3 mmol/L with statin therapy, reduced the 5 twelvemonth incidence for bosom onslaught, revascularization and ischemic shot for about 40-50 % ( 16 ) . The benefit of LDL take downing scheme was important besides to non diabetic patients ( 16 ) . In primary bar ( Jupiter test ) , patients that reached LDL & A ; lt ; 2.0 mmol/L had the lowest One hundred five event rate ( 17 ) . Participants randomized to rosuvastatin and achieved LDL cholesterin less than 1.8 mmol/L in comparing to placebo showed a 55 % decrease in vascular events ( 17 ) . High blood pressure and dyslipidaemia often coexists. About 52 % of dyslipidemics suffers besides from high blood pressure ( 18 ) . The prevalence of combined high blood pressure and dyslipidaemia is increased in patients with diabetes mellitus ( 41 % ) , with metabolic syndrome ( 37 % ) , and in patients with ego reported cardiovascular disease ( 44 % ) ( 19 ) . This combination is more frequent in hypertensives than in normotensives topics ( 20 ) . Harmonizing the ESC guidelines, the primary end is to accomplish mark LDL degrees harmonizing the entire CV hazard with all agencies ( lifestyle alterations or lipid take downing agents ) , independently the usage or non of lipid take downing agents in order to diminish CV morbidity and mortality ( 2 ) .

Kidney Injury

Kidney disease is a universe broad public wellness job with increased morbidity and mortality. The definition of kidney disease is based on the presence of A ) anatomical or structural constituent ( markers of kidney harm, including proteinuria ) , ( B ) functional constituent ( based on GFR ) , and ( C ) a temporal constituent ( at least 3 months ‘ continuance of structural and/or functional changes ) ( 21 ) .

Its association with increased CV events is good known from 4 decennaries ( 22 ) . Evidence for this association was foremost recognized in dialysis patients were the incidence of CV decease was highly high ( 23,24 ) . Patients with end phase nephritic disease ( ESRD ) showed 15 to 30 creases higher CV mortality than general population ( 23 ) and the per centum of decease in this population reached about the 50 % ( 23 ) . However farther surveies, showed the magnitude of the job since the presence of even minor nephritic disfunction ( expressed by the lessening of Glomerular Filtration Rate ( GFR ) and/or hint of microalbuminuria or albuminuria ) increase the hazard for CV events. The Joint National Committee ( JNC-7 ) every bit good as the European Society of Hypertension-European Society of Cardiology ( ESH-ESC ) recognized as hazard factors the estimated GFR ( eGFR ) value & A ; lt ; 60 ml/min per 1.73 M2 and microalbuminuria. ( 25,7 ) . There are several surveies confirming that these two factors have a major impact on CV events. In low hazard patients, a survey enrolled more than 1 million patients, was observed and independent graded association between eGFR and the hazard of CV events, foregrounding the clinical and public importance of nephritic damage ( 26 ) .

One in 13 hypertensive patients advancement to hypercreatininemia every twelvemonth ( 27 ) .In patients with high blood pressure, informations from HOT test showed that patients with eGFR & A ; lt ; 60 ml/min per 1.73 M2 presented about dual CV events in comparing with patients with eGFR & A ; gt ; 60 ml/min per 1.73 M2 ( 28 ) . In LIFE survey, microalbuminuria was associated with increased CV events while during follow up, topics with lowest One hundred five events rates, presented a grater decrease of microalbuminurua after intervention. ( 29 ) .In the Hoorn survey, the comparative hazard of a CV decease increased by 26 % per 5 mL/min/1.73m2 lower GFR. ( 30 ) . Sing high hazard patients, the HOPE test showed a important association between CV event and serum creatinine concentration. Patients with serum creatinine from 1.4 to 2.0 showed a higher jeopardy ratio ( HR ) by 40 % , the presence of microalbuminuria increased the HR by 59 % , and presence of both increased the HR by 108 % ( 31 ) . In bosom failure patients, informations from the PRIME II survey showed that baseline GFR was a important forecaster of CV mortality, stronger and independent than impaired expulsion fraction or NYHA category ( 32 ) .

Patients with impaired nephritic map normally present multiple carbon monoxide morbidities and hazard factors. Those patients present accelerated atherosclerotic disease, while the presence of diabetes or high blood pressure can be the cause or the effect ( for the last 1 ) taking to an increased hazard for CV morbidity and mortality. In add-on, there is an activation of sympathetic nervous system with increased catecholamine turnover taking to increased CV events ( 33 ) .Moreover, declining of kidney disease is associated with alterations in lipid profiles with increased oxidization of LDL, increased degrees of triglycerides and lessening degrees of HDL taking to dyslipidaemia ( 34 ) . Kidney disease is associated with endothelial disfunction were microalbuminuria besides reflects this damage ( 35 ) .

Although there is overpowering grounds tie ining nephritic impairement to increased CV hazard there are besides some concerns. In clinical pattern, creatinine clearance is measured with 24-h urine aggregation. GFR can be estimated from serum creatinine degrees utilizing anticipation equations like Cockroft-Gault or Modification of Renal Disease ( MDRD ) , that take age, sex, race, and organic structure weight into history. However, MDRD expression underestimates true GFR above 60 ml/min/1.73 M2 ( 36 ) while Cockroft-Gault equation overestimations measured GFR in people with normal nephritic map ( 37 ) . Recent meta analysis look intoing several blood force per unit area degree marks in patients with CKD failed to show definite benefits in footings of renal or CV results ( 38,39 ) . Finally, it ‘s unsure if the decrease of proteinuria at least in persons without markedly reduced GFR improves clinical results ( 40-42 ) .

Sympathetic activity

The sympathetic nervous system ( SNS ) plays a important function in cardiovascular homeostasis. Exerts long term circulatory control and affects regional blood flow nevertheless, inappropriate activation additions cardiovascular morbidity and mortality ( 43 ) .

SNS activity is more marked in patients with arterial high blood pressure, kidney disease, fleshiness, metabolic syndrome and sleep apnea syndrome. SNS overactivity holds besides a cardinal physiopathological function in bosom failure, acute coronary syndromes and arrhythmias ( 44-47 ) . Sympathetic overactivity can be the cause or the effect of these conditions and the trigger consequence can non be easy distinguished. Inhibition of sympathetic overactivity by assorted agencies, including cardinal SNS suppressing drugs, peripheral alpha- and beta- sympathomimetic receptor blockers, or fresh attacks as nephritic sympathetic denervation have been used successfully in the intervention of all these upsets. In 1940s ganglionic barricading drugs were used as options to sympathectomy ( 48 ) and becomes the first effectual antihypertensive drug cluss ( 49 ) . Subsequently and until the epoch of suppression of the rennin-angiotensin-aldosterone system ( RAAS ) , primary intervention of high blood pressure was based on cardinal sympathetic inhibitors clonidine, Raudixin and alpha alpha methyl dopa, followed by the alpha and beta adrenergic receptor ( AR ) blockers ( 49 ) . The outgrowth of newer antihypertensive drugs placed the cardinal moving drugs to the out of boundss nevertheless there are several conditions were therapy lessening besides sympathetic activity with an extra benefit since SNA plays an of import function in the development and the patterned advance of the diseases mentioned supra. Although grounds refering the benefits of alpha blockers and cardinal playing agents are limited seems to hold favourable metabolic effects and diminish blood force per unit area adequately ( 50 ) nevertheless they do n’t stand for the 1st pick for antihypertensive intervention. B blockers blocks alpha and beta adrenoreceptors ( depends from cardioselectivity ) modulating sympathetic activity ( 51 ) . In high blood pressure are used entirely or in combination cut downing CV morbidity and mortality. In a meta analysis that included STOP high blood pressure -2 ( water pills or b-blockers vs. ACE-inhibitors vs. dihydropiridine Ca channel blockers ) , ( UKPDS ) ( atenolol vs. Capoten ) , NORDIL ( thiazide or b-blocker vs. diltizem ) and ( CAPP ( water pills or b-blockers vs. Capoten ) B blockers offered similar CV protection when compared with ACE inhibitors, water pills or Ca channel blockers ( 52 ) . Furthermore, B blockers are used in a assortment of diseases ( Ischemic bosom disease, Heart failure, Arrhythmias ) diminishing CV morbidity and mortality ( 51 ) . The lessening of sympathetic activity is used besides in other curative patterns like nephritic denervation and carotid baroreceptor stimulation diminishing blood force per unit area in those patients. In the simpleness HTN-1 and HTN-2 survey, nephritic denervation decreased significantly blood force per unit area in patients with immune high blood pressure showing the important function of sympathetic activity in high blood pressure ( 53,54 ) . Carotid baroreceptor stimulation besides decreases sympathetic activity with sustained alterations on blood force per unit area and bosom rate variableness. Several surveies induced in patients with immune high blood pressure showed the good consequence of this method diminishing sympathetic activity nevertheless farther surveies are needed to show the good consequence beyond blood force per unit area control of these methods ( 55,56 ) .

SNA can be decreased besides not invasively utilizing devices like rhinal C-Pap in patients with Obstractive Sleep Apnea ( OSA ) . Several surveies showed that the usage of nC-PAP lessening sympathetic activity every bit good as blood force per unit area ( 57-60 ) . In a survey enrolled more that 1500 patients with OSA and followed up for about 10 old ages, the usage of rhinal cPAP decreased significantly the hazard of CV events in patients with terrible OSA ( 60 ) . The lessening of CV events are attributed besides to the lessening of redness and endothelial disfunction were nevertheless SNA plays a important function ( 59 ) .

Hazard factors and concerns

In general, hazard factors non merely hold to turn out their predictive importance, they must hold an habit-forming value and better the truth to quantify future CV events.

C reactive protein ( CRP ) is considered as an of import inflammatory hazard factor, associated with increased CV morbidity and mortality ( 61 ) .Jupiter test provided grounds for the stableness of hsCRP over the clip on moth to moth or twelvemonth to twelvemonth footing similar to that of LDLc fact that has been observed besides in other surveies ( 17,62,63 ) . In add-on Jupiter test showed that low on intervention degrees of hsCRP is associated with better clinical result ( 17 ) . In a bomber survey o LIFE test, hsCRP had a important predictive value but it was n’t independent from urine albumin/creatinine ratio ( 29 ) . However, there are several concerns. In the Framingham survey ( 64 ) , CRP and other inflammatory markers did n’t showed a considerable betterment in the appraisal of entire CV hazard. In general this hazard factor seems to hold low specificity, is dearly-won ( compared with others biological hazard factors ) , does n’t hold any specific agents ( aiming CRP ) that lessening CV events and have many confounders ( 2 ) .

Harmonizing to National Academy of Clinical Biochemistry hsCRP appraisal should be done in patients with metabolically stable province, free of infection or ague unwellness, while hsCRP measuring might be utile for farther stratification into a higher or lower hazard class in intermediate hazard patients ( 10 % -20 % ) with uncertainness as to the usage of preventative therapies such as lipid-lowering medicines or acetylsalicylic acid ( 65 )

Homocystein is a marker of endothelial map and oxidant emphasis. Several surveies associate increased degrees of homocystein with increased CV events ( 66 ) . However, there are several confounder parametric quantities ( lifestyle, metabolic, nutritionary ) ( 2 ) . Furthermore, there are several causes that can increase homocystein like vitamin lack ( B12, B6, folic acid ) , the usage of certain medicines, impaired nephritic map and smoke ( 67-69 ) .


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