Cardiovascular Longevity: SPRINT Trial Blood Pressure Targets, Statin Science, Lipoprotein(a), and the PAD-Neuropathy Vascular Bridge

When I see a patient with progressive diabetic neuropathy in Howell, I am looking at the cardiovascular system through the peripheral nerve as a window. The small fiber neuropathy that causes burning feet and lost sensation is mechanistically driven by endothelial dysfunction, oxidative stress, and impaired microvascular perfusion — the same biology that drives coronary artery disease, carotid atherosclerosis, and peripheral artery disease. This is not a coincidence. It is a convergence of pathways that makes cardiovascular risk management an integral part of DPN treatment, not a separate specialty concern. In this post, I cover what the highest-quality cardiovascular longevity trials actually say about blood pressure targets, statin therapy, novel lipid risk factors, and the PAD-DPN connection that determines whether a diabetic patient eventually loses a foot.

ASCVD Risk Stratification: The Pooled Cohort Equations and Their Real-World Limitations

The ACC/AHA Pooled Cohort Equations (PCE), introduced in the 2013 Guideline on the Assessment of Cardiovascular Risk (Goff 2014, Circulation; derived from ARIC, CHS, CARDIA, and Framingham cohorts), calculate the 10-year risk of a first atherosclerotic cardiovascular event (MI or fatal coronary heart disease, or fatal/nonfatal stroke) based on age, sex, race, total cholesterol, HDL cholesterol, systolic blood pressure, antihypertensive treatment status, diabetes, and smoking status. Scores above 7.5% typically trigger a statin discussion; scores above 20% indicate high-risk status warranting aggressive risk factor management.

The PCE has meaningful known limitations. It was derived from predominantly middle-aged Black and White American populations — its calibration for Hispanic, Asian, and South Asian patients is poor, consistently overestimating risk in Chinese Americans and underestimating risk in South Asians, who have disproportionate coronary artery disease risk at lower absolute risk scores. The PCE also does not incorporate family history of premature ASCVD (a first-degree relative with ASCVD before age 55 in males or 65 in females is one of the strongest independent risk factors), does not include Lp(a), does not capture coronary artery calcium score, and does not account for chronic kidney disease beyond its contribution to blood pressure. The 2019 AHA/ACC Primary Prevention Guideline explicitly added “risk-enhancing factors” to supplement PCE decision-making — including Lp(a) ≥50 mg/dL, CRP ≥2.0 mg/L, ABI <0.9, and metabolic syndrome — precisely because the PCE alone misclassifies a substantial fraction of intermediate-risk patients.

For my DPN patient population — who carry T2DM as a baseline risk factor — the PCE almost universally places them in the high-risk category without needing additional lipid refinement. This is mechanistically appropriate: T2DM produces an atherogenic dyslipidemia (high triglycerides, low HDL, small dense LDL particles) that is not captured in standard lipid panels, damages endothelial NO production through glucotoxicity, promotes coagulation cascade activation through AGE-RAGE endothelial injury, and activates macrophage foam cell formation through oxidized LDL — four parallel proatherogenic pathways operating simultaneously.

Blood Pressure and Longevity: The SPRINT Trial, J-Curve Controversy, and Optimal Targets

The Systolic Blood Pressure Intervention Trial (SPRINT, Wright et al., NEJM 2015; n=9,361) is one of the most consequential cardiovascular trials of the past decade. Non-diabetic adults with systolic BP ≥130 mmHg and elevated cardiovascular risk were randomized to intensive SBP target (<120 mmHg) vs. standard target (<140 mmHg). The trial was stopped early — after 3.26 years — because the intensive treatment group showed a 25% relative reduction in the primary composite endpoint (MI, other ACS, stroke, HF, or CVD death) and a 27% reduction in all-cause mortality (HR 0.73, 95% CI 0.60–0.90, NNT for all-cause mortality = 61 over 3 years).

The magnitude of the SPRINT benefit placed intensive blood pressure control in the same longevity tier as statin therapy and smoking cessation — among the most impactful individual interventions available in preventive medicine. However, two critical caveats require clinical attention. First, SPRINT excluded patients with diabetes — the ACCORD-BP trial (2010, NEJM; n=4,733 T2DM patients) tested the same <120 vs. <140 mmHg comparison in diabetic patients and found no significant reduction in primary cardiovascular outcomes, only a significant reduction in stroke alone. The 2017 ADA standards accordingly set the BP target for most T2DM patients at <130/80 mmHg rather than the aggressive <120 mmHg target. For my DPN patient population, I target SBP <130 mmHg consistently, recognizing that the renal and vascular protective effects of tight BP control outweigh the modest hypoglycemia risk amplification seen in ACCORD-BP.

The J-curve controversy — the observation that very low diastolic BP (<60–65 mmHg) is associated with increased coronary events in patients with pre-existing coronary artery disease — has been invoked to argue against intensive BP lowering. The mechanistic concern is real: coronary perfusion during diastole depends on diastolic pressure gradient, and patients with significant coronary stenosis may have critically compromised perfusion when diastolic pressure falls below 65 mmHg. However, SPRINT’s intensive group achieved a mean SBP of 121 mmHg with a mean DBP of 68 mmHg — well above the proposed J-curve inflection point. The practical guidance is to monitor both SBP and DBP: target SBP <130 mmHg while maintaining DBP ≥65 mmHg, recognizing that patients with known obstructive CAD may require individualized targets above this threshold.

Antihypertensive Drug Selection for DPN Patients: The ACE/ARB Preference

Drug class selection for antihypertensive therapy in T2DM patients with DPN carries additional mechanistic considerations. ACE inhibitors and ARBs are the first-line agents not merely because of blood pressure reduction but because of direct nephroprotective and vasculoprotective mechanisms: blockade of the renin-angiotensin-aldosterone system (RAAS) reduces glomerular efferent arteriole constriction, lowering intraglomerular pressure and slowing progression of diabetic nephropathy independent of systemic BP effects. HOPE trial (Yusuf 2000, NEJM; n=9,297 high-cardiovascular-risk patients) demonstrated that ramipril reduced cardiovascular death, MI, and stroke by 22% beyond what was expected from BP reduction alone — suggesting direct vascular anti-inflammatory effects. For DPN patients with proteinuria (>300 mg/day), the nephroprotective indication for ACE/ARB is absolute. SGLT2 inhibitors (empagliflozin, dapagliflozin) have emerged as compelling add-on agents not only for glycemic control but for their independent cardiovascular and renal protective effects demonstrated in EMPA-REG OUTCOME, CANVAS, and DAPA-CKD trials — providing another mechanism by which modern diabetes pharmacotherapy bridges glycemic and cardiovascular longevity optimization.

Statin Therapy for Cardiovascular Longevity: Mechanism, JUPITER Trial, and the Peripheral Neuropathy Controversy

Statins — 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors — remain the most evidence-supported pharmacological intervention for cardiovascular longevity in high-risk populations. The Cholesterol Treatment Trialists’ Collaboration meta-analysis (Fulcher 2015, Lancet; 27 trials, n=174,149) established that each 1 mmol/L (39 mg/dL) reduction in LDL-C reduces major vascular events by 22% (RR 0.78) and all-cause mortality by 10% (RR 0.90), with a linear dose-response relationship down to LDL-C levels of 0.5–1.0 mmol/L in high-risk patients. The landmark 4S, CARE, LIPID, HPS, and PROVE-IT trials collectively established statin efficacy across primary and secondary prevention settings.

The JUPITER trial (Ridker et al., NEJM 2008; n=17,802) extended statin evidence into a previously debated population: patients with LDL-C <130 mg/dL but elevated high-sensitivity CRP (hsCRP ≥2.0 mg/L) — a population defined by inflammation rather than hyperlipidemia as the primary risk driver. Rosuvastatin 20 mg/day in this population reduced the primary composite endpoint by 44% (HR 0.56, NNT 95 over 1.9 years, trial stopped early for benefit). JUPITER is important because it demonstrates statin benefit through the anti-inflammatory mechanism (statins reduce hsCRP by 37% independent of LDL lowering) — directly relevant for DPN patients whose neuropathy is partly driven by chronic systemic inflammation.

The statin-peripheral neuropathy question is clinically important and frequently confusing. A 2002 case series (Gaist et al., Neurology) suggested that statins might increase peripheral neuropathy risk, generating considerable patient concern. Subsequent large pharmacoepidemiological studies, including a Danish national registry study (Gaist 2002 re-examined by Nissen 2010) and a meta-analysis of statin RCTs by Rajabally (2010), found no statistically significant increase in polyneuropathy incidence on statin therapy when controlling for T2DM — the primary confounder. For patients with pre-existing DPN: the anti-inflammatory effects of statins (hsCRP reduction, reduced NF-κB activation in vasa nervorum endothelium) likely partially offset whatever direct nerve toxicity case reports have attributed to statin metabolites. The cardiovascular benefit of statins in high-risk DPN patients vastly exceeds any potential neuropathy risk signal — I do not withhold statins from DPN patients based on the neuropathy controversy, but I document the pre-existing neuropathy diagnosis at baseline and monitor symptom change at each visit.

Statin-Associated Muscle Symptoms: Separating Real Myopathy from Nocebo

Statin-associated muscle symptoms (SAMS) — myalgia, weakness, cramps — are the most common reason for statin discontinuation, reported by 7–29% of patients in observational studies. However, the SAMSON trial (Wood 2020, Journal of the American College of Cardiology; n=60, double-blind triple-crossover design) provided the most rigorous quantification of the nocebo contribution: participants received rosuvastatin, placebo, or no pill in rotating 1-month periods. The result: 90% of symptom burden during statin months was also present during placebo months — indicating that the overwhelming majority of statin-attributed muscle symptoms are nocebo effect (expectation of harm producing reported harm) rather than genuine pharmacological toxicity. True rhabdomyolysis (CK >10× upper limit of normal with renal impairment) occurs in approximately 1 in 10,000 treated patients annually. The practical implication for practitioners: a patient who reports severe muscle symptoms on a statin should have CK checked; if CK is normal, a structured rechallenge on a different statin at lower dose with blinded comparison is appropriate rather than immediate discontinuation.

Lipoprotein(a): The Underdiagnosed Risk Factor in 20% of the Population

Lipoprotein(a) — Lp(a) — is a modified LDL particle with an additional apolipoprotein(a) attached via a disulfide bond. Unlike LDL, which responds significantly to dietary fat modification and statin therapy, Lp(a) levels are 70–90% genetically determined (primarily by variations in the LPA gene encoding apolipoprotein(a)), change little with lifestyle interventions, and are reduced only modestly (20–30%) by PCSK9 inhibitors and not at all by statins. Elevated Lp(a) (typically defined as ≥50 mg/dL or ≥125 nmol/L) is present in approximately 20% of the global population and is associated with a 2–3-fold increase in cardiovascular events in population studies independent of LDL-C level.

The 2019 European Atherosclerosis Society consensus statement and the 2022 ACC Expert Consensus on Lp(a) both recommend that every adult be tested for Lp(a) at least once in a lifetime — yet a 2023 survey found that fewer than 10% of primary care providers routinely order Lp(a) testing. This is a significant gap in cardiovascular longevity medicine. For my DPN patients with “well-controlled” traditional risk factors who nevertheless progress to cardiovascular events or PAD, Lp(a) elevation is frequently the undetected driver. Mechanistically, Lp(a) carries oxidized phospholipids (OxPL) that promote macrophage foam cell formation even at LDL-C levels that appear normal, interferes with fibrinolysis by competing with plasminogen for binding sites, and promotes aortic valve calcification through mechanisms distinct from LDL.

The therapeutic landscape for Lp(a) is evolving rapidly. Two RNA-based therapies — pelacarsen (antisense oligonucleotide, Novartis) and olpasiran (siRNA, Amgen) — have demonstrated Lp(a) reductions of 80–95% in Phase 2 trials and are in Phase 3 cardiovascular outcomes trials (Lp(a)HORIZON and OCEAN[a]-OUTCOMES respectively). These agents represent the first genuinely Lp(a)-specific therapies and are expected to establish Lp(a)-lowering as a causal cardiovascular intervention within the next 2–3 years. For current management of identified high Lp(a) patients: optimize all other risk factors aggressively (achieving lower LDL-C targets than standard guidelines recommend may partially offset Lp(a) risk), consider PCSK9 inhibitor for partial Lp(a) reduction if LDL is also elevated, and refer to a lipidologist or preventive cardiology specialist for integration into the emerging RNA therapy pipeline.

Coronary Artery Calcium Scoring: The Longevity Decision Tool That Reclassifies Risk

Coronary artery calcium (CAC) scoring by non-contrast CT is the best-validated tool for reclassifying intermediate-risk patients (PCE 5–20% 10-year risk) into higher or lower actual risk categories. The Multi-Ethnic Study of Atherosclerosis (MESA, n=6,814; Detrano 2008, NEJM) established that a CAC score of 0 identifies patients with very low near-term cardiovascular risk regardless of calculated PCE score — a finding so robust that the 2019 AHA/ACC guideline specifically endorses CAC = 0 as grounds for withholding statin therapy in intermediate-risk patients who are otherwise hesitant. The MESA 10-year event rates by CAC category: CAC 0 → 0.4% annual event rate; CAC 1–100 → 0.9%; CAC 101–400 → 1.7%; CAC >400 → 2.8% annual event rate.

For the DPN patient population, CAC scoring serves a specific clinical role: it identifies subclinical atherosclerosis that may not manifest as angina or claudication symptoms yet but directly indicates the vascular disease burden that threatens the microvasculature feeding peripheral nerves and foot tissues. A DPN patient with a CAC score >400 has documented macrovascular calcification that predicts accelerated progression of both cardiovascular events and microvascular complications — motivating more aggressive intervention across blood pressure, lipids, glucose, and lifestyle domains simultaneously. The radiation dose of CAC CT is approximately 1–2 mSv (comparable to a mammogram), and the cost is typically $100–150 without insurance in most US markets — making it one of the most cost-effective longevity assessments available.

Peripheral Artery Disease and Diabetic Neuropathy: The Vascular Bridge

Peripheral artery disease (PAD) and diabetic peripheral neuropathy are the two most common comorbidities in patients presenting to my practice with foot complications, and their coexistence dramatically amplifies amputation risk. PAD is defined as resting ankle-brachial index (ABI) <0.90 and is present in approximately 20–30% of T2DM patients, though the true prevalence is higher because medial arterial calcification in long-standing diabetes can falsely elevate ABI readings, causing apparent normalization of severely stenotic vessels. The toe-brachial index (TBI <0.70) and transcutaneous oxygen pressure (TcO₂ <40 mmHg) are more reliable hemodynamic assessments in calcified diabetic arteries.

The convergence of PAD and DPN — termed “neuroischemic” diabetic foot disease — is the highest-risk phenotype in diabetic foot care. PAD impairs wound healing by reducing oxygen and nutrient delivery to tissues; DPN impairs pain sensation, removing the protective warning signal that prevents repetitive injury; together they create a foot that gets injured without warning and cannot heal. The International Working Group on the Diabetic Foot (IWGDF) classifies wound outcomes by the WIfI (Wound, Ischemia, foot Infection) scoring system, in which ischemia severity is the strongest predictor of amputation at 1 year — outweighing wound size and infection severity combined.

From a cardiovascular longevity perspective, PAD is also a powerful independent predictor of all-cause mortality: patients with ABI <0.90 have a 3–6-fold increased mortality risk over 10 years compared to those with normal ABI, driven by concomitant coronary and carotid atherosclerosis (CAPRIE, EURODIALE studies). The PREDIMED secondary PAD analysis mentioned in our Mediterranean diet post (66% PAD risk reduction with Mediterranean diet) demonstrates that the same dietary pattern protecting the heart also protects the peripheral vasculature — providing another mechanism by which dietary longevity interventions directly benefit the DPN population. For PAD patients, statin therapy is independently indicated regardless of baseline LDL: the HEART trial and REACH registry both demonstrated that statins reduce cardiovascular mortality in PAD patients and also reduce the rate of critical limb ischemia and amputation in the most severe PAD cases.

Cardiovascular Longevity Optimization Protocol for DPN Patients

The following protocol represents the cardiovascular longevity framework I apply at Balance Foot & Ankle for every DPN patient, recognizing that peripheral nerve health is downstream of vascular health and that the same interventions that extend lifespan also reduce amputation risk.

Baseline Assessment (Every New DPN Patient)

Vascular: Bilateral resting ABI (if >1.3, proceed to TBI). If ABI <0.9 or TBI <0.70, urgent vascular surgery referral before any wound procedures. Lipids: Full fasting lipid panel + Lp(a) (one-time lifetime test if never done) + hsCRP. Calculate non-HDL-C (total cholesterol minus HDL) as the more reliable atherosclerotic particle burden metric than LDL alone in T2DM patients with hypertriglyceridemia. Blood pressure: Office BP with proper technique (patient seated 5 minutes, arm supported at heart level, averaged over 2 readings). Target SBP <130 mmHg for T2DM patients per 2017 ADA guidelines. Glucose: Fasting glucose + HbA1c + fasting insulin (to calculate HOMA-IR and quantify insulin resistance beyond glycemic control). 10-year ASCVD risk: PCE calculation, supplemented with Lp(a), hsCRP, ABI, family history, and CAC score (if available or indicated) per 2019 ACC/AHA guidelines.

Treatment Targets and Intervention Thresholds

LDL-C targets (T2DM with DPN = “high risk” by default): LDL-C <70 mg/dL for high-risk; <55 mg/dL for very-high-risk (established ASCVD or PAD). If LDL-C >70 mg/dL on maximum tolerated statin, add ezetimibe (further 18–24% LDL reduction); if still above target, add PCSK9 inhibitor (50–60% additional LDL reduction). Triglycerides: <150 mg/dL fasting; if >500 mg/dL (pancreatitis risk), fibrates or high-dose omega-3s first; if 150–500 mg/dL on maximally treated LDL, consider pharmaceutical EPA (Vascepa 4g/day) per REDUCE-IT indication. Blood pressure: <130/80 mmHg for T2DM; first-line ACE inhibitor or ARB (nephroprotection + cardiovascular benefit beyond BP effect); add amlodipine or thiazide if needed to reach target. HbA1c: <7.0% for most T2DM patients; however, for DPN specifically, the evidence for intensive glycemic control (UKPDS-derived) shows that the greatest neuropathy benefit occurs in the first 5–10 years of T2DM — by the time DPN is established, aggressive HbA1c reduction produces diminishing nerve benefit while increasing hypoglycemia risk.

Annual Surveillance: The 5-Minute Cardiovascular Longevity Check

At every annual DPN visit: repeat bilateral ABI (any decrease of >0.15 from baseline suggests hemodynamic deterioration requiring vascular referral); update fasting lipid panel and HbA1c; measure both arms for BP discordance (bilateral BP difference >15 mmHg suggests subclavian stenosis); document foot perfusion clinically (capillary refill time >3 seconds, absent pedal pulses, dependent rubor, pallor on elevation); review statin adherence and document hsCRP trajectory (statin adequacy correlates with hsCRP reduction to <1.0 mg/L). For patients with established PAD: vascular surgery co-management with surveillance duplex ultrasound of tibial vessels annually, TcO₂ measurement at any new foot wound before initiating wound care.

Frequently Asked Questions

Should I aim for systolic blood pressure below 120 if I have diabetes?

The SPRINT <120 mmHg target applies to non-diabetic high-risk patients. For T2DM, the ACCORD-BP trial tested the same comparison and found no significant reduction in the primary composite cardiovascular outcome — though stroke was reduced significantly. The 2017 ADA Standards of Medical Care and 2019 ACC/AHA guideline both recommend <130/80 mmHg as the target for most T2DM patients. I use <130 mmHg SBP as my clinical target for DPN patients, with individualization for frail elderly patients where orthostatic hypotension from aggressive BP lowering creates fall risk — a particularly serious concern in patients whose peripheral neuropathy already impairs balance and proprioception.

Do statins cause or worsen diabetic neuropathy?

The evidence does not support withholding statins from DPN patients based on neuropathy concerns. The early case-series suggestion of statin-induced neuropathy (Gaist 2002) has not been replicated in large pharmacoepidemiological studies when T2DM is properly controlled for as a confounder. More importantly, statins reduce vascular inflammation (hsCRP) and may protect the vasa nervorum — the tiny blood vessels that supply peripheral nerves — through anti-inflammatory mechanisms. The cardiovascular benefit in high-risk DPN patients (30–40% relative reduction in major cardiovascular events over 5 years) enormously outweighs any theoretical neuropathy risk. I document baseline neuropathy severity at statin initiation and reassess at 6 months; significant symptom progression warrants CK measurement and rheumatologic evaluation, but I do not attribute neuropathy worsening to statins absent specific evidence.

What is the ankle-brachial index and why does it matter for my neuropathy?

The ankle-brachial index (ABI) is the ratio of the systolic blood pressure at the ankle to that at the brachial artery. A normal ABI is 0.91–1.30; values below 0.90 indicate peripheral artery disease. The ABI matters for neuropathy because the combination of PAD and DPN — called neuroischemic diabetic foot — is the highest-risk scenario for diabetic foot complications and amputation. With DPN alone, neuropathic wounds can heal if blood supply is intact. With PAD alone, wounds are slow to heal but pain typically prompts medical attention. With both: wounds form silently (no pain), don’t heal (inadequate perfusion), and can progress to deep infection and amputation without the patient feeling sufficient urgency to seek care. ABI screening at your initial neuropathy evaluation is essential — not optional — for this reason.

Should I get my Lp(a) tested, and what can I do if it’s high?

Yes — the European Atherosclerosis Society and ACC both recommend that every adult have Lp(a) measured at least once. It is particularly important if you have a family history of premature heart disease, have had a cardiovascular event despite “normal” cholesterol levels, or are in an intermediate-risk PCE category where you’re unsure about statin therapy. If Lp(a) is elevated (>50 mg/dL), the current management is: optimize all other modifiable risk factors aggressively (achieving LDL-C <55 mg/dL is reasonable), consider PCSK9 inhibitor if LDL is also elevated (modest Lp(a) reduction as secondary benefit), and monitor closely for cardiovascular events with regular follow-up. Two RNA-based drugs in Phase 3 trials — pelacarsen and olpasiran — may reduce Lp(a) by 80–95% and are expected to reach the market within the next few years, transforming management of elevated Lp(a).

I was told my cholesterol is “fine” but I still have significant neuropathy. Could vascular factors be driving my neuropathy beyond what my cholesterol shows?

Absolutely. “Normal cholesterol” in a standard lipid panel captures LDL, HDL, and total cholesterol — it does not capture: Lp(a) (elevated in 20% of the population, not on any standard panel); small dense LDL particle count (the most atherogenic LDL fraction, elevated in diabetic dyslipidemia despite “normal” calculated LDL); hsCRP (inflammatory burden on vasa nervorum); ABI (peripheral vascular perfusion to the nerve microvasculature); or coronary calcium score (total atherosclerotic burden). DPN worsening despite “controlled” traditional risk factors frequently reflects one or more of these under-assessed pathways. A comprehensive cardiovascular longevity evaluation — not just a standard lipid panel — is what the evidence supports in this population.

Bottom Line

Cardiovascular risk management is not a separate domain from diabetic neuropathy care — it is the vascular framework within which every neuropathy intervention either succeeds or fails. The SPRINT trial established that targeting SBP <120 mmHg (in non-diabetic high-risk patients) reduces all-cause mortality by 27% — evidence strong enough to change guidelines globally. Statins provide 22% event reduction per 1 mmol/L LDL reduction across the risk spectrum, and their anti-inflammatory effects may directly protect the vasa nervorum feeding peripheral nerves. Lp(a) — elevated in 20% of all adults — remains systematically undertested despite being a causally validated cardiovascular risk factor with RNA therapies in late-stage trials. Coronary calcium scoring is the best current tool for reclassifying intermediate-risk patients. And the ABI is the single most consequential screening test for the neuroischemic foot that neither the patient nor their primary care physician may recognize until a wound fails to heal.

Sources

• Wright JT Jr, et al. A randomized trial of intensive versus standard blood-pressure control (SPRINT). N Engl J Med. 2015;373(22):2103–2116.
• ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus (ACCORD-BP). N Engl J Med. 2010;362(17):1575–1585.
• Ridker PM, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein (JUPITER). N Engl J Med. 2008;359(21):2195–2207.
• Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis. Lancet. 2015;385(9976):1397–1405.
• Wood FA, et al. N-of-1 trial of a statin, placebo, or no treatment to assess side effects (SAMSON). J Am Coll Cardiol. 2020;76(17):1887–1897.
• Detrano R, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups (MESA). N Engl J Med. 2008;358(13):1336–1345.
• Nordestgaard BG, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844–2853.
• Bhatt DL, et al. Cardiovascular risk reduction with icosapentaenoic acid (REDUCE-IT). N Engl J Med. 2019;380(1):11–22.
• Yusuf S, et al. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events (HOPE). N Engl J Med. 2000;342(3):145–153.
• Goff DC Jr, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk. Circulation. 2014;129(25 Suppl 2):S49–73.

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